HIV-1 Adaptation to host/various musings

Ian A. York york at mbcrr.dfci.harvard.edu
Tue Oct 24 20:31:00 EST 1995


In article <46g2qf$4gc at ipgate.le.ac.uk>, A.J.Cann <nna at le.ac.uk> wrote:
>
>Not to hand, but "at least 20,000" is hardly a reliable figure with which 
>to try to perform calculation accurate to 6 decimal places! C'mon, let's 
>not split hairs. 5 survivors is almost certainly a gross underestimate & 
>it's more complicated than that - the chances of survival when bitten on 
>the hands or feet are greater than if bitten on the face or neck.

Alan, I'm not just making this up, you know.  My "20,000" was a 
deliberately conservative figure.  From Ref [1] - a 1995 paper:  "In 
India alone, 30,000 to 50,000 people may die of rabies per year."  

My "five survivors" is also pretty accurate.  A letter [2] in New Engl. J. 
Med. in 1994 cited three case reports of humans surviving rabies in the 
1970's (1972, 1976, 1977) as buoying their enthusiasm for treating rabies, 
but concluded "Our initial enthusiasm and optimism gave way to a feeling 
of despondency and helplessness when we were faced with the relentless 
progression of this disease.  It does not seem practical to proceed 
aggressively.  Clearly, with respect to rabies the adage 'prevention is 
better than cure' should be modified to 'prevention is all, there is no 
cure."  

If we assume that I've missed some reports of survivors and call it 
20 surviving since 1970, and conservatively assume 50,000 cases per year 
in the world, the odds of death are somewhere around 99.999% - admittedly 
lower than my original 99.999999 but then, I haven't included the 100% 
mortality in the years of history before then.

>Well, in the sense that they survive long enough (years in some cases) to 
>transmit the virus to other hosts of the same species, yes, e.g. foxes, the 
>natural hosts for sylvan rabies.

Sorry, I'm going to have to ask you for some evidence for this "years of
survival".  Certainly there are well-documented cases of individuals
(humans) showing incubation periods of years, but I'm not aware of any
*species* that shows anything like that.  To the best of my knowledge
(reinforced by a check of Medline and a quick rummage through the library)
virtually all mammals are susceptible to rabies and none survives for 
very long after they become infectious.  

We may have a difference in definition, though:  It's certainly true that
some species (e.g. opossums, I believe) are more resistant to becoming
infected; but that's a different thing from becoming infected and then
surviving, as you state.  This also applies to your comment above that the
survival is different if you're bitten on an extremity vs. the face:  In
the former case the incubation period is certainly longer on average, and
the chances of becoming infected may be lower (I haven't seen any figures
for that) but the survival doesn't change from 0.  (To argue that being
bitten and not developing the disease equates to surviving the disease, is
like saying "I recovered from a cold" because you were in the same room as
a person with a cold but didn't catch it.  I realize you haven't made this
argument, I'm just clarifying myself.)

I also should note that naming foxes as "the" natural hosts of sylvan
rabies is not correct; while foxes are certainly one reservoir, skunks,
bats, and racoons in North America, and many other species in different
areas (eg mongooses etc) are 'natural hosts' in that they are major pools
of the disease, and as I say most if not all mammals are susceptible and
potential sources of infection. 

Moving back to the original intent of this discussion:  The original 
question was whether pathogens tended to become less virulent over time 
in their natural host.  I said this is not necessarily true, and cited 
rabies as an example of a virus that remains horribly virulent in all 
species it infects, despite a long association with its various hosts.  I 
still think that's true, and still think that the idea that pathogens 
necessarily, or even generally, become less virulent is oversimplified.

Ian

References -

[1]  Warrell DA, Warrell MJ.
Human rabies:  A continuing challenge in the tropical world.
Journal Suisse de Medecine 125:879-85, 1995

[2]  Udwadia ZF.
Rabies.
New Engl. J. Med. 330:1088, 1994

"In their excellent review of rabies Fishbein and Robinson make little 
mention of the care of patients with established disease.  In many 
developing countries, the patient load is high (5000 - 10,000 patients 
with rabies are seen annually in India), and the costs of treating these 
patients may be enormous.  Should precious time, money, and human 
resources be spent supporting these patients?  Or, since the eventual 
outcome is so dismal, should a passive approach of sedation be followed, 
leaving these unfortunate patients to die in relative comfort with 
minimal intervention?
	Buoyed by reports of the survival of patients with rabies in the 
1970's, we attempted over a period of 14 months (February 1985 to April 
1986) to treat some of the patients admitted to the rabies ward of the 
J.J. Hospital in Bombay, India, aggressively.  All such patients received 
early elective tracheostomies, ventilatory support, cardiac monitoring, 
and intensive care for the myriad complications of rabies.  Our results 
were not encouraging.  The 8 aggressively treated patients survived for 
an average of 14.5 days, as compared with a survival of 2.5 days amongst 
the 12 patients who were treated conservatively.  The longest surviving 
patient lived for 25 days after the onset of illness.  
	Our initial enthusiasm and optimism gave way to a feeling of
despondency and helplessness when we were faced with the relentless
progression of this disease.  It does not seem practical to proceed
aggressively.  Clearly, with respect to rabies the adage 'prevention is
better than cure' should be modified to 'prevention is all, there is no
cure."

-- 
Ian York   (york at mbcrr.harvard.edu)
Dana-Farber Cancer Institute, 44 Binney St., Boston MA 02115
Phone (617)-632-3921     Fax  (617)-632-2627




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