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Video transcript

- [Voiceover] So, once Malaria has been confirmed by lab or by biochemical diagnosis treatment kind of has to start right away to give the person the best chance of survival, right, with as few complications as possible. So, let's say we're gonna use antimalarial drugs to treat the disease, right. So, to make sure we're using the right drugs we'll need to know a few things. So, we need to know what type of plasmodium is causing the infection, because some subtypes will just respond to drugs that others might not. We'll need to know how the patient's doing, right? Is this an uncomplicated Malaria, right, with, you know, flu-y symptoms, fevers, and chills that kind of stuff? Or is this severe Malaria with systemic life threatening symptoms? We'll need to know what we're dealing with. We'll also need to know if these parasites that are causing the infection, we need to know if they're resistant to any of our treatment. Maybe the infection was picked up in, you know, a part of the world known to have treatment resistant Malaria. So, there's a couple things we need to know right off the bat before we start treatment. So, let's say our patient over here he has uncomplicated Malaria, and let's remind ourselves that uncomplicated is still very serious, it can still be fatal. And, our patient over here, let's say he has severe Malaria. Notice that this guy, uncomplicated guy is just hanging out at home, right, he's still really exhausted and flu-y feeling, but he's at home. But, severe Malaria guy over here he's in a hospital bed and he's got an IV in and he's being monitored, he's being totally looked after by the hospital staff. And, that's because for uncomplicated guy over here he can take his antimalarial drugs in pill form. He can just take them at home. But, severe guy, remember he's having systemic symptoms, maybe his blood pressure is dangerously low or maybe he's severely anemic, or maybe he has brain symptoms, cerebral Malaria where he's having seizures or maybe his brain just isn't controlling his breathing properly, or maybe he's gone into a coma. So, he's in a hospital because in addition to getting antimalarials, which he'll get through this IV line here, he won't get them in pill form like this guy over here he'll need constant medical care to make sure that he survives, and with as few permanent complications as possible. So, let's talk about the types of medicines that can cure a Malaria infection. So, remember that there's essentially two stages of infection with Malaria. There's a liver phase where sporozorites infect your liver cells and multiply into thousands of merozoites. And then, there's a red blood cell phase where these little merozoites break out of your liver cells and infect your red blood cells. And, once they're inside your red blood cells they turn into what are called trophozoites. They hang out for a while and then they multiply into thousands more merozoites again. So, we have medications that can destroy these parasites at any of these stages, which is good. So, for uncomplicated Malaria the person usually gets treated with combination therapy which means that they take a few different drugs to treat their Malaria. So, they take usually two to three drugs because if you just use one drug to treat a Malaria infection well pretty quickly the parasites are gonna figure out how to become resistant, right, how to avoid being killed by that one drug. And, in fact, this is already a huge problem, there's already a lot of drug resistance that's cropped up in different parts of the world. So, that's why it's super important to use combination therapies to make sure that no potentially mutated parasites survive after treatment. Otherwise one day we just won't have any drugs left that work. So, the recommended combination for treating uncomplicated Malaria is called ACT: artemisinin combination therapy. And, artemisinin here is actually the name of a plant that we get this main drug in this combo from. The drug is called Artesunate and we get it from the artemisinin plant. So, Artesunate does a few things, it creates a really toxic environment in the parasites that can kill them. And, it interferes with some pretty important proteins on the plasmodium surface that allow them to get their nutrients. So, that makes it hard for them to stay alive too. And, the reason that ACT is built around this Artesunate drug here is because Artesunate is really, really effective against all the types of plasmodium. And, because there's not really much resistance to it right now, which is great. So, the standard combo is Artesunate, plus some other drug with a different mechanism of action. So, for example one that's commonly used is Mefloquine. Mefloquine here, which disrupts the acid base balance in the parasite and that's often lethal to the parasite. Or, sometimes you'll get a combo of two synergistic drugs Sulfadoxin and Pyrimethamine, which stops the Malaria from being able to replicate its DNA properly which means it can't really reporoduce very well in our bodies. These are just examples, there's other possibilites as well, though. So, what I just told you all this ACT stuff, that's the standard treatment of uncomplicated Malaria caused specifically by a plasmodium falciparum. ACT is really good at clearing a falciparum infection from the bloodstream. Plasmodium vivax, on the other hand, that has to be treated in a different way. So, for the blood stage you could still use ACT just like with falciparum, or often a drug called Chloroquin is used, but there's a fair amount of resistance to Choloroquin amongst Malaria parasites nowadays, mostly in south east Asia. But, how does Choloroquin work? Well, Malaria parasites feed on blood, they actually like the hemoglobin component of red blood cells, that's why they have such a blast in our bloodstream. But, when they're busy digesting the hemoglobin from a red blood cell they release the heme part of the hemoglobin molecule, right. So, they're just kind floating around because they don't wanna eat it, they just eat the globin part. And, free heme floating around here is actually toxic to both them, the parasites, and to the red blood cell that they're hanging around in. So, because they wanna stick around in the red cell for a while and, you know of course, because they wanna live the parasites convert this heme into crystals of hemozoin, which is not toxic to the cell or to them. So, Cholorquin and actually Mefloquin does this as well, these drugs prevent the parasites from converting the toxic heme into nontoxic hemozoin crystals, right? So, all of the resulting heme it builds up and it just makes the environment really toxic and then the parasites end up dying, which is great. So, that's the blood stage with plasmodium vivax but vivax is interesting though, it likes to hang out in the liver as well in a dormant phase, unlike falciparum. Falciparum sort of gets on with it and causes super severe infections pretty quickly, where as vivax, right, while it can still be really severe it takes it a bit slower so it likes to transform into what are called hypnozoites. And then, these hypnozoites take naps in the liver cells for extended periods of time. So, it's kinda like having a chronic Malaria infection with vivax. So, you have to kill the liver parasites, and you can do that with Primaquine which is actually effective against all types of Malaria, but we especially like it for how it deals with the vivax hypnozoites. Anyway, the Primaquine works by blocking oxidative metabalism in these hypnozoites in the liver. So, it stops them from being able to make enough energy to survive, so they die. Now, those are just the basic ideas of how you treat uncomplicated falciparum and vivax. You can see that there's quite a few different things to think about. But, if someone has severe malaria, right this guy over here, there's pretty much one thing that you always do. You stick in an IV, an intravenous line, right? And, you give the person Artesunate, remember that main drug in the ACT combo therapy. And, they can't take it in pill form, they need it to go straight into their bloodstream because there's not really any time to fiddle around with pills and all that. So, besides the IV Artesunate the person willl need supportive treatment, remember in severe Malaria the person might be having seizures, or they might be in a coma, or they might not be able to breathe on their own. So, they're gonna need respiratory support, and they'll probably also be really dehydrated so they'll need fluids and electrolytes as well. So, what sort of prognosis can you expect with Malaria treatment? Well, if you get proper treatment then usually you can expect a full recovery, especially with uncomplicated Malaria. And, this is all usually true with severe Malaria too, but it's important to keep in mind that severe Malaria can progress really quickly and it can also be a bit unpredictable. So, even with treatment and intensive care it still often still leads to death.