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Why is there almost no quinine resistance?
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6.10.08
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The product has been used for 360 years. This is in stark contrast to the resistance to other malaria drugs or antibiotic resistance in bacteria, where the “useful life” of a product is measured in years or a few decades. The concept of a standard dose was only developed in the twentieth century. Earlier the duration of treatment and the dosage were left to the discretion of the doctor. This, together with the fact that the concentrations of alkaloids varied greatly from plant to plant and that quinine was never pure, meant that malaria was treated with a therapy which must have produced the most varied blood levels. Yet no wide spread quinine resistance has been reported. The answer to the question why there is virtually no quinine resistance, could be very important. Is the target molecule of quinine so special that mutation is not possible? It would then be very helpful to know this target. It could also be that there is quinine resistance, but that it was not, and has not been recognised. However, this is doubtful. Is it that the present recommended dose is much higher than that which was formerly necessary? Is it the fact that “quinine” is actually a mixture of various active products, which prevents resistance developing? Resistance to combined therapy requires multiple, simultaneous mutations which is less readily achieved than that to single products. It is, however, possible that quinine has not previously been used at levels which create sufficient evolutionary pressure. The majority of malaria cases in Europe and America were P. vivax infections. Even in British India, P. vivax represented the lion’s share of infections. In P. falciparum endemic regions, only a few fortunate people were able to take quinine and then only when they had to (because of unpleasant side-effects). Few used quinine as a prophylactic agent (compared to the indigenous population). What is more, quinine has a short half-life, so that the parasite was only exposed to subtherapeutic concentrations for a short time. Probably its limited use is the reason for the absence of resistance, and with continuous use on a large scale, quinine resistance may yet become a reality in years to come.
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