My PhD thesis is around the spread of drug resistant malaria. The idea, from my supervisor, is that between sensitiveness (i.e. a parasite strain that is killed by a drug) and resistance (i.e. a parasite strain that that survives treatment) there are intermediate forms, tolerant forms, that are able to resist sub-terapheutic levels of treatment. The more I read, the more I like the idea. In fact, I think there is no thing like resistance or sensitiveness, there are only various degrees of tolerance. Let me explain:
Imagine a parasite (a single one, one in an infection of 10000000000 parasites), this guy is resistant to chloroquine and is exposed, by chance, to a MASSIVE amount of chloroquine. He will die (”he”, by the way, is a “it”, as we are talking about asexual forms. Although P. falciparum also has sexual forms). This interpretation is supported for instance, in the fact that chloroquine “resistant” infections can still be treated with chloroquine as long as the host has accumulated immunity (as in adults in malaria endemic areas). There is an “add-up” effect of the drug plus the immunity. Put it another way, a “resistant” strain is still partially affected by the drug.
The converse is also true, a sensitive (I should be saying highly intolerant) parasite might survive chloroquine treatment if either the drug level is sub-therapeutic or, shear luck of not crossing in the way of the drug.
There are good reasons for the existence of resistant and sensitive words though, I can think of at least two: First, from the outcome perspective - either the infection is cleared or not. Second from a cognitive and linguistic perspective: it is easy to talk and think about “black and white” sensitive and resistant than “gray toned” level of tolerance.
But I think that “resistant” and “sensitive” create a cognitive bias that undermines the ability to understand the underlying biological processes.
I prefer the notion of “tolerance” that, for me, is tightly associated to the notion of drop in parasite load per unit of time. A resistant infection, exposed to a drug, still has some drop in parasite load, but that is not enough to offset multiplication of surviving parasites (at least to bring the parasite count to 0). A tolerant infection, exposed to the same quantity of drug, has a big drop in parasite load, enough to offset the multiplication of surviving parasites that most probably will be eliminated soon.
The idea of tolerance and drop in parasite load also goes well with the importance of drug concentration.
4 Comments to "Drug resistance in malaria"
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Makes me wonder if malaria has the equivalent of bacterial persistence.
The idea of persistence brings another question to the modeling of how is the distribution of tolerance in the pathogen population and potential dynamics in this tolerance level.
‘resistace’ and sensitive’ in pharmacy/health is something not absolute , but relative and different slightly from linguistic definition. i do not see the problem n terms; rather i fear in implication: shall we give drug still for resistant strain at usual dose or a little higher or i other words does a sensitive organism respond adequately and always to the drug(i.e. does it not require care as to resistance for sensitive organism) ?
[…] But, much more importantly, it is still there because, it is both less expensive (it is easy to express half-life as a function of just the drug, than other parameters which might be still crucial in some situations) and still meaningful enough in many contexts (for instance, expressed as a function of drug it is still useful to compare the half-life of Artemether - short - against Sulfadoxine - long - for many kinds of reasonings). Even when the most economical concept entails some errors it might still be practical. The problem only arises when its simplicity has bad consequences (in this case, having wrong drug doses)… but, in certain contexts, it might be a problem, a serious problem (See my previous text about the notions of resistance, tolerance and sensitiveness for an example). […]