WEBVTT 00:00:00.733 --> 00:00:04.266 this is David Anderson doing my last presentation for this transfusion 00:00:04.266 --> 00:00:05.600 medicine rotation. 00:00:05.600 --> 00:00:09.133 And today I will be presenting on post our testing rate 00:00:09.533 --> 00:00:14.466 delayed homologous. See? 00:00:17.600 --> 00:00:18.133 All right. 00:00:18.133 --> 00:00:19.400 So the objectives for today 00:00:19.400 --> 00:00:23.133 are to review the pathophysiology of Plasmodium falciparum malaria. 00:00:23.733 --> 00:00:27.466 You are testing its mechanism of action and then review 00:00:27.933 --> 00:00:30.933 our tests in eight delayed hemolysis. 00:00:33.266 --> 00:00:36.000 So, the patient that kind of, 00:00:36.000 --> 00:00:40.466 stemmed the interest in this topic was a 61 year old male with hypertension. 00:00:41.133 --> 00:00:43.800 He was transferred here from an outside hospital with metabolic 00:00:43.800 --> 00:00:47.600 acidosis, acute kidney injury, and hypoglycemia 00:00:47.866 --> 00:00:51.600 in the setting of severe malaria and an incidental Covid infection. 00:00:51.600 --> 00:00:55.133 Five days after returning from a hunting expedition in Mozambique. 00:00:56.866 --> 00:01:00.266 He had kind of inquired about getting malaria prophylaxis, 00:01:00.266 --> 00:01:01.733 but it was too close to his trip 00:01:01.733 --> 00:01:04.666 and wasn't able to obtain it, so he didn't take any. 00:01:04.666 --> 00:01:05.066 And then, 00:01:06.066 --> 00:01:07.733 his, smear, 00:01:07.733 --> 00:01:11.400 once they were working him up for malaria, showed Plasmodium falciparum, 00:01:12.000 --> 00:01:15.733 in the ring and was right farm and then his parasite tenia level 00:01:15.733 --> 00:01:20.400 came back at 24.4% and peaked at 32%. 00:01:21.066 --> 00:01:24.400 And kind of what anything greater than 5% is where we start, 00:01:25.133 --> 00:01:28.733 considering it to be like, serious infection. 00:01:29.533 --> 00:01:34.266 And so he was started on our testing it every 12 hours for three doses. 00:01:34.266 --> 00:01:39.133 And then, after that, he was on a, once a day daily from basically, 00:01:39.800 --> 00:01:42.400 the 15th of August through the 18th 00:01:42.400 --> 00:01:45.533 until his parasitic male level dropped below 1%. 00:01:45.600 --> 00:01:50.333 And then they followed that up by a combination drug called Corten, 00:01:51.800 --> 00:01:52.533 twice a day. 00:01:52.533 --> 00:01:54.533 And then, that lasted three days. 00:01:54.533 --> 00:01:59.933 So about three days after the completion of the second medication, 00:02:00.400 --> 00:02:03.533 he began to feel more fatigued with intermittent mild fevers and, 00:02:03.866 --> 00:02:06.000 noticed that his urine was becoming pretty dark. 00:02:06.000 --> 00:02:10.600 So he came to the Ed on the 29th and was found to be lacking, 00:02:10.600 --> 00:02:13.133 but hemodynamic, stable and a febrile. 00:02:13.133 --> 00:02:17.600 But he was CVC was noticeable for hemoglobin a 5.1, 00:02:18.200 --> 00:02:22.600 while his platelets remained, pretty normal at, 363 00:02:24.466 --> 00:02:25.466 and then so 00:02:25.466 --> 00:02:30.133 I kind of really briefly mentioned malaria during my sickle cell disease talk. 00:02:30.533 --> 00:02:34.066 In the context that phylogenetic analysis, using data from various 00:02:34.066 --> 00:02:37.600 genome databases, determined that the hemoglobin S, 00:02:39.733 --> 00:02:40.600 being type of was 00:02:40.600 --> 00:02:44.666 about 7000 years ago in either West or Central Africa. 00:02:45.200 --> 00:02:48.333 And, then this was like the equatorial rainforest. 00:02:48.333 --> 00:02:50.333 So it was very rainy and wet 00:02:50.333 --> 00:02:53.733 and allowed mosquitoes to thrive in malaria to be endemic. 00:02:54.466 --> 00:02:57.800 And then, the regions of equatorial Africa where malaria is 00:02:57.800 --> 00:02:59.266 a major cause of death coincide 00:02:59.266 --> 00:03:03.200 pretty closely with areas where sickle cell, the sickle cell gene, is prevalent. 00:03:03.200 --> 00:03:07.666 And so, since then, the observations been made that individuals 00:03:07.666 --> 00:03:12.133 heterozygous for HBS are less likely to die of a malarial infection. 00:03:12.733 --> 00:03:14.600 And so, 00:03:14.600 --> 00:03:16.933 to kind of put it into context, the region of Africa 00:03:16.933 --> 00:03:20.133 where malaria is endemic contributes to childhood mortality rates as high 00:03:20.133 --> 00:03:23.133 as 50%, particularly in children under five. 00:03:23.600 --> 00:03:27.666 And then, of course, it also, affects pregnant women, patients with HIV. 00:03:27.666 --> 00:03:32.666 And then, travelers like this individual with no kind of, exposure to malaria. 00:03:33.000 --> 00:03:33.733 Previously. 00:03:34.733 --> 00:03:38.333 So in reality, the malaria belt is along the equator, 00:03:38.333 --> 00:03:42.133 and it also extends into Latin America, South Asia and Southeast 00:03:42.133 --> 00:03:45.133 Asia. 00:03:45.333 --> 00:03:46.533 And so, 00:03:46.533 --> 00:03:49.466 malaria is an infection caused by the Plasmodium species, 00:03:49.466 --> 00:03:52.466 which are single celled parasites that get spread by mosquitoes. 00:03:52.933 --> 00:03:56.400 There are actually hundreds of different types of the species. 00:03:56.400 --> 00:04:01.466 But, this list of five basically are the ones that cause, malarial disease. 00:04:01.733 --> 00:04:04.133 And then the process for each of these five, 00:04:04.133 --> 00:04:07.266 in terms of how they infect and survived is slightly different. 00:04:07.266 --> 00:04:10.333 But I'm going to focus just on that falciparum today, 00:04:10.400 --> 00:04:13.400 since this is what our, patient was, or 00:04:13.466 --> 00:04:16.466 this is the species that our patient had. 00:04:17.733 --> 00:04:19.866 So here's like a nice, 00:04:19.866 --> 00:04:23.666 kind of info or graph of the, the life cycle, 00:04:24.800 --> 00:04:28.133 and kind of just the whole process, taken from the CDC website. 00:04:29.000 --> 00:04:31.866 So basically, we start up here, 00:04:31.866 --> 00:04:35.733 the malaria starts with the Plasmodium infected Anopheles mosquito. 00:04:35.933 --> 00:04:37.400 And, it's basically, 00:04:38.866 --> 00:04:41.666 it's going to start when it hunts for a blood meal. 00:04:41.666 --> 00:04:46.733 So, at this point, the plasmodium is in a stage of development called the parasite. 00:04:47.200 --> 00:04:50.000 And it's, this pa as I, 00:04:50.000 --> 00:04:54.600 this Barroso, rest in the mosquito salivary gland and basically, 00:04:55.200 --> 00:04:58.733 once the mosquito inserts its proboscis into the, 00:04:59.600 --> 00:05:02.600 like, future patients blood vessels. 00:05:02.933 --> 00:05:06.466 Despereaux, though it's within minutes, will find its way into the 00:05:06.533 --> 00:05:09.533 Or through the, bloodstream, into the patient's liver. 00:05:10.666 --> 00:05:14.600 And, basically here it, enters the exo 00:05:14.600 --> 00:05:19.266 or rather acidic phase called that because it's outside of the retro site. 00:05:20.066 --> 00:05:23.066 And, this phase is generally asymptomatic. 00:05:23.266 --> 00:05:25.733 It can last from, like 1 to 2 weeks. 00:05:25.733 --> 00:05:29.866 And then, here the P falciparum is going to multiply asexually, 00:05:30.400 --> 00:05:31.866 and it'll kind of mature a bit. 00:05:31.866 --> 00:05:32.933 It'll become Morozov. 00:05:32.933 --> 00:05:33.400 Right. 00:05:33.400 --> 00:05:36.200 And, this is all happening while the host, 00:05:37.866 --> 00:05:38.733 perineum, all cells 00:05:38.733 --> 00:05:44.000 die and then some, from here, the marzo are going 00:05:44.000 --> 00:05:47.000 to get released into the, or from the liver. 00:05:47.533 --> 00:05:49.000 Kind of down into the blood. 00:05:49.000 --> 00:05:52.266 And it's going to bind onto the surface receptors of RBCs. 00:05:53.600 --> 00:05:56.600 Kind of on that list of the five different species of, 00:05:57.400 --> 00:06:01.333 Plasmodium, they kind of have different preferences for, 00:06:02.733 --> 00:06:05.333 different, like aged RBCs, but 00:06:05.333 --> 00:06:08.333 the P falciparum can have been star RBCs of all ages. 00:06:09.000 --> 00:06:12.333 And then once it, invades the erythrocyte, 00:06:13.466 --> 00:06:17.333 that's the start of the arithmetic phase, or orthostatic cycle. 00:06:17.933 --> 00:06:21.933 And then so here the Arizona undergoes asexual reproduction for 2 to 3 days. 00:06:22.533 --> 00:06:26.400 And in this first stage, the p file system is in ring form. 00:06:26.400 --> 00:06:30.933 So, and the trapezoid and that's what we saw on the patient's, 00:06:32.000 --> 00:06:33.266 smear. 00:06:33.266 --> 00:06:35.400 And then in the second stage, it's the trapezoid. 00:06:35.400 --> 00:06:40.866 It's going to grow and it's known as a, late or mature, trapezoid at that point. 00:06:41.266 --> 00:06:44.266 And then in the third and final stage, 00:06:44.866 --> 00:06:46.600 the trapezoid is known. 00:06:46.600 --> 00:06:50.733 This gets on and continues to grow and gets nutrients by digesting hemoglobin 00:06:51.266 --> 00:06:53.333 and it leaves behind. 00:06:53.333 --> 00:06:56.333 I don't know if you can see it in this little infographic, but this little, 00:06:57.266 --> 00:07:01.066 kind of like brown, deposit, which kind of like, 00:07:01.066 --> 00:07:04.800 will be described as like a little fecal smear intracellular area. 00:07:04.800 --> 00:07:08.266 So I know it's rude and then, and now undergoes 00:07:08.266 --> 00:07:11.800 mitosis and replicates and differentiates into different parasites, and then, 00:07:12.933 --> 00:07:15.400 some of them kind of just continue with this cycle 00:07:15.400 --> 00:07:19.533 and then, other ones continue along and undergo 00:07:21.733 --> 00:07:24.733 kind of this differentiation and to give me the sites here. 00:07:24.800 --> 00:07:28.333 So they kind of develop these, male and female counterparts 00:07:28.333 --> 00:07:32.400 and they remain into the RBCs until they again get sucked up 00:07:32.400 --> 00:07:35.533 by, the mosquito that is, feeding on, 00:07:36.600 --> 00:07:39.133 another blood model, essentially. 00:07:39.133 --> 00:07:43.133 So, in the mosquito's got the, the, 00:07:44.133 --> 00:07:47.133 the media sites will kind of remain here for a little bit. 00:07:47.800 --> 00:07:49.800 And then they, 00:07:49.800 --> 00:07:52.800 they undergo a process called progeny, 00:07:53.000 --> 00:07:55.733 which is a form of sexual reproduction. 00:07:55.733 --> 00:07:59.400 And so the, the zygotes that mature into these, Oakengates 00:07:59.600 --> 00:08:01.666 and then these are assessed 00:08:01.666 --> 00:08:04.933 and then, these, cells are going to rupture and, 00:08:05.533 --> 00:08:09.000 basically collect in the mosquito's gut and then, 00:08:09.800 --> 00:08:13.066 once they rupture, there's a release at the spa associates again, 00:08:13.333 --> 00:08:16.333 and then they make their way to the mosquito salivary glands 00:08:16.600 --> 00:08:20.133 and then, that the whole process basically starts over. 00:08:22.666 --> 00:08:26.400 And. You hear 00:08:26.733 --> 00:08:31.600 so, of all the Plasmodium species, falciparum causes the worst infection. 00:08:32.466 --> 00:08:36.466 Most Plasmodium infected RBCs are screened and destroyed by the spleen, but 00:08:37.200 --> 00:08:40.466 falciparum, in particular generates a sticky protein that 00:08:40.466 --> 00:08:44.266 because the surface of the infected RBC with these little knobs, 00:08:44.266 --> 00:08:48.200 which in turn causes clumping of the RBCs inside of adherence. 00:08:48.533 --> 00:08:50.866 And so they, essentially bind to the vessel 00:08:50.866 --> 00:08:53.866 and never make it to the spleen due to that, like, 00:08:54.133 --> 00:08:56.533 evasive adaptation that they have. 00:08:56.533 --> 00:08:57.866 So it, 00:08:57.866 --> 00:09:01.200 I kind of mentioned this in the articles, all talk, but it creates these knobs 00:09:01.200 --> 00:09:06.000 by increasing the acidity of the inner contents of their astrocyte by 0.4 units. 00:09:06.266 --> 00:09:10.466 And this allows the erythrocytes that here the proteins lining the capillary walls. 00:09:10.933 --> 00:09:12.933 So as you can imagine, 00:09:12.933 --> 00:09:16.800 with this process of site adherence, they can block the vessels. 00:09:16.800 --> 00:09:19.466 They can also and in the process, 00:09:20.400 --> 00:09:21.866 block blood to vital organs. 00:09:21.866 --> 00:09:25.733 So, you have a picture of, like, hemolytic anemia going on 00:09:26.066 --> 00:09:28.200 that can be a picture of ischemic damage going on. 00:09:28.200 --> 00:09:31.533 And it's pretty easy to imagine how this can lead to organ failure. 00:09:32.933 --> 00:09:35.866 And then, as I mentioned in the sickle cell talk, 00:09:35.866 --> 00:09:38.800 this confers an adaptive advantage in a couple of ways. 00:09:38.800 --> 00:09:42.333 And then, first, in their early stages of the malarial infection, 00:09:42.866 --> 00:09:45.333 the increased acidity mechanism 00:09:45.333 --> 00:09:48.333 that it uses actually causes greater cycling. 00:09:48.333 --> 00:09:53.400 So it goes from, 40% cycling versus the normal 2% that you would expect. 00:09:53.666 --> 00:09:55.866 And so the rest of sites are preferentially removed 00:09:55.866 --> 00:09:57.600 from the circulation for being defective. 00:09:57.600 --> 00:09:59.266 In that sense. 00:09:59.266 --> 00:10:02.333 And then number two, the ones that managed to survive, 00:10:03.266 --> 00:10:07.133 the cycling process by that or not, the signal process, 00:10:07.133 --> 00:10:09.666 but the ones that managed to survive going to the spleen, 00:10:10.733 --> 00:10:11.466 by attaching to 00:10:11.466 --> 00:10:14.466 the capillary proteins tend to cycle anyways 00:10:14.466 --> 00:10:17.466 because they're in a relatively lower oxygen environment. 00:10:17.466 --> 00:10:22.133 And then so, they'll basically become mechanically and metabolically disrupted. 00:10:22.133 --> 00:10:23.866 And then, 00:10:23.866 --> 00:10:26.866 and that actually destroys the parasite itself. 00:10:27.200 --> 00:10:32.333 So treatment is generally divided by the stage of infection. 00:10:33.000 --> 00:10:36.733 Chemo prophylaxis or suppressive treatment is usually given to travelers 00:10:36.733 --> 00:10:39.733 that are heading to a country with endemic malaria. 00:10:40.200 --> 00:10:43.600 Like this individual is aiming, for. 00:10:44.200 --> 00:10:46.800 And then so the goal of this is to kill these parasites before 00:10:46.800 --> 00:10:49.800 they infect the parasites in the first place. 00:10:50.333 --> 00:10:53.800 And then, therapeutic treatment is aimed at eliminating mares. 00:10:53.800 --> 00:10:56.800 Oh, it's in the objective setting phase. 00:10:56.866 --> 00:10:59.066 There's also, give me the cycle. 00:10:59.066 --> 00:11:00.066 Kind of classic drugs 00:11:00.066 --> 00:11:04.000 that cure, the give me the sights kind of later on in, the life cycle. 00:11:05.000 --> 00:11:09.200 So it's important to note that, a single infection 00:11:09.200 --> 00:11:12.200 doesn't confer immunity, but recurrent malaria, 00:11:13.333 --> 00:11:18.000 or. Sorry, but, previous exposure or infection can, help 00:11:18.000 --> 00:11:22.000 one adapt to, like, the severity of future infections, essentially. 00:11:22.533 --> 00:11:25.533 But recurrent malaria can occur in three ways. 00:11:25.800 --> 00:11:28.266 The first is recrudescence. 00:11:28.266 --> 00:11:30.933 So essentially this is from ineffective treatment. 00:11:30.933 --> 00:11:33.933 So, the infection was never cleared in the first place. 00:11:34.000 --> 00:11:35.933 And this is, of course, going to be like 00:11:35.933 --> 00:11:38.933 common where you have high antimalarial resistance. 00:11:39.800 --> 00:11:42.800 Number two is, you have early relapse. 00:11:43.066 --> 00:11:45.400 So essentially the blood is cleared of the mares. 00:11:45.400 --> 00:11:48.400 All right. With the first and, 00:11:48.533 --> 00:11:51.400 kind of bout or wave of infection, but happens. 00:11:51.400 --> 00:11:53.266 So it's persisted in the liver. 00:11:53.266 --> 00:11:55.866 And so I didn't talk about Hypnos. All right. 00:11:55.866 --> 00:12:02.066 With falciparum, it's more specific to the, p vivax in the Po Valley, 00:12:02.066 --> 00:12:05.266 but they can essentially go into this, like, quiescent. 00:12:05.466 --> 00:12:09.133 It kind of like under the radar, phase where they're just, 00:12:09.600 --> 00:12:11.133 can wait there for months, 00:12:12.400 --> 00:12:14.333 before they show any symptoms. 00:12:14.333 --> 00:12:17.800 And then number three, there's reinfection where an individual 00:12:17.800 --> 00:12:20.800 was effectively treated, but they just, had the 00:12:20.866 --> 00:12:24.133 the bad luck of getting a new infection caused by a new bout of malaria. 00:12:24.666 --> 00:12:27.666 And, the reinfection is common in, 00:12:27.733 --> 00:12:30.400 endemic areas. 00:12:30.400 --> 00:12:34.800 So, as I mentioned, this patient was treated with our test, 00:12:34.800 --> 00:12:37.933 and it this is under the class of drugs called, 00:12:39.000 --> 00:12:41.933 artemisinin is and, 00:12:41.933 --> 00:12:45.400 artemisinin is, are essentially, inactive when they're given. 00:12:45.400 --> 00:12:48.466 And they're activated by various or two plus, 00:12:49.400 --> 00:12:51.466 iron or, freaking. 00:12:51.466 --> 00:12:54.600 So in this diagram, the art is the or testing it. 00:12:54.600 --> 00:12:57.600 And then, I guess it's a British diagram, 00:12:57.733 --> 00:13:00.666 with the he was built this way. 00:13:00.666 --> 00:13:03.266 And then it kind of shows like the, 00:13:03.266 --> 00:13:05.866 different mechanisms that it might act on. 00:13:05.866 --> 00:13:06.666 It seems like it's not, 00:13:08.400 --> 00:13:09.666 known for sure exactly 00:13:09.666 --> 00:13:13.533 how it works, but these are kind of like the proposed, ways it works. 00:13:13.533 --> 00:13:17.133 So, one is that it forms a carbon centered, free radical, 00:13:17.400 --> 00:13:20.666 and it kills the parasite through damage to the lipid and vacuole membranes. 00:13:21.333 --> 00:13:25.133 Another is that it basically just inactivates inactivates 00:13:25.133 --> 00:13:27.333 the Plasmodium proteins. 00:13:27.333 --> 00:13:30.333 A third mechanism is that, 00:13:30.466 --> 00:13:31.800 it will basically interfere 00:13:31.800 --> 00:13:34.800 at the conversion of heme attend to human zone. 00:13:35.333 --> 00:13:38.133 And when you get this buildup of human sending the protozoa 00:13:38.133 --> 00:13:40.400 and it's toxic to them. 00:13:40.400 --> 00:13:41.866 And then, 00:13:41.866 --> 00:13:44.066 what's known for sure is that our testing 00:13:44.066 --> 00:13:47.066 it induces a splenic process called pitting. 00:13:47.066 --> 00:13:51.666 And this is, basically you'll get rings of, dead parasites that are exposed to 00:13:51.666 --> 00:13:55.533 that are testing, and then they're consequently expelled from their host RBCs. 00:13:56.600 --> 00:13:59.466 And, after they're expelled 00:13:59.466 --> 00:14:02.600 from the RBCs, instead of being advised to, they're resealed. 00:14:03.600 --> 00:14:05.866 But you can imagine, like, during this 00:14:05.866 --> 00:14:08.866 process, that they'll be altered in some way. 00:14:09.066 --> 00:14:12.066 So they're not, like, perfectly healthy or through sites anymore. 00:14:12.600 --> 00:14:15.133 And they do, in fact return to the circulation. 00:14:15.133 --> 00:14:18.133 But they have, a rough like, 00:14:19.733 --> 00:14:22.733 close to 9% reduction in their surface area. 00:14:23.000 --> 00:14:24.333 And this makes them more fragile. 00:14:24.333 --> 00:14:27.000 So they end up having shorter half lives. 00:14:27.000 --> 00:14:32.066 So basically, all these infected cells undergo this process of, pitting 00:14:32.066 --> 00:14:35.066 and they become known as once infected repair sites. 00:14:35.533 --> 00:14:38.533 And then, at that point, they're essentially a time bombs, 00:14:38.666 --> 00:14:40.533 in the sense that they have a shortened half life. 00:14:40.533 --> 00:14:45.600 And the law kind of like, start penalizing, around the same time as one another. 00:14:46.666 --> 00:14:48.333 So post our testing, a delay at home. 00:14:48.333 --> 00:14:52.800 All this occurs after resolution of the malaria related symptoms. 00:14:52.800 --> 00:14:58.466 And it's basically going to occur, like days after the parasite clearance. 00:14:58.466 --> 00:15:02.266 So it's not directly related to the active infection process 00:15:02.266 --> 00:15:05.266 or to the presence of parasites themselves. 00:15:06.800 --> 00:15:09.666 There's been a couple like, 00:15:09.666 --> 00:15:12.666 I guess like smaller studies on this process. 00:15:13.533 --> 00:15:16.400 But, the, the kind of consensus among them 00:15:16.400 --> 00:15:19.400 is that, roughly after a week, 00:15:19.466 --> 00:15:22.866 of pitting like 20 to 25% of patients 00:15:22.866 --> 00:15:25.866 will experience this known delay from all this. 00:15:26.866 --> 00:15:30.066 And there's a small study kind of published in the journal blood 00:15:30.066 --> 00:15:33.200 in 2014 that looked at 123 travelers. 00:15:34.200 --> 00:15:36.266 And they found that 60% 00:15:36.266 --> 00:15:38.666 of these travelers ended up having, 00:15:38.666 --> 00:15:41.666 delayed hemolysis after or testing that treatment. 00:15:42.600 --> 00:15:47.266 And those sorry, that 60% of the ones 00:15:47.266 --> 00:15:51.000 who developed the post of late them also ended up needing transfusion. 00:15:51.666 --> 00:15:54.000 But basically 100% of them survived. 00:15:54.000 --> 00:15:58.066 So there's been, emphasis placed on this like, 00:16:00.133 --> 00:16:00.600 period of 00:16:00.600 --> 00:16:03.600 monitoring after treatment for or testing for, 00:16:03.800 --> 00:16:08.066 like just being at home also labs or basically, a month afterwards, 00:16:08.600 --> 00:16:12.800 knowing that the late hemolysis typically occurs like 1 or 2 weeks after. 00:16:12.800 --> 00:16:15.333 And then you can kind of say that they're in the clear, 00:16:15.333 --> 00:16:17.866 you know, that this process isn't going to kill the patient, 00:16:17.866 --> 00:16:21.266 but they, could very well likely need supportive treatment. 00:16:22.600 --> 00:16:24.933 And then, the second, 00:16:24.933 --> 00:16:28.733 kind of combination, medication that this patient was on 00:16:29.466 --> 00:16:32.466 is, known by the brand name quantum. 00:16:32.866 --> 00:16:36.933 And so the two, medications that it's composed of are, 00:16:37.800 --> 00:16:42.000 Artemis ether, which is also an artemisinin derivative. 00:16:42.000 --> 00:16:45.066 And then the my fan channel, which is, one. 00:16:47.600 --> 00:16:49.000 Sorry. 00:16:49.000 --> 00:16:52.000 And then so, Luma fan train as a kind of line. 00:16:52.066 --> 00:16:55.466 So it's going to target the conversion of humans and taking the zone as well. 00:16:55.866 --> 00:17:00.133 And, similarly, this will cause the toxic build up, mentioned in the parasite. 00:17:01.000 --> 00:17:04.000 So interestingly enough, 00:17:04.266 --> 00:17:07.466 chloroquine operates by the same mechanism, but 00:17:08.066 --> 00:17:13.333 he also has developed this, kind of evolutionary, escape mechanism where 00:17:13.333 --> 00:17:18.000 they have developed, a pump that's going to pump the chloroquine out of, 00:17:19.266 --> 00:17:20.266 that's all basically. 00:17:20.266 --> 00:17:22.066 So they don't allow that toxic build up. 00:17:22.066 --> 00:17:25.066 So, that'd be one of those cases of that, 00:17:26.200 --> 00:17:29.200 the treatment resistant kind of malaria popping up. 00:17:29.600 --> 00:17:32.600 And what else here? 00:17:33.533 --> 00:17:36.200 And then, kind of just like different, 00:17:36.200 --> 00:17:40.200 there's, there's harder to find kind of studies on this. 00:17:40.200 --> 00:17:43.200 There's just a couple of smaller case reports, 00:17:43.733 --> 00:17:45.600 and this one was basically showing 00:17:45.600 --> 00:17:49.600 that the hemolysis peaked 11 to 16 days after the, initiation. 00:17:49.600 --> 00:17:52.533 So, similar timeframe to the our test. 00:17:52.533 --> 00:17:56.400 And it had basically these are just graphs for the two patients. 00:17:56.866 --> 00:17:59.866 The top, graph is going to show 00:17:59.866 --> 00:18:03.200 their kind of hemoglobin over the course of those two weeks. 00:18:03.200 --> 00:18:05.600 And then the bottom is going to show, 00:18:05.600 --> 00:18:07.200 your LDH and your T ability. 00:18:07.200 --> 00:18:10.200 So the bottom is kind of monitoring, about this. 00:18:10.200 --> 00:18:12.600 While the top is monitoring, anemia. 00:18:14.066 --> 00:18:17.533 And. Kind 00:18:17.533 --> 00:18:21.266 of, going back to the patient here, this is, a screenshot 00:18:21.266 --> 00:18:25.600 of kind of how they were, but their skin type indicator shine 00:18:26.066 --> 00:18:29.333 and then as well as, like, basically their models as labs. 00:18:29.600 --> 00:18:32.600 So you can see, 00:18:32.933 --> 00:18:34.666 when he presented, he had a, 00:18:34.666 --> 00:18:38.000 he's pretty, severely anemic at 5.1. 00:18:38.000 --> 00:18:40.666 And then we basically just gave him supportive treatment. 00:18:40.666 --> 00:18:44.066 He ended up using, I think, five units of RBCs over his, 00:18:44.866 --> 00:18:48.000 three days, and then, his hemoglobin stabilized. 00:18:48.400 --> 00:18:51.400 He was also on, high dose steroids, 00:18:52.466 --> 00:18:55.466 in support of, his condition here. 00:18:55.533 --> 00:18:58.733 And looking at the have to go again, that was undetectable, as you would 00:18:58.733 --> 00:19:01.800 imagine with small says the t, Billy initially 00:19:01.800 --> 00:19:04.800 showed up kind of similar to, 00:19:05.066 --> 00:19:07.800 what you see in this case report over here. 00:19:07.800 --> 00:19:12.066 And then lactate dehydrogenase was, off the charts. 00:19:12.066 --> 00:19:15.066 Basically, his platelets remained normal of all time. 00:19:15.533 --> 00:19:17.933 And then his reticular sites were, 00:19:17.933 --> 00:19:20.333 very elevated, which showed he had an appropriate, 00:19:21.466 --> 00:19:24.466 like, EPO response. 00:19:24.666 --> 00:19:27.200 And looking at his, 00:19:27.200 --> 00:19:30.000 screen, his antibody screen came back negative. 00:19:30.000 --> 00:19:33.533 But he did have a positive and a negative evolution. 00:19:35.666 --> 00:19:38.066 So I bring these up because even though there was like, 00:19:38.066 --> 00:19:42.200 no literature of our testing and our team, 00:19:43.333 --> 00:19:47.066 some authors, they were still considering everything or not. 00:19:47.066 --> 00:19:49.400 Everything, other things on their differential. 00:19:49.400 --> 00:19:53.066 So, a warm autoantibody was identified and saw as okay, 00:19:53.066 --> 00:19:55.200 so the team was considering a primary one. 00:19:55.200 --> 00:19:58.000 I don't mean hemolytic anemia. 00:19:58.000 --> 00:20:00.800 Given the positive test and the setting of anemia, 00:20:00.800 --> 00:20:03.800 and then that would have been supported by their indirect 00:20:03.800 --> 00:20:06.800 hyperbola ribbon Amia, 00:20:07.266 --> 00:20:09.866 and then they were also considering 00:20:09.866 --> 00:20:12.866 a micro and geographic hemolytic anemia, 00:20:12.933 --> 00:20:15.933 something like TTP h u s or gi c, 00:20:16.000 --> 00:20:18.800 but it was lower on the differential since the platelet count 00:20:18.800 --> 00:20:21.800 was normal the whole time, there were no signs of mucosal bleeding. 00:20:22.333 --> 00:20:26.400 And then, lastly they considered under protect under production. 00:20:26.400 --> 00:20:29.933 But as I showed you, a patient was protecting appropriately. 00:20:30.600 --> 00:20:31.466 So those are all kind of 00:20:32.666 --> 00:20:34.266 pulled out and, 00:20:34.266 --> 00:20:39.600 yeah, basically a patient was diagnosed with ADHD and then the party and, 00:20:40.333 --> 00:20:43.000 had an uneventful stay, essentially, and discharged from that. 00:20:43.000 --> 00:20:46.000 But here's my references. 00:20:46.666 --> 00:20:47.866 Happy to take any questions.