Time out for a bit of infectious disease terminology. The words pathogenic, virulent and transmissible get tossed around a lot when talking about the bird flu virus and the possibilities of a pandemic. They are sometimes used interchangeably. They aren't interchangeable, however, and their differences are important to understanding talk about bird flu.
Let's start with one other term, the pre-requisite for the other three, infectivity. Viruses are bits of genetic material and associated proteins that do essentially one thing and one thing only: make copies of themselves. That's it. They aren't even capable of doing that on their own. They need to hijack the machinery of a living organism's own reproductive capacity to make their self-copies. They do this by infecting some host cell, that is, getting into the cell of an organism and taking over its cell reproduction workshop which the virus then uses to make copies of itself. Each virus has particular organisms and cells in that organism it uses for this. the organisms (animal, plant, bacteria) it can do this in is called its host range. If the host has a lot of different kinds of cells and tissues (as humans do), it is usual for the virus to restrict itself to one or a few types of cells. In humans, for example, the influenza virus seems to infect mainly cells within the respiratory tract and only some of the cells, at that. The ability to replicate within a host cell is called infection.
If cells can be infected it doesn't mean the host will suffer for it, however. Some viruses can infect cells without apparent harm to the host. On the other hand, we also know that infecting cells can be bad for the host and if the interruption in host structure and function is sufficiently great, the host becomes sick (diseased). Pathogenicity is the ability of a virus to cause disease in a host it infects. Usually whether the host suffers from infection is also modulated by the state of the host's health, age and factors in the environment. Pathogenicity (the ability to cause disease) is thus not something inherent in the virus but a combination of virus, host and environment.
The sickness or disease the infection causes can be mild to really bad. Virulence is the ability of a pathogenic virus to cause really bad disease. Influenza A/H5N1 and the common cold both cause disease. H5N1 is virulent, a cold virus is not. Thus pathogenicity and virulence are not the same thing. Virulent viruses are pathogenic but not necessarily the reverse. Pathogenic viruses need not be virulent if they don't cause serious disease.
What about H5N1, then, also designated a Highly Pathogenic Avian Influenza virus (HPAI). This is accepted terminology and refers to the fact that most influenza viruses are not very virulent in birds. If they are virulent, killing the birds in short order, they are designated HPAI. Doesn't this contradict the terminology we just set out? Shouldn't they be called Highly Virulent Avian Influenza viruses? Yes. So sue me. Or rather sue whoever it was that misnamed them. If they had read this post, they'd have called them HVAI instead of HPAI.
Finally, pathogenicity is not the same as transmissibility. Transmissibility refers to the ability to pass from one person to another. Rabies virus is a virulent pathogen, but it transmissible from person to person. The common cold is transmissible (or better, easily transmissible) and pathogenic but not virulent. H5N1 so far is not very transmissible from person to person but is easily transmissible from bird to bird and is virulent for both (and of course, pathogenic for both).
Why is the terminology important? It is important only because it refers to distinct biological phenomena. Infectivity, pathogenicity, virulence and transmissibility all have their own determinants. While we know what some of these determinants are, we still haven't been able to put all the pieces together into a coherent and satisfying picture. The more we learn with our powerful new tools of molecular biology, the less we seem to know, if we use as a reference what we thought we once knew. It's not all in the sequences for a virus, any more than understanding human biology ended with specifying the human genome. There is a great deal of truly elegant and important work being done at the virology bench. We can hope that soon, infectivity, pathogenicity, virulence and transmissibility will be better understood.
But our success in weathering a pandemic, should one occur, will still come down to the social structures we employ to manage its consequences.
Thanks for this. I will definitely be stealing it for my 'Influenza 101' presentations.
(BTW, in the paragraph about transmissibility, check the sentence about Rabies.)
Here's an RSS question in relation to the transition to this new (cool) blogging site:
Is there an RSS feed with the full-text of the Reveres' posts? It's a small thing, but it's so much nicer being able to read the full post from the confines of my feed-reading program instead of always having to open a new browser window/tab.
Thanks, Revere, I'm clearer about this except for one aspect:
"Pathogenicity is the ability of a virus to cause disease in a host it infects."
So what distinguishes different degrees of pathogenicity or *ability* to cause disease if it's not virulence (i.e. how bad it makes you feel). Is *ability* tied to something like the extent of viral load required to cause disease, or are you saying that pathogenicity is simply an on/off characteristic and that the entire idea of high-low pathogenicity is therefore invalid.
I also don't quite get the idea of host/virus/environment in pathogenicity. You're not suggesting that if I'm "run down" and/or chilled, and I get sicker than expected as a result, that we say my virus was more pathogenic?
Thanks for the post Revere - a lot of us reading the blog may be semi educated in other areas but know squat about biology and is relevant sub-disciplines. Could you clarify one point resspecting transmissibility? I seem to remember something (I think on Dr. Nimans site) to the effect that there is some sort of systematic framwork within which bio types decide epidemic risk. I want to say there is some sort of number assignment (of 2, 3 , etc.)and if an infected individual transmits the disease, on average, to more than two persons it results in an epidemic? Can you comment on this?
Thank you for the clarification. I'm afraid I need more, however. After reading your article twice, I am still walking away unable to define 'infectivity.' Or confidently describe its exact distinction from 'transmissibility.'
My guess is that infectifity is a property of a pathogen with respect to species of cells, and transmissibility is a property of a pathogen with respect to species of entire organisms.
Can you help?
thanks in advance
One aspect that I have not seen addressed: Many are predicting that should H5N1 become easily transmissible, we could/should expect about 25-30% of the population to fall ill over the course of the pandemic. What's happening in the other folks? Are they not being exposed? Are they being exposed but not falling ill? And if that's the case, what is it about their infection that does not lead to disease? Is their body just developing anitbodies faster than the bodies of those who do fall ill? Or is it strictly a matter of viral load, as mentioned by "Name"? Or something else?
Jeez. I go away for a few hours of meetings (lucky me) and return to find all these questions. I guess I didn't do such a good job of explaining. So let me try to clarify the good questions (in reverse order because that way I don't have to scroll up first):
Dan: There are a lot of ways a viral particle could not cause disease or even infection. It might never find a competent cell to infect. The person might have adequate "pre-infection" defenses like copious mucus with dummy receptors in it, good clearance mechanisms, or who knows what. Some of those not sick really have inapparent infection. We don't know all the answers, but it is unusual for 100% of those exposed to become infected.
Suzanne: Infection really refers to cells. It means the virus has successfully found a competent cell to hijack and make copies of itself. If those copies don't make it to other cells, that's the end of it. To be transmissible, the virus also has to get out of you and into someone else. Some viruses make you sick in ways to facilitate this, for example, making you cough or sneeze or have diarrhea. But it is not the same as infection, which is the ability to replicate in an individual cell. The distinction you made in your comment does capture this idea.
Name: You are correct that there are different degrees of pathogenicity (the ability to make someone sick, not just infect them). Virulence refers to the severity of sickness, not just the fact of sickness. Thus a pathogenic virus can be of varying degrees of virulence, although we don't usually speak of mild diseas as "mild virulence." Virulence connotes serious disease, although you could also say a virus that usually causes mild disease isn't very virulent. So you are sort of correct in saying pathogenicity is "on-off" and virulence is a matter of degree. I say "sort of" because what counts as being "sick" can be a gray area.
The host-agent-envoironment idea is important. We often talk (as I just did) of a virulent virus, but in reality virulence isn't a property of the virus but in the combination of the virus, a particular host or host species and the environment both find themselves in. Certain viruses (or more commonly bacteria) are bad news in some environments and not others (e.g., temperature, humidity, host characteristics, particular tissues) and some hosts are only mildly affected and others seriously affected. AIDS patients, for example, are prone to virulent infections from organisms that are harmless to others. It isn't the organism that is virulent but the combination of the organism and the host.
everett: Unfortunately if I use an extended entry format only the above the fold stuff will be shown in your RSS reader. For shorter posts I'll put the whole thing above the fold and you'll see it, but if there is an extended entry (Read more . . . ) you'll have to click through. Not much I can do about it, I'm afraid. Hi, by the way.
Do you have any whiz-wheel economists at the school or know of any who have done "bird flu" expected battled damage assessments in papers? I have seen a lot of speculative stuff, and I have seen the stuff that DHS has, but its only for a two million mortality rate.
Also remember that projection model that they used a month or two ago showing how it would spread? I hear they have one now that shows a 2 million (1 or so%), 20 million (10%) and then the big banana of 114 million (40%).
If you know the site that has both or either pls advise
One more. carl's entry got caught in the spam filter. No idea why. He is asking what epidemiologists call an epidemic.
This is purely a judgment call. Technically it is just the occurrence in a region or locality of cases beyond what you normally expect. This means it is relative to a time, a place and a population (all of which, technically, should be precisely specified but often aren't). Two cases of a cold aren't an epidemic but two cases of rabies in the same place might be (one case is never an epidemic, however). When something is called an epidemic might differ between two health officials and it is a plastic word that is loaded with other meanings so is liable to be manipulated in either direction.
Epidemics refer to human populations, strictly speaking (it comes from Greek roots, meaning "upon the people"). The same thing in animals is an epizootic. The technical word for this in birds is an epornithic, but in all the things I've read bout H5N1 in birds I've never seen this word used. A pandemic crosses many international borders so that it involves large portions of the global population (although not necessarily all of it).
Bottom line: "epidemic" is a judgment call and has no "numbers" that define it.
Randy: I'm sure someone has done it and maybe a reader who follows this can tell us who and where.
Thanks again, Revere - that did it.
Re MRK's question, that sounds like something for Dr Bob Gleeson's "Bird Flu" Blog (http://drbobgleeson.typepad.com/bird_flu/)
He's medical director for a big insurance company - actuarial scenarios and risk management planning are right up his alley. His most recent post explores implications of one possible scenario while pointing out that no one knows which scenario will actually come to pass, if any.
Thank you very much, Revere, for this very helpful post. These distinctions are something I've been wondering about for a while, and it doesn't help that these terms are often used incorrectly or interchangeably. I learn something valuable every day that I read your blog.
I think its starting to weight in on people outside of the blog as to the enormity of what could happen. Thi s request was made as the wife of a VP at a brokerage firm joined my just the facts email list. She read what was being posted and then started printing it off for her husband to read when he got home. I got the call today for the "economics" question.
I only deal with actualities when they happen. On the other hand predictives I am really big into. My ex-commander once told me that if you prepare for the worst case you were just that ....prepared. If something happens you didnt think of, you were underprepared. If something happens that is bigger than the worst case projected, you are just screwed.
Revere, I say again I wish you would prepare. You are going to be needed to balance things if it comes.
Dr Gleeson's "moderate" scenario, by the way, is based on a pandemic far less severe than 1918, as are the scenarios being used by many planners. I don't think any authorities are planning for medium/worst case scenarios because even the best case scenarios are scary & challenging enough. Worst case is downright paralyzing.
Is it my computer settings or are the letters and lines squished together on this blog? It doesn't appear the same near the top with the wording under "profiles" or "recent posts"... those are easier to read.
I enjoy reading and learning from reading your posts. On this site, I will have to make sure I am very rested and very awake to unscramble the lines. I do not want to misinterpret what I am reading. :)
Floridagirl: What browser are you using? Older versions of Internet Explorere (IE) seem to be having a problem with this and other sites, too. If you are using IE I suggest migrating to Firefox ASAP, just on general principles. You'll get used to it fast and like it a lot more. Yo can import allyour IE bookmarks quickly and be ready to go in a flash.
If you are not using IE, let me know what you are using and I'll try to solve your problem with some help from the hivemind and Sb tech support.
I totally agree with the comment about the 'planning scenarios' that planners are using. In my interview last week with Dr. Eric Toner of the Center for Biosecurity, he was skeptical that the government is using the 1918 case death rate of about 2% when, in fact, this H5N1 is a different pathogen that could be worse and now has a 50%+ death rate. His words: "The government doesn't want to talk about these numbers." His biggest concern is the first "year of maximum exposure" when one-quarter or more of the U.S. population could contract the virus during the period when a vaccine is still in development and testing...and by 'vaccine' he meant a truly effective, virus-specific vaccine.
Reveres, If you don't mind my asking...Why do you choose not to prepare? Is it because you believe the likelihood is so remote that you do not? (I am basing this question on MRK alluding to this. Possibly it was covered earlier in a post I missed?)
Scorsbee: We do prepare but we spend all our energy where we think it is invested best, at the community level. We are public health people and those are the terms we think in. We just haven't done it on the individual level. We could have prescribed Tamiflu for ourselves but we had ethical qualms about it since we knew it would be rationed and we believed we should take whatever share the community eventually decided we should get. Everybody copes in different ways. Some people do individual prepping. We do community prepping.
Yeah, I did it... the site looks great. I have downloaded firefox and made you the home page. I cannot get rid of IE. I sometimes work form home and many of my programs rely on IE.... But, this is a solution, and I thank you for it. Know that I read everyday, but usually only post when I have questions or feel very strongly. (and if I am not in a class...)
While I am actually posting right now, Let me ask this question....
Do you know of any survey tools that are useful for assessing the public's knowledge on pandemic flu and assessing their preparedness for pandemic flu. The class I am in now, deals with community health.... Pandemic planning is an approved topic. I need some clinical hours and thought I would do a survey of the population.
Dont cut IE or your computer will not update to the latest Bill Gates disaster. As for your request as was with Dizzy of the UK I can pommel you with stuff from the WHO, DHS, FEMA, home grown stuff and really good stuff like "Where there is no doctor"
It will load up your inbox and I suggest you just create a file and dump it to a disk as it is BIG with a much bigger B than I can put onto here.
Your call, send me an email if you want it. Live libs and conservatives, thats the way I want my America after this shit comes to visit. Without a vaccine, the best thing for it is preparation and food.
M. Randolph Kruger,
Sent you an email...
floridagirl: depends a bit on what you want. As Randy suggests there are a lot of "checklists" out there for the public. But if what you want is a survey instrument, I don't know of one. You might try the Trust for America's health (google them) and ask them what they have. Maybe another reader has some info. Good luck.
Well, I think that Floridagirl is now drowning in all the stuff that I sent her. If anyone else wants to get their mailbox to go to maximum bandwidth just let me know. Its all about getting ready just in case. Hell it might be a smallpox pandemic instead of avian, but the preps are pretty much the same.
Everyone should be using their own email lists to inform, piss them off until they do something. We are the good email virus thats going to ensure a lot of people survive. There is a wealth of Revere, DHS, FEMA, homegrown stuff that will help if they do something with it now. I have preparedness lists for schools, school districts, businesses, local, state and federal. How you prepare will ensure yours and someone elses life will be saved.
I dont get into semantics when everyone states we are mathematically/statistically overdue for a pandemic. We have a hell of a lot of people on this planet and nature is going to take its course one way or another. We might come up with a vaccine, only to have it become worthless about 15 minutes after its made. Everyone is going to be in the blame game.
You will only be able to blame someone if you are alive. Feel free to email me if you want any of the lists such as preparedness, food lists, how to survive in a bio hazardous environment, what to expect from WHO, what to expect from CDC, what to expect from your state. See being part of the establishment gets you access to cool stuff. Its free for the asking and the bandwidth to send it.
Apologies in advance if what follows seems silly. My intent is to see if I understand the definitions of "pathogenicity" and "virulence", so I'm going to stetch things.
Virus A makes 95% of the people it infects "sick" - but not very. They get headaches, diarrhea, and miss a few days of work but never topping a week maximum. The only people who go to hospital are already in states so unstable that "you could kill them if you cut their hair".
Virus B only makes 5 to 10% of the people it infects "sick". But they get really sick. If you come down with clinical symptoms, you are going to feel like hammered shit at best. Expect to stay home for two weeks to a month. Many prayers will be offered to the Porcelain Throne, and Pedialyte will suddenly become more popular that Perrier. Hospital stays are common in people who report symptoms, and deaths are not unheard of.
If my understanding is correct, Virus A is clearly more pathogenic than Virus B. It's better at turning infection into observable "illness".
Can we also say that Virus B is more virulent than Virus A? Or is that definition skewed by the low probability of escalation from infection to clinical symptoms?
Edit: This blog now has a PREVIEW FEATURE! Hallelujah!
Charles: Both viruses are pathogenic (capable of causing disease), even though B does so less frequently. If it did so hardly ever, then we probably wouldn't call it pathogenic, although it would be potentially pathogenic. These terms are not that precise. Virus B is definitely more virulent. I think you have the idea exactly. The terms are general descriptive terms and not meant to be quantifiable, although it would certainly be possible to contruct quantifiable measures of each and sometimes people do so.
I will create my own this weekend. I have to get this done rather quickly. I meeting with Public Health tomorrow, we will see what turns up.
M. Randolph Kruger,
Thank you for sending me all the emails. I appreciate the fact that you took the time... It says alot about character.