7 ms·

Not necessarily. Current prevalence of resistance to artemisinin is mostly due to what happened shortly after the drugs discovery. That is, wide-spread single-

by searine 11y ago

Not necessarily. Current prevalence of resistance to artemisinin is mostly due to what happened shortly after the drugs discovery. That is, wide-spread single-mode-of-action use. This was due to uncontrolled over-the-counter use in South East Asia, which in recent years has been curtailed. While this still happens, the WHO has gotten much much better at making sure combined therapies are used, which is the essential bit to controlling resistance. The only tool we have to combating biological resistance (in any organism) are combined therapies. Doing so hijacks the mathematics of natural selection to make it almost impossible to evolve resistance (given high enough stacks of modes-of-action and complete treatment courses). As the graph in the article shows, artemisinin resistance is still mostly contained to where it originally evolved (cambodia). Given careful management, we can expect slow spread, if any at all. Fighting malaria isn't a one-punch win. It is a marathon, but one that we are very slowly winning. The disease is trending downwards and we are finally making in-roads into the most endemic regions. This slow reduction in the disease burden worldwide makes resistance harder and harder for the parasite to evolve. Drug resistance is deadly serious, but I'm not as pessimistic as this article. Given proper tracking of resistance, and management, we'll easily have several more decades of artemisinin use.

dogma1138 11y ago
Malaria parasites are capable of both asexual and sexual reproduction. While the only reproduce asexually within the secondary host the reproduce sexually within the primary host (mosquitoes) this means that if you have parasites that individually develop a resistance to different drugs within the secondary host (humans) could result in combined resistance once they sexually mate back within the primary host. Malaria is also one of the most polymorphic single cell organisms in existence which is one of the main reasons why vaccination attempts were pretty futile so far which might give it a much better chance to develop resistance.
BurningFrog 11y ago
It's very hard for me to believe combined therapies can beat evolution. I can believe that it takes evolution longer to adapt to it. Of course I don't even know what "combined therapies" is, so I'm probably wrong. What am I missing?
- monochromatic 11y ago
  If a malaria parasite has a one-in-a-million chance of being resistant to a given drug, then it has only a one-in-a-trillion chance of being resistant to two drugs.
  - mapt 11y ago
    *Which act via different mechanisms of action, are equally effective, and whose assaults on the parasite have an equal chance of working
    - monochromatic 11y ago
      Right. I'm definitely oversimplifying.
      - chc 11y ago
        I'd say you were just simplifying, no over- about it. That seemed like a good level of simplicity for the explanation.
    - deleted 11y ago
      [deleted]
    - Abraln 11y ago
      So would a decent formula for drugs A and B be: rAdiff x rBdiff x rshared = r% where the rA/Bdiff is the chance of resisting the unique parts of A and B and rshared is the chance of resisting what is shared between them?
  - ethbro 11y ago
    Or in essence, turning the random nature of mutation into a liability instead of a strength. The odds of evolving multiple resistance in parallel are minuscule compared to developing it in series.
- searine 11y ago
  >It's very hard for me to believe combined therapies can beat evolution. Obviously the faster an organism mutates/replicates the harder it is to slow/stop evolution. HIV for example is "worst case scenario" but with combination therapies we've managed to make HIV a treatable disease. At the end of the day it all boils down to one hard fact. An organism can't evolve if it is extinct. Selection works by causing deaths in a population (ex selecting those which live on). If you raise the "cost of selection" so high that an organism can't pay the cost in deaths, the population goes extinct. As a rule of thumb, to fix an adaptive change, it takes 20 times the population in deaths. So if the current population is 1000, it'll take 20,000 deaths (and by deaths I mean removing an unfit allele from the population) over many generations to fix that adaptive allele. >Of course I don't even know what "combined therapies" is, so I'm probably wrong. What am I missing? Therapies or methods that employ more than one independent mode-of-action. Ex: Two drugs given at the same time. This forces the organism to adapt to two things at once, doubling the cost of selection. As you increase modes of action, the cost rises to the point that it is impossible to adapt before the population goes extinct.
chaostheory 11y ago
> This was due to uncontrolled over-the-counter use in South East Asia, which in recent years has been curtailed. I hope that you're right, because from what I have seen recently there's still a lot of prescription drugs that you can get otc

by searine 11y ago

dogma1138 11y ago

Malaria parasites are capable of both asexual and sexual reproduction. While the only reproduce asexually within the secondary host the reproduce sexually within the primary host (mosquitoes) this means that if you have parasites that individually develop a resistance to different drugs within the secondary host (humans) could result in combined resistance once they sexually mate back within the primary host. Malaria is also one of the most polymorphic single cell organisms in existence which is one of the main reasons why vaccination attempts were pretty futile so far which might give it a much better chance to develop resistance.

BurningFrog 11y ago

It's very hard for me to believe combined therapies can beat evolution. I can believe that it takes evolution longer to adapt to it. Of course I don't even know what "combined therapies" is, so I'm probably wrong. What am I missing?

monochromatic 11y ago
If a malaria parasite has a one-in-a-million chance of being resistant to a given drug, then it has only a one-in-a-trillion chance of being resistant to two drugs.
- mapt 11y ago
  *Which act via different mechanisms of action, are equally effective, and whose assaults on the parasite have an equal chance of working
  - monochromatic 11y ago
    Right. I'm definitely oversimplifying.
    - chc 11y ago
      I'd say you were just simplifying, no over- about it. That seemed like a good level of simplicity for the explanation.
  - deleted 11y ago
    [deleted]
  - Abraln 11y ago
    So would a decent formula for drugs A and B be: rAdiff x rBdiff x rshared = r% where the rA/Bdiff is the chance of resisting the unique parts of A and B and rshared is the chance of resisting what is shared between them?
- ethbro 11y ago
  Or in essence, turning the random nature of mutation into a liability instead of a strength. The odds of evolving multiple resistance in parallel are minuscule compared to developing it in series.
searine 11y ago
>It's very hard for me to believe combined therapies can beat evolution. Obviously the faster an organism mutates/replicates the harder it is to slow/stop evolution. HIV for example is "worst case scenario" but with combination therapies we've managed to make HIV a treatable disease. At the end of the day it all boils down to one hard fact. An organism can't evolve if it is extinct. Selection works by causing deaths in a population (ex selecting those which live on). If you raise the "cost of selection" so high that an organism can't pay the cost in deaths, the population goes extinct. As a rule of thumb, to fix an adaptive change, it takes 20 times the population in deaths. So if the current population is 1000, it'll take 20,000 deaths (and by deaths I mean removing an unfit allele from the population) over many generations to fix that adaptive allele. >Of course I don't even know what "combined therapies" is, so I'm probably wrong. What am I missing? Therapies or methods that employ more than one independent mode-of-action. Ex: Two drugs given at the same time. This forces the organism to adapt to two things at once, doubling the cost of selection. As you increase modes of action, the cost rises to the point that it is impossible to adapt before the population goes extinct.

chaostheory 11y ago

> This was due to uncontrolled over-the-counter use in South East Asia, which in recent years has been curtailed. I hope that you're right, because from what I have seen recently there's still a lot of prescription drugs that you can get otc