Nematodes immune to anthelm. ? -Reply

Omar O. Barriga oobarrig at pop.service.ohio-state.edu
Mon Jan 27 23:44:29 EST 1997


        I would like to apologize to may friend Steve Kayes for what it looked like a criticism 
to his opinions. Actualy, I was concerned about how Steve's opinions might be read by 
farmers that occasionally read these newsletter. The major practical problem with drug 
resistance in veterinary medicine is the resistance of ticks to many acaricides (an old 
and very serious problem in Australia, South Africa, and other countries) and of helminths 
to some anthelmintics (an emerging problem in many countries, the USA included). I was 
afraid that non-specialists might read Steve's mail as saying that once a worm got 
resistant to thiabendazole, for example, it would be also resistant to ivermectins, for example 
(what is not what Steven was saying!). This DOES NOT happen in nature (at least to any important 
extent) and it is important to know that it does not happen because the way to eliminate 
a worm population that became resistant to one anthelmintic is to treat it very vigorously
with a very effective anthelmintic that acts throguh a different mechanism. 
        It is common, however, that resistance to one anthelmintic is often associated with resistance 
to another anthelmintics that acts through the same mechanism (all the benzimidazoles, for example).         
As far as we know, this is only an apparent case of multiple resistance because the gene product 
may block a single metabolic pathway that happens to be common to the activity of all the anthelmintics
involved.  

        The examples of the Schistosoma mansoni's glutathione S-transferase and the barbiturates 
as generating inducible inhibitors are very real. I believe that some 20 years ago somebody 
also described an inductible DDTase in domestic flies.  Yes, inducible enzymes do exist and 
some may even be involved in anti-drug resistance (such as the inducible DDTase). But I doubt
that this is a common occurrence among pesticides used to fight animal(including the human animal)
parasites. My feeling is that any pesticide that induces an inibiting substance in the host 
does not have much of a chance as a pesticide. Such a pesticide would act only the first time 
that is administered (the induced inhibitor would stop its action afterward) or the dose would 
have to be increased tremendously in the successive administrations (to overcome the inhibitor).
Would you put such an anti-parasitic drug on the market? Would you buy it?
     
        I know how much Steve Kayes enjoys a good intelectual discussion and I am sure that 
he is having great fun with our conversation. If there is any young fellow out there that enjoys 
science and is tinking of becoming a scientist, we scientists believe that it is our privilege 
to disagree. When every scientist holds the same opinion, the fun is over, we turn off the light, 
and go home.

        Cheers!
                                Omar O. Barriga




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