virulence

CGE at CU.NIH.GOV CGE at CU.NIH.GOV
Wed Dec 21 11:32:16 EST 1994


In Article <3d99bh$dn3 at martha.utk.edu> ctfaulkn at UTKVX.UTCC.UTK.EDU
writes:

->First, pathogenicity is NOT a relative term. An organism is either a
->pathogen or it is not.
->
-I have to disagree on this point because I accept the premise that
-pathogenicity varies for particular infections as a result of host
-and environmental factors, dose of the infective inocula, route of
-entrance of the infection, and source of the infection.  The example
-given in Mausner & Bahn (1985:268) is that staphylocci are not
-pathogens when located in the rectum, but when found in the
-peritoneal cavity or meninges serious disease results. I can think
-of other examples of clinical parasitism where this also occurs, for
-example Trichomonas gallinae generally causes no problems unless it
-gets in a different host (pigeon, for example) or is able to leave
-the digestive tract and invade new sites.  I don't think anyone will
-disagree that T.gondii has the potential to cause disease. However,
-many people are infected (25 to 50 % of the adult population, i this
-is an overestimate though) but few actually develope clinical
-toxoplasmosis, and even fewer die.  I would have to state that given
-these definition T.gondii (the average run of the mill isolate) is a
-parasite of low pathogenicity and low virulence in people.  The
-picture is different ,however, in kangaroos and lemurs where health
-animals secumb to clinical illness with almost any isolate.

I am not sure how you are differentiating pathogenicity and virulence
here. In the first sentence you are using pathogenicity as I would use
virulence. By the definitions I used what you describe above can be
summarized as follows:

Staphylococci are pathogens that in the rectum are avirulent but in
the peritoneum/meninges are virulent.

Trichomonas gallinae is a pathogen that is normally avirulent, but is
virulent in abnormal hosts.

Toxoplasma gondii is a pathogen of variable but usually low virulence
in humans (the recent work of Boothroyd and Sibley indicate that this
is a strain specific characteristic, in part) and is highly virulent
in certain other hosts.

->Only an organism that never causes disease should be called
->'non-pathogenic'.

-non-pathogenic under what circumstances?

Under all circumstances. Otherwise it is a pathogen of variable
virulence. For instance, I consider Entamoeba coli and E. hartmanni
to be non-pathogenic as they have never been clearly linked to
disease in any of the many primates in which they are found.

->Virulence IS a relative term - the relative capacity of a
->pathogen to cause disease under a defined set of circumstances. It
->HAS been clearly defined.
->
-I agree.  Or put another way, virulence is the proportion of
-'clinical cases' resulting in severe clinical mainfestations
-(including sequela). I was in error to imply that mortality had to
-be a necessary term in the definition. The CFR (case fatality rate)
-is simply one way to quantify virulence.

Virulence need not be directly linked to clinical manifestations.
Virulence is a spectrum from avirulent to death.

-I don't think Ewald is concerned about how an etiologic agent causes
-disease, only the observed effect either is does or does not.
-Concern then has to be directed at the population rather than the
-individual agent-host interaction.

Virulence can be a measure of an individual strain, not a population
or a species phenomenon. For instance, in Entamoeba histolytica one
way that virulence has been measured is to weigh the abscesses in
the livers of inoculated mice, and in Leishmania virulence has been
measured as diameter of foot pad lesions. In both species the
virulence level has been found to be characteristic of a strain or
even of a clone. However, this does not mean that populations or even
species do not have general characteristics - eg. North American
isolates of T. cruzi tend to be much less virulent than those from
South America.

As far as organisms with complex life cycles are concerned, I think
that it is simplest to keep the term 'pathogen' as a characteristic of
the species, even if it causes no pathology in certain intermediate
hosts. Thus one could say that Schistosoma mansoni is a pathogen that
is virulent in humans but avirulent in the snail (if that is in fact
true).

It seems that the major difference we have is over pathogenicity being
an either/or category. A similar discussion occurred a few years back
(in Science or Nature I believe) over use of the term homology. People
were using the term %homology with respect to DNA and protein
sequences. This is wrong, as genes and proteins are either homologous
or they are not. The terms %identity and % similarity are now used.

To me, pathogenicity is an absolute category while virulence is a
relative category. I believe this distinction simplifies the
terminology.

Graham
________________________________________________________
C. Graham Clark, Ph.D.
Laboratory of Parasitic Diseases,
National Institutes of Health,
Bethesda, MD 20892

Ph.: 301-496-4740
FAX: 301-402-4941
e-mail: cge at cu.nih.gov



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