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.
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.
>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.
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.
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?
Hm..... There's only two studies in Cambodia, though. One of them apparently had a faillure rate of about 17%, which makes me think the other study had a failure rate of about 5%, to get a median of ~12% seen in the graph. Couldn't the high failure rate in Cambodia just be an artifact of an outlier study? Nearby Laos also has a low failure rate. Unfortunately, I don't see Thailand on the list, which would be another nearby country to compare with...
Since I have family that lives in Zambia and my daughter was there for three months this is scary. Mosquito born diseases kill more people than any other animal on earth. about 600,000 a year.
I'm not sure about other countries, but in Zambia at least the malaria rates are not spread uniformly around the country [1]. If your family is in Lusaka, for example, both they and your daughter should be pretty safe, especially if they take precautions like sleeping under a net.
You probably already know this, but if your daughter shows any symptoms of malaria, make sure you tell the examining physician that she's just returned from an area that is known to have malaria. It's often one of the first things doctors test for here in Zambia, but if you live in an area without endemic malaria, they might not test for it at all.
> You probably already know this, but if your daughter shows any symptoms of malaria, make sure you tell the examining physician that she's just returned from an area that is known to have malaria. It's often one of the first things doctors test for here in Zambia, but if you live in an area without endemic malaria, they might not test for it at all.
Also, for the blood test, make sure she actually has a fever when the blood is drawn.
Malaria (in the initial stages) may have a fever that comes and goes. The test has much higher false negative rates if the blood sample is drawn when the patient does not have a fever.
Doctors in areas where malaria is endemic generally know this, but doctors elsewhere may not. If she has any signs of a fever for the next ~2 months, it's best to get a blood sample drawn right away. Malaria is much more treatable when detected early.
Cambodia is highlighted here, but what isn't mentioned is that is specificially the border region of Thailand and Cambodia. I find that specifically worrying given the amount of travel that Thailand gets from around the world.
I remember reading a story a couple years ago of Thais crossing the border into Cambodia where artemisinin was cheap and unregulated, but I can't find it.
Resistance IS a big deal. I've lost my grandfather last monday due to nosocomial pneumonia (essentially, pneumonia resistant to all existing antibiotics).
Sulfadoxine-pyrimethamine is already unusable for malaria, except in combination with other drugs, because of high levels of resistance. This has been the case for years.
Johns Hopkins is developing a mosquito where the virus can't be transmitted, secondly the drug was developed in the 50s so the effective life of the drug at only ... only 70 years of use to just show slowness recently. With the research pace, the variation of reintroduced genetics will be less that 10. We are fine.
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.