WEBVTT 00:00:14.030 --> 00:00:16.316 we're going to talk a little bit about malaria. 00:00:16.316 --> 00:00:20.637 You've already had some, talks by, sand on parasites. 00:00:21.388 --> 00:00:24.391 So this is one of the great parasites of the world 00:00:24.541 --> 00:00:27.827 and, an important part of of the world. 00:00:27.827 --> 00:00:30.830 If we look at, this list of, 00:00:30.947 --> 00:00:34.734 diseases of infectious diseases in the world. 00:00:35.251 --> 00:00:40.590 About one fifth of all deaths in the world now are still due to infections. 00:00:41.124 --> 00:00:45.662 And if you look at this list, you can see that there's some well known things. 00:00:45.662 --> 00:00:49.532 So pneumonia, HIV Aids, gastroenterology, 00:00:49.766 --> 00:00:53.453 gastroenteritis, tuberculosis and malaria. 00:00:53.453 --> 00:00:56.489 Then in the year two, 2002 00:00:56.790 --> 00:00:59.576 was accounted for a little over 00:00:59.576 --> 00:01:03.146 a million and a quarter, deaths in the world. 00:01:03.830 --> 00:01:06.833 Most of those are young children or old people. 00:01:07.700 --> 00:01:09.719 And, but but it's 00:01:09.719 --> 00:01:12.722 very serious infectious disease. 00:01:12.772 --> 00:01:18.528 If you look down here at the bottom, by 2013, there's still a lot of cases. 00:01:18.561 --> 00:01:23.583 So back in 2002, there were 600 million cases per year. 00:01:24.200 --> 00:01:28.254 Now we're down to 207 million cases per year. 00:01:28.555 --> 00:01:30.206 That's pretty good. 00:01:30.206 --> 00:01:33.393 And the death rate has gone from 1.27 00:01:33.693 --> 00:01:36.980 down to 627,000 deaths per year. 00:01:37.347 --> 00:01:39.182 So we're making some progress. 00:01:39.182 --> 00:01:43.436 This is one of the first times we've ever really made progress 00:01:43.436 --> 00:01:47.340 in decreasing the prevalence of malaria in the world. 00:01:48.441 --> 00:01:50.810 You probably can't see this very well, 00:01:50.810 --> 00:01:55.131 but this is a, from 2000, from 2010, 00:01:55.431 --> 00:01:59.219 looking at the countries where malaria takes place, 00:01:59.519 --> 00:02:02.422 there are 99 countries in the world 00:02:02.422 --> 00:02:06.059 that have an endemic focus of malaria. 00:02:06.893 --> 00:02:09.078 Of those, three of them 00:02:09.078 --> 00:02:12.182 then account for half of the malaria in the world. 00:02:12.182 --> 00:02:15.502 And if you can't read those, those three are Nigeria, 00:02:16.169 --> 00:02:20.190 the Democratic Republic of the Congo and Burkina Faso. 00:02:20.223 --> 00:02:23.393 So all all in western Africa. 00:02:24.811 --> 00:02:29.966 If you look, then there are 14 countries that make up 80%. 00:02:29.999 --> 00:02:33.887 So if we go up to 80%, 14 countries account for that. 00:02:34.170 --> 00:02:39.142 And Ghana is the last one where we do a lot of work in that group of 14. 00:02:39.659 --> 00:02:43.079 If you look at 98% of malaria, 00:02:43.313 --> 00:02:46.316 it occurs in approximately 35 00:02:46.533 --> 00:02:49.369 out of those 99 countries. 00:02:49.369 --> 00:02:53.690 So there there are a number of countries that have endemic focus 00:02:53.690 --> 00:02:57.093 that have made fantastic improvement in malaria. 00:02:57.260 --> 00:03:01.014 There are still some really serious countries up here 00:03:01.130 --> 00:03:04.133 where malaria is still a very serious problem. 00:03:04.200 --> 00:03:05.418 And one of those is Ghana. 00:03:05.418 --> 00:03:10.857 If you look at Ghana in 2011, outpatient visits, 40% 00:03:10.857 --> 00:03:15.812 of their outpatient visits to clinics were due to malaria. 00:03:16.129 --> 00:03:19.883 If you look at hospital admissions, a little over a third of all 00:03:19.883 --> 00:03:22.886 hospital admissions are for malaria. 00:03:22.969 --> 00:03:26.155 If you look at deaths, 18% of the deaths, 00:03:26.573 --> 00:03:31.194 if you look at percent of deaths in kids under five. 00:03:31.794 --> 00:03:35.298 29% of those are from malaria. 00:03:35.331 --> 00:03:38.935 Now, you just think what would happen if primary children's, 00:03:38.935 --> 00:03:43.740 if a third of all of our deaths of primary children were from a single disease? 00:03:44.007 --> 00:03:46.676 We would be so down on that. 00:03:46.676 --> 00:03:52.098 We would do everything possible to try and prevent that kind of of mortality. 00:03:52.615 --> 00:03:57.887 And then the place where we have really made progress is in the case fatality. 00:03:57.887 --> 00:04:02.208 So this of every hundred people, under 100 kids under five, 00:04:02.542 --> 00:04:07.130 that get malaria, only 1.2 of them are now dying. 00:04:07.163 --> 00:04:08.298 Now that's bad. 00:04:08.298 --> 00:04:12.318 If one out of 100 kids died from malaria, that's bad. 00:04:12.802 --> 00:04:15.989 But it used to be four out of 100. 00:04:16.256 --> 00:04:20.243 It used to be one out of 25 kids died from malaria. 00:04:20.610 --> 00:04:23.096 So we've made good progress. 00:04:23.096 --> 00:04:27.000 If you look at who's dying, it's kids like this little kid. 00:04:27.567 --> 00:04:30.003 These little kids, those are the people. 00:04:30.003 --> 00:04:30.770 This is a village. 00:04:30.770 --> 00:04:33.439 We were working in in Ghana. 00:04:33.439 --> 00:04:35.992 The kids there are the are really 00:04:35.992 --> 00:04:39.145 the people at risk for dying from malaria. 00:04:40.797 --> 00:04:43.900 So let's go talk a little bit about the history of malaria. 00:04:43.916 --> 00:04:48.438 So we've had descriptions of malaria both in China and Europe for a long time. 00:04:48.805 --> 00:04:52.976 The Greeks used to have a disease that they called periodic fevers 00:04:52.976 --> 00:04:54.560 and spleen on magli. 00:04:54.560 --> 00:04:58.648 That meant that that these fevers came back every 2 or 3 days. 00:04:58.798 --> 00:05:01.801 And these people developed big spleens. 00:05:02.302 --> 00:05:04.037 We think that was malaria. 00:05:04.037 --> 00:05:07.073 They found that they could decrease 00:05:07.073 --> 00:05:10.293 the risk of that disease by draining swamps. 00:05:10.560 --> 00:05:13.563 They thought the swamps caused malaria. 00:05:13.863 --> 00:05:15.381 It wasn't the swamps. 00:05:15.381 --> 00:05:18.384 It was the mosquitoes that were, 00:05:19.202 --> 00:05:22.188 that were in the swamps that caused malaria. 00:05:22.255 --> 00:05:24.657 And then in the 1700s, 00:05:24.657 --> 00:05:29.178 people, from Europe that ended up in Peru found that people in Peru 00:05:29.212 --> 00:05:32.782 used to chew the bark of this queen of queen, a tree. 00:05:33.349 --> 00:05:35.968 And, and that 00:05:35.968 --> 00:05:38.971 and they used it for whenever they got fever. 00:05:38.988 --> 00:05:43.042 Well, it wasn't very good for most fevers, but it treated malaria. 00:05:43.860 --> 00:05:46.462 So this was a treatment of malaria. 00:05:46.462 --> 00:05:51.300 And eventually in the mid 1800s, we found out that was quinine. 00:05:51.417 --> 00:05:53.252 So almost all the patent, 00:05:54.537 --> 00:05:57.623 medicines of the 1800s had quinine in them. 00:05:57.774 --> 00:06:00.777 We even put quinine in soda water, 00:06:00.860 --> 00:06:03.663 thinking that it would make it make us healthier. 00:06:03.663 --> 00:06:06.449 Well, it probably doesn't make us healthier, but it 00:06:06.449 --> 00:06:07.850 but it does treat malaria. 00:06:07.850 --> 00:06:11.070 So many of the of the of the explorers 00:06:11.070 --> 00:06:14.057 that went to Africa carried this bark with them. 00:06:14.157 --> 00:06:17.543 And when they got malaria in Africa, they would treat themselves 00:06:17.777 --> 00:06:20.613 with the bark of this tree. 00:06:20.613 --> 00:06:23.549 Well, we eventually, 00:06:23.549 --> 00:06:26.302 we eventually were able to, 00:06:26.302 --> 00:06:29.439 produce that and, and find 00:06:29.672 --> 00:06:33.025 better medicines and tune, tree bark. 00:06:34.610 --> 00:06:38.147 So, in 1891, then, 00:06:39.182 --> 00:06:43.653 a man by the name of Ross discovered that or proved 00:06:43.653 --> 00:06:47.390 that malaria was spread by, mosquitoes. 00:06:47.790 --> 00:06:50.426 So now we we know about why 00:06:50.426 --> 00:06:53.780 the Greeks drained their swamps and the incidence went down. 00:06:54.147 --> 00:06:57.834 If mosquitoes are carrying this and we can decrease the mosquito 00:06:57.834 --> 00:07:02.488 population, then we can decrease the prevalence of this disease. 00:07:02.989 --> 00:07:05.191 So in 1902, Ross got the, 00:07:06.242 --> 00:07:08.060 he got the Nobel Peace, 00:07:08.060 --> 00:07:12.298 Nobel Prize for describing the malaria, life cycle. 00:07:12.298 --> 00:07:14.901 And we'll go over that in just a minute. 00:07:14.901 --> 00:07:16.769 And then, 00:07:16.769 --> 00:07:18.771 and, but even then, 00:07:18.771 --> 00:07:21.774 we didn't know where malaria went. 00:07:21.808 --> 00:07:25.261 So, so when the mosquito after the mosquito bites you, 00:07:26.662 --> 00:07:31.217 you may have 1 to 4, four weeks before you get sick 00:07:31.217 --> 00:07:34.554 or in some cases, a number of months after it before you get sick. 00:07:34.587 --> 00:07:39.442 So we didn't know where the malaria organism went until 1948, 00:07:39.625 --> 00:07:42.662 when they discovered that it hit out in the liver. 00:07:42.895 --> 00:07:46.682 So it's ho there's a liver phase of this life 00:07:46.682 --> 00:07:50.369 cycle that we that Ross didn't they didn't discover. 00:07:52.171 --> 00:07:55.341 So in the United States, we had malaria 00:07:55.591 --> 00:07:58.377 all over, all across the United States, from the East coast 00:07:58.377 --> 00:07:59.512 clear to the Rocky Mountains 00:07:59.512 --> 00:08:03.299 and some and a focus of malaria in Southern California. 00:08:04.217 --> 00:08:06.302 With time, we were able 00:08:06.302 --> 00:08:09.288 to decrease that amount of malaria, 00:08:09.655 --> 00:08:12.658 down to just the southern part of the United States. 00:08:12.959 --> 00:08:15.628 And in 1948, we eradicated 00:08:15.628 --> 00:08:19.649 malaria completely from from the U.S., and we did it 00:08:19.649 --> 00:08:24.504 by using a medicine called chloroquine that was better than quinine. 00:08:24.921 --> 00:08:28.157 We used it by draining swamps like the Greeks did. 00:08:29.158 --> 00:08:32.161 And we used it by spraying DDT 00:08:32.361 --> 00:08:36.415 in our homes and, and in places to get rid of mosquitoes. 00:08:37.166 --> 00:08:38.417 And and we did this. 00:08:38.417 --> 00:08:44.090 And in two years time, we eradicated malaria from the United States. 00:08:44.156 --> 00:08:45.841 Europe did the same thing. 00:08:45.841 --> 00:08:48.144 Southern Brazil did the same thing. 00:08:48.144 --> 00:08:50.329 So the World Health Organization said, 00:08:50.329 --> 00:08:53.449 hey, if they can do it, why can't we do it throughout the whole world? 00:08:53.783 --> 00:08:59.388 So they started eradication program in 1955, and they did the same things. 00:08:59.722 --> 00:09:02.091 They used DDT to kill mosquitoes. 00:09:02.091 --> 00:09:03.709 They drained swamps, 00:09:03.709 --> 00:09:06.712 and if they couldn't drain them, they covered the top with oil. 00:09:07.230 --> 00:09:10.233 And, they used chloroquine to, 00:09:10.283 --> 00:09:13.286 treat and prevent malaria. 00:09:14.120 --> 00:09:16.973 By 1976, 00:09:16.973 --> 00:09:20.409 that that was declared an absolute failure. 00:09:20.426 --> 00:09:23.429 And it failed for for all three reasons. 00:09:23.913 --> 00:09:26.699 Number one is that the, 00:09:26.699 --> 00:09:30.620 malaria became more resistant to chloroquine, so it didn't work as well. 00:09:31.037 --> 00:09:33.656 We found that DDT not only killed mosquitoes, but 00:09:33.656 --> 00:09:38.811 it killed a lot of other animals up the, the chance of of, of, 00:09:40.196 --> 00:09:41.480 the food chain. 00:09:41.480 --> 00:09:44.900 And so we couldn't really use DDT 00:09:44.900 --> 00:09:48.354 very safely and, putting oil over, 00:09:48.888 --> 00:09:52.408 over, water also destroyed a lot of plant life. 00:09:53.009 --> 00:09:56.963 So in 1976, they stopped the program. 00:09:57.830 --> 00:10:02.551 By the mid-nineties, malaria and all mosquito borne diseases 00:10:02.551 --> 00:10:06.355 had become more prevalent because the mosquito 00:10:06.355 --> 00:10:10.409 population of the world had had, increased so much. 00:10:11.761 --> 00:10:15.381 So that's kind of the history of of malaria. 00:10:16.832 --> 00:10:21.470 We if we look at the classification, it belongs to the kingdom Protista. 00:10:21.804 --> 00:10:27.209 It becomes, belongs to the class for Bahasa, the Speranza class. 00:10:27.476 --> 00:10:32.965 And this kingdom is the class that has sexual reproduction. 00:10:33.149 --> 00:10:38.421 So even these one celled organisms are able to, at times 00:10:38.604 --> 00:10:41.607 produced by combining DNA. 00:10:41.757 --> 00:10:45.478 And so malaria is one of those malaria is a spores 00:10:45.478 --> 00:10:49.432 or that has a sexual reproduction phase. 00:10:50.282 --> 00:10:52.585 The genus is Plasmodium 00:10:52.585 --> 00:10:57.990 and the species for humans is falciparum vivax or valley and malaria. 00:10:58.307 --> 00:11:02.628 So we have four species of malaria that are the human malaria. 00:11:03.212 --> 00:11:04.830 Now there are a whole bunch of other 00:11:04.830 --> 00:11:08.634 malaria is that infect monkeys and rodents and birds and reptiles. 00:11:09.001 --> 00:11:11.070 All of them have their own species. 00:11:11.070 --> 00:11:16.075 And usually there isn't a cross, transfer from other animals to us. 00:11:16.292 --> 00:11:19.729 Recently, there's a fifth, malaria 00:11:19.729 --> 00:11:25.017 species of monkeys that we now, see more commonly in humans. 00:11:25.017 --> 00:11:26.302 But that's quite unusual. 00:11:26.302 --> 00:11:29.638 So we're going to just cover these four species. 00:11:29.905 --> 00:11:32.425 And that's what we'll talk about today. 00:11:32.425 --> 00:11:35.428 Now, in in parasites, 00:11:36.145 --> 00:11:38.964 the definitive host is the host 00:11:38.964 --> 00:11:41.967 where sexual reproduction takes place 00:11:42.051 --> 00:11:45.321 and the intermediate host has reproduction. 00:11:45.438 --> 00:11:50.493 But it's more just cell division, not sexual reproduction. 00:11:50.943 --> 00:11:54.413 And the definitive host for malaria is the mosquito. 00:11:54.747 --> 00:11:57.750 So that's where the sexual reproduction takes place. 00:11:57.767 --> 00:12:02.838 All of all of the reproduction in humans is just from plain cell division. 00:12:04.073 --> 00:12:06.175 So here's the here's the life cycle. 00:12:06.175 --> 00:12:09.812 This is really, more complicated than you ever want to believe. 00:12:10.162 --> 00:12:12.898 But there are there are, there are three 00:12:12.898 --> 00:12:15.901 main areas there and here. 00:12:16.051 --> 00:12:17.820 And here's the mosquito. 00:12:17.820 --> 00:12:21.407 So the mosquito picks up the gamete of sites. 00:12:21.690 --> 00:12:25.461 So by this time there's a male a male and a female gamete a site. 00:12:26.162 --> 00:12:27.830 The mosquito picks those up. 00:12:27.830 --> 00:12:31.917 They combine to find to, form analysis 00:12:32.251 --> 00:12:35.454 and, develop them into spores 00:12:35.454 --> 00:12:39.892 or that migrate to the, to the mouse organisms of the mosquito. 00:12:40.226 --> 00:12:43.229 And when the mosquito then bites a new host, 00:12:43.462 --> 00:12:46.982 it can transfer these spores or into the, 00:12:47.716 --> 00:12:50.719 human being within 30 minutes. 00:12:51.120 --> 00:12:55.007 Those spores, all my, all are transferred 00:12:55.007 --> 00:12:58.227 from the skin to the bloodstream to the liver. 00:12:58.644 --> 00:13:03.983 And they're they they can either start multiplying immediately 00:13:04.400 --> 00:13:08.521 and, and produce a whole, group of, 00:13:10.172 --> 00:13:13.526 ring organisms, or they can sit there 00:13:13.642 --> 00:13:18.564 for a number of months inactive, not causing any trouble. 00:13:19.048 --> 00:13:22.401 During this time, there are no symptoms. Yes. 00:13:27.573 --> 00:13:28.524 They get there. 00:13:28.524 --> 00:13:31.527 The question is, do they use the, 00:13:32.311 --> 00:13:33.863 hepatic portal system? 00:13:33.863 --> 00:13:35.214 They are in the blood. 00:13:35.214 --> 00:13:37.233 They're in the total bloodstream. 00:13:37.233 --> 00:13:40.352 So? So part of them, as they move through the liver, 00:13:40.586 --> 00:13:44.390 they attach to the liver, and then they invade the liver. So? 00:13:45.541 --> 00:13:48.410 So they, 00:13:48.410 --> 00:13:53.399 they then, can sit there or they can start dividing immediately 00:13:53.399 --> 00:13:56.785 the fastest they can go from the liver to, to. 00:13:56.785 --> 00:13:58.671 This is seven days. 00:13:58.671 --> 00:14:02.458 So the incubation time then is, is 00:14:02.458 --> 00:14:05.911 the very fastest can be seven days after the mosquito bite. 00:14:07.079 --> 00:14:08.998 The average is two weeks. 00:14:08.998 --> 00:14:11.717 And usually within four weeks. 00:14:11.717 --> 00:14:15.838 The ones that start dividing right away have all matured to the point, 00:14:16.488 --> 00:14:19.525 where they, developed the ring forms 00:14:19.525 --> 00:14:22.528 and, and and, and go into the red cell. 00:14:22.912 --> 00:14:26.899 Once they're in the red cell, then we begin to become symptomatic. 00:14:27.233 --> 00:14:27.867 So for. 00:14:30.753 --> 00:14:32.071 We have no symptoms at all. 00:14:32.071 --> 00:14:35.057 While all of this is taking place in our liver. 00:14:35.958 --> 00:14:39.812 Once they invade the, the, red cell, 00:14:40.379 --> 00:14:43.732 here's the little ring form that you can see in the in the red cell. 00:14:44.600 --> 00:14:48.537 And, then it begins to mature and develop cytoplasm. 00:14:48.837 --> 00:14:51.840 Then then it begins to divide 00:14:51.840 --> 00:14:54.710 and form new Marzo, Mesozoic. 00:14:54.710 --> 00:14:57.663 And then it ruptures the red blood cell. 00:14:57.663 --> 00:15:01.700 The numerous the whites then go into new red blood cells. 00:15:01.917 --> 00:15:05.154 And this this, cycle is repeated 00:15:05.487 --> 00:15:08.307 for some reason that we don't understand yet. 00:15:08.307 --> 00:15:11.810 Some of these sites, instead of forming trophies, 00:15:11.827 --> 00:15:14.830 whites develop into gamete sites 00:15:14.880 --> 00:15:18.717 and prepare themselves to be taken up by the mosquito 00:15:19.018 --> 00:15:22.021 to complete the life cycle. 00:15:22.321 --> 00:15:24.590 Now, this this system here 00:15:24.590 --> 00:15:28.127 synchronizes so that almost all of this happens, 00:15:29.094 --> 00:15:30.145 together. 00:15:30.145 --> 00:15:34.950 And when it happens together, then we develop the acute symptoms of malaria. 00:15:35.267 --> 00:15:36.502 And then while it's. 00:15:36.502 --> 00:15:40.623 And then when it invades the new red blood cells and while it's developing 00:15:40.623 --> 00:15:45.227 for about 48 to 72 hours, we become better again. 00:15:45.477 --> 00:15:49.048 The symptoms disappear, and then we develop the fever again. 00:15:49.048 --> 00:15:53.719 When this happens a second time and a third time, that's where we get 00:15:53.719 --> 00:15:57.089 the periodic fever that we talked about, that the Greeks, 00:15:57.239 --> 00:16:00.242 the Greeks described. 00:16:00.509 --> 00:16:00.960 All right. 00:16:00.960 --> 00:16:05.180 So let's talk about, a patient then with Alsip for malaria. 00:16:05.197 --> 00:16:08.200 So this is Plasmodium falciparum. 00:16:08.300 --> 00:16:11.754 This is the most important malaria that we study 00:16:11.987 --> 00:16:16.759 because 98% of all deaths are from this, 00:16:17.276 --> 00:16:20.095 this species of of malaria. 00:16:20.095 --> 00:16:24.266 So this is a patient that we saw, here at the VA hospital, 00:16:25.234 --> 00:16:28.320 a 52 year old male, he had gone to gone to Africa. 00:16:28.704 --> 00:16:31.523 He had had he not taking any medicine to prevent 00:16:31.523 --> 00:16:34.526 malaria like we're supposed to, if we've never had malaria. 00:16:35.477 --> 00:16:39.982 He came back to Montana, about a week after he got home. 00:16:39.982 --> 00:16:44.636 He started having, chills and fever and sweats, 00:16:44.820 --> 00:16:48.407 and he called his doctor and he said, I'm sick. 00:16:48.407 --> 00:16:52.644 And his doctor said, we'll take this antibiotic and didn't even see him. 00:16:52.795 --> 00:16:58.517 Within 3 or 4 days, he was found unconscious and is in his, room. 00:16:58.884 --> 00:17:03.122 And, they put him on an airplane and sent him to Salt Lake City. 00:17:03.422 --> 00:17:07.009 By the time he arrived here, we knew that he had been in Ghana. 00:17:07.309 --> 00:17:11.747 And we knew that the most likely thing that he had was malaria. 00:17:12.181 --> 00:17:16.552 So we looked at a blood smear, and you can actually see these organisms 00:17:16.552 --> 00:17:18.771 in the blood smear. We'll show you that. 00:17:18.771 --> 00:17:23.342 And a one third, 30% of his blood, 00:17:24.059 --> 00:17:27.062 had the malaria organism in it. 00:17:27.062 --> 00:17:32.401 Now, if you think about that, that means that when that matures, this next cycle, 00:17:32.401 --> 00:17:36.088 then is going to destroy a third of his red blood cells. 00:17:36.505 --> 00:17:38.574 He was in serious, serious condition. 00:17:39.658 --> 00:17:42.811 So we, started him on medication. 00:17:42.811 --> 00:17:45.180 We treated him with an exchange transfusion 00:17:45.180 --> 00:17:49.051 a couple of times, and, we thought that was a good thing. 00:17:49.068 --> 00:17:53.605 And it may have been, but with better medicine that we have now, 00:17:53.789 --> 00:17:58.343 we have found that exchange transfusions probably aren't that much of a help. 00:17:58.877 --> 00:18:03.899 But after his first exchange, as is Paris, a team, he went down to 10%. 00:18:04.199 --> 00:18:07.319 After the second time, it went down to 1%. 00:18:07.736 --> 00:18:11.039 And, essentially his malaria had been treated. 00:18:11.273 --> 00:18:14.843 But the damage that it had caused was not treated. 00:18:15.060 --> 00:18:16.678 So what happened? 00:18:16.678 --> 00:18:20.999 He had, he was still in a coma, so he still had cerebral malaria. 00:18:20.999 --> 00:18:24.686 It took him two weeks to get him out of that malaria coma. 00:18:25.471 --> 00:18:28.257 His respiratory system, his lungs were not working, 00:18:28.257 --> 00:18:30.509 so we had him on a respirator. 00:18:30.509 --> 00:18:33.745 And it took three weeks before we could wind him off his respirator, 00:18:34.229 --> 00:18:36.932 and then his kidneys failed. 00:18:36.932 --> 00:18:38.934 And his kidneys, failed. 00:18:38.934 --> 00:18:43.105 And he required dialysis for six weeks, and then his kidneys recovered. 00:18:43.372 --> 00:18:47.176 So why why those three organ systems? 00:18:48.260 --> 00:18:51.063 We'll see in a minute what happens to the organ systems. 00:18:51.063 --> 00:18:55.317 But those three organ systems are more sensitive to the lack of oxygen 00:18:55.584 --> 00:18:57.870 than some of the other systems of the body. 00:18:57.870 --> 00:19:02.691 And so they're the ones that are most damaged, by a severe malaria. 00:19:02.691 --> 00:19:05.694 Like this man had. 00:19:06.228 --> 00:19:08.213 So let's talk about why 00:19:08.213 --> 00:19:12.351 this organism causes almost all of the deaths from malaria. 00:19:12.951 --> 00:19:16.021 And and the number one thing is it can invade 00:19:16.021 --> 00:19:19.007 all stages of red blood cells. 00:19:19.741 --> 00:19:23.779 So you think, you know, you think of red blood cells or red blood cells. 00:19:23.779 --> 00:19:27.683 But for malaria, red blood cells are new. 00:19:27.683 --> 00:19:30.769 Red blood cells that have just been produced from the bone marrow. 00:19:32.070 --> 00:19:36.959 All red blood cells or red blood cells at 90 days, 90 days. 00:19:36.959 --> 00:19:41.880 Most red blood cells then are, senescent, and they're destroyed by the 00:19:42.264 --> 00:19:43.232 by the spleen. 00:19:44.366 --> 00:19:46.218 Falciparum malaria has the 00:19:46.218 --> 00:19:50.072 ability to invade all stages of red blood cells. 00:19:50.272 --> 00:19:55.310 The young ones, the regular ones and the senescent ones. So? 00:19:55.644 --> 00:19:58.947 So the whole blood supply is open 00:19:59.214 --> 00:20:02.367 to invasion by malaria organisms. 00:20:03.168 --> 00:20:06.171 The second thing is once these 00:20:06.171 --> 00:20:08.957 once the malaria gets into the blood cell, 00:20:08.957 --> 00:20:13.111 it starts to digest the hemoglobin that's in the blood cell. 00:20:13.729 --> 00:20:17.216 And that's what it uses as an energy source for it 00:20:17.216 --> 00:20:21.620 to grow and divide and mature and continue its life cycle 00:20:22.371 --> 00:20:26.341 as it does that, as it as it does that, it produces 00:20:26.808 --> 00:20:30.028 malaria proteins that migrate 00:20:30.212 --> 00:20:33.115 to the surface of the red blood cell. 00:20:33.115 --> 00:20:35.701 Now, one of the amazing things in life 00:20:35.701 --> 00:20:41.423 is that that antigen, that malaria antigen on the surface of the red blood 00:20:41.423 --> 00:20:45.444 cell has a receptor site in our bodies, 00:20:45.861 --> 00:20:49.131 and that receptor site is in our small 00:20:49.131 --> 00:20:52.134 blood vessels, our capillary blood system, 00:20:52.284 --> 00:20:57.923 so that a red blood cell with a with an antigen on it can attach to the 00:20:57.923 --> 00:21:04.012 to our, vascular system and absolutely plug up our vascular system. 00:21:04.680 --> 00:21:07.950 So that's why we think it causes the damage 00:21:07.950 --> 00:21:11.637 to the brain and the lungs and the kidney if we destroy the blood. 00:21:11.637 --> 00:21:15.807 So if we destroy the flow of the blood cell by all of these things 00:21:15.807 --> 00:21:19.945 clogging up our blood vessels, that sweat really does 00:21:20.462 --> 00:21:25.350 the damage that results in, in our, severe illness. 00:21:26.702 --> 00:21:27.836 Now, this same thing 00:21:27.836 --> 00:21:30.839 then, can cause red cells to hook together 00:21:30.922 --> 00:21:33.925 and and cause plugging up of blood vessels. 00:21:34.376 --> 00:21:36.595 Or they can, 00:21:36.595 --> 00:21:38.880 they can actually agglutination together. 00:21:38.880 --> 00:21:43.135 So we think that's why this organism 00:21:43.135 --> 00:21:47.005 so, so number one is it can inhabit all red blood cells. 00:21:47.005 --> 00:21:52.794 So you get a huge parasite Mia number two is it can clog up the vascular system and 00:21:53.011 --> 00:21:56.515 and and damage our organs. 00:21:58.050 --> 00:22:02.037 So this is an artist's rendition of, What? 00:22:02.087 --> 00:22:04.473 Plasmodium falciparum. 00:22:04.473 --> 00:22:08.060 Looks like you can see, uninfected red blood cell. 00:22:08.060 --> 00:22:11.963 You can see the ring form, you can see the Mesozoic ring form, 00:22:11.963 --> 00:22:16.768 then begin to form cytoplasm and develop into a trophy 00:22:16.768 --> 00:22:23.091 Zoid that trophies right then begins to divide, and you get numerous 00:22:23.091 --> 00:22:27.896 the lights that go back up and invade the red blood cells again. 00:22:28.230 --> 00:22:32.567 If we were to look at a smear of one of these, 00:22:33.685 --> 00:22:35.837 of someone with falciparum malaria, 00:22:35.837 --> 00:22:41.360 we would see ring forms, and occasionally we would examine the sites 00:22:41.843 --> 00:22:44.846 and we wouldn't see any of this. 00:22:46.014 --> 00:22:49.017 And the reason would 00:22:49.201 --> 00:22:51.236 is because these the 00:22:51.236 --> 00:22:55.974 this stage of the infection is all hung up in our vascular system. 00:22:57.092 --> 00:22:58.643 So we don't get to see it. 00:22:58.643 --> 00:23:02.931 We don't get to see all these other stages because it's all hooked 00:23:02.931 --> 00:23:04.649 into our vascular system. 00:23:04.649 --> 00:23:08.537 And living happily, waiting to destroy our next red blood cell cycle. 00:23:09.321 --> 00:23:13.742 What we do see then is the ring forms, before they start to attach 00:23:13.742 --> 00:23:16.945 to the vascular system, and we see the Mas 00:23:16.945 --> 00:23:19.948 or the, the, 00:23:20.482 --> 00:23:24.386 gamete sites, which are waiting for a mosquito 00:23:24.386 --> 00:23:27.539 to pick them up so they can complete the life cycle. 00:23:28.707 --> 00:23:30.709 Now, here we can see just a little better. 00:23:33.078 --> 00:23:36.231 In what, what we really see so frequently. 00:23:36.231 --> 00:23:39.234 There are so many mirror sites that we can see, 00:23:39.918 --> 00:23:43.622 infection where 2 or 3 of them get into the same red blood cell. 00:23:44.456 --> 00:23:47.459 So this is a huge infection. 00:23:48.093 --> 00:23:49.277 Here are the immediate sites. 00:23:49.277 --> 00:23:52.280 These are called banana shaped commuter sites. 00:23:52.280 --> 00:23:55.550 Even in these, if you look carefully, you can see 00:23:55.550 --> 00:23:58.553 that they are inside the red blood cell. 00:23:58.670 --> 00:24:02.207 And they just stretch out the red blood cell and continue 00:24:02.207 --> 00:24:05.510 to use the hemoglobin as a source of energy. 00:24:06.361 --> 00:24:09.347 Here's what they really look like under the microscope. 00:24:11.399 --> 00:24:13.819 So that's that's Plasmodium falciparum. 00:24:13.819 --> 00:24:16.221 Let's talk then a little bit about vivax. 00:24:16.221 --> 00:24:19.307 And obviously we're going to talk about them together 00:24:19.591 --> 00:24:23.628 because the two of them together really are so similar 00:24:23.912 --> 00:24:27.749 that that, that it's easy to, to, 00:24:27.749 --> 00:24:31.653 to learn everything about one and, and know what's happening with the other. 00:24:31.653 --> 00:24:35.207 There is one major difference that we'll talk about a little later. 00:24:35.724 --> 00:24:38.727 So this is a 27 year old female, 00:24:39.227 --> 00:24:42.047 she went to Kenya to help build schools. 00:24:42.047 --> 00:24:44.883 She took all of her medicine, preventive medicine, 00:24:44.883 --> 00:24:48.086 just like she was supposed to while she was there. 00:24:48.236 --> 00:24:50.155 And for four weeks later. 00:24:50.155 --> 00:24:52.974 So the medicine that we give doesn't work in the liver. 00:24:52.974 --> 00:24:57.896 So what we do is we keep them on it for weeks after, because if it breaks 00:24:57.896 --> 00:25:01.049 out of the liver into the red cells, then that medicine works. 00:25:01.383 --> 00:25:03.235 But it doesn't work in the liver. 00:25:03.235 --> 00:25:05.070 That's why these people are supposed 00:25:05.070 --> 00:25:08.540 to can't stay on their medicine for four weeks after they come back. 00:25:08.990 --> 00:25:09.741 She did that 00:25:11.276 --> 00:25:12.928 12 weeks later. 00:25:12.928 --> 00:25:15.564 So now we've gone and she took her medicine for four weeks. 00:25:15.564 --> 00:25:17.215 Now we're 12 weeks out. 00:25:17.215 --> 00:25:20.218 She developed chills, fever, 00:25:21.386 --> 00:25:25.257 at night, are sweating, headaches and muscle aches. 00:25:25.524 --> 00:25:28.910 And she went to the to the emergency room and told the doctor, 00:25:29.094 --> 00:25:31.279 I think I have malaria. 00:25:31.279 --> 00:25:34.616 And the doctor laughed at her and said, you can't have malaria. 00:25:34.950 --> 00:25:37.736 Malaria should happen within the first four weeks. 00:25:37.736 --> 00:25:41.006 Well, he forgot about this kind of malaria. 00:25:41.456 --> 00:25:45.010 So in this kind of malaria, either vivax or valley, 00:25:45.660 --> 00:25:48.947 the liver organism 00:25:48.947 --> 00:25:54.202 may not even divide for months or sometimes years. 00:25:54.502 --> 00:25:58.940 So it may sit there asymptomatic, no symptoms at all, 00:25:59.341 --> 00:26:04.796 and then break out and and cause disease months or years later. 00:26:04.796 --> 00:26:07.649 In this lady it was three months afterwards. 00:26:07.649 --> 00:26:10.218 What does this allow this organism to do? 00:26:10.218 --> 00:26:13.288 This allows this organism to go through a dry period 00:26:13.672 --> 00:26:18.476 or a winter period, and then break out the next time there mosquito is available. 00:26:18.627 --> 00:26:20.528 So this is more off this year. 00:26:20.528 --> 00:26:24.182 So you can see this in, in tropical countries. 00:26:24.349 --> 00:26:27.619 But if you look at temperate country countries, 00:26:27.802 --> 00:26:31.823 this is the malaria that can wait from one winter to the next. 00:26:32.340 --> 00:26:37.162 And so, you're more likely to see it in places like the United States. 00:26:38.330 --> 00:26:40.832 So anyway, she, she, 00:26:40.832 --> 00:26:45.870 the emergency doctor was smart enough that he ordered a, smear, 00:26:46.104 --> 00:26:48.857 and the malaria smear showed 1% 00:26:48.857 --> 00:26:51.860 parasitism here, not 30%. 00:26:51.893 --> 00:26:54.529 And they noticed that the red blood cells 00:26:54.529 --> 00:26:57.866 were larger than the non-infected red cells. 00:26:58.550 --> 00:27:02.604 That's what happens in immature red cells. 00:27:02.604 --> 00:27:05.123 Or we call those reticular sites. 00:27:05.123 --> 00:27:10.345 So the, about 3% of our blood can of our red blood 00:27:10.345 --> 00:27:13.882 cells can be new blood cells just released from the bone marrow. 00:27:14.132 --> 00:27:16.101 They're a little larger than usual. 00:27:16.101 --> 00:27:21.439 And it turns out that vivax and the valley have a very hard time 00:27:21.623 --> 00:27:26.478 getting into red blood cells after they've passed the reticular site phase. 00:27:27.662 --> 00:27:29.397 So that limits so. 00:27:29.397 --> 00:27:33.418 So it would be very hard for one of these organisms to cause 30% parasite. 00:27:33.418 --> 00:27:34.352 Damia. 00:27:34.352 --> 00:27:38.223 Usually, it's in the 1%, area. 00:27:39.541 --> 00:27:42.027 So they notice that they're notice 00:27:42.027 --> 00:27:45.947 that there's a stippling of the red blood cells called shifters dots. 00:27:45.947 --> 00:27:47.032 And the red blood cells. 00:27:47.032 --> 00:27:49.851 We'll we'll look at those, 00:27:49.851 --> 00:27:52.854 and, and then the final thing is 00:27:53.104 --> 00:27:57.242 these organisms don't have the capability of, 00:27:57.509 --> 00:28:00.445 of attaching to our vascular system. 00:28:00.445 --> 00:28:03.531 So we see the whole gamut of their life cycle. 00:28:03.531 --> 00:28:07.619 We see the Mercedes, we see the trophies, the lights, we see everything. 00:28:07.886 --> 00:28:11.122 Their whole life cycle when we look under the microscope. 00:28:11.906 --> 00:28:15.260 So this then patient can be treated 00:28:15.260 --> 00:28:18.263 with chloroquine on an outpatient basis. 00:28:18.413 --> 00:28:22.367 And then there is one single medicine 00:28:22.650 --> 00:28:27.272 that will kill the organisms that are left in the liver cells. 00:28:27.689 --> 00:28:31.009 So in this, this lady, she was treated with chloroquine 00:28:31.292 --> 00:28:34.312 that got rid of her acute red blood cell phase. 00:28:34.612 --> 00:28:39.768 And then she was treated with a medicine called primary one that killed these 00:28:39.901 --> 00:28:45.557 Hypnos whites or these sleeper cells that are in the liver that are left over. 00:28:45.557 --> 00:28:48.560 Otherwise, she could develop malaria again, 00:28:48.977 --> 00:28:51.262 another 3 or 4 months. 00:28:51.262 --> 00:28:54.682 So this is the artist's rendition of this organism. 00:28:55.550 --> 00:28:58.403 You can see again there the there the, 00:28:58.403 --> 00:29:01.673 ring forms, you can see the trophies, the lights. 00:29:02.123 --> 00:29:05.777 You can see this little stippling that we talked about in the red blood cell 00:29:05.777 --> 00:29:10.532 cytoplasm called shift nurse dots that are seen with both vivax 00:29:10.532 --> 00:29:13.651 and or valley. And if we looked at this 00:29:13.651 --> 00:29:16.855 at the microscope, we could see all of these develop, 00:29:18.423 --> 00:29:21.409 all the development phases of this life cycle. 00:29:21.443 --> 00:29:25.013 And then notice that, remember the banana shaped gamete of sites, 00:29:25.396 --> 00:29:28.383 these then are amoeba and me. 00:29:28.383 --> 00:29:32.637 Boyd gamete decides that the the mosquito takes up 00:29:32.987 --> 00:29:35.990 the complete the life cycle. 00:29:35.990 --> 00:29:38.693 So here you can see a little bit better. 00:29:38.693 --> 00:29:40.345 Here's a reticular site. 00:29:40.345 --> 00:29:44.933 You can see that this infected red blood cell is larger than the others. 00:29:44.933 --> 00:29:47.552 So we think it's a ridiculous site or a primitive, 00:29:47.552 --> 00:29:49.938 immature form of the red blood cells. 00:29:49.938 --> 00:29:51.022 A little harder to tell. 00:29:51.022 --> 00:29:55.193 And some of these others, you can see here, we can see the, 00:29:55.193 --> 00:29:58.196 the trophies, the white cytoplasm, 00:29:59.631 --> 00:30:02.784 and here we can see the skirts. 00:30:02.784 --> 00:30:04.219 These aren't, 00:30:04.219 --> 00:30:08.523 where they're getting ready to, to break open and infect new red blood cells. 00:30:08.873 --> 00:30:12.293 And then the gamete, a site, the amyloid gamete, a site. 00:30:13.711 --> 00:30:15.296 So the final, 00:30:15.296 --> 00:30:19.067 the final, species of Plasmodium 00:30:19.501 --> 00:30:22.487 is, Plasmodium malaria. 00:30:22.704 --> 00:30:26.841 It's, a very, fairly benign form of malaria. 00:30:27.775 --> 00:30:30.778 The best example of this was written up, 00:30:31.012 --> 00:30:36.301 when there was a 74 year old female born and lived in Greece her whole life. 00:30:36.651 --> 00:30:39.654 Greece also eradicated malaria, 00:30:40.255 --> 00:30:45.260 in the 50s and 60s, so that, we think this lady must have gotten 00:30:45.260 --> 00:30:49.397 malaria when she was a young girl and lived with it her whole life. 00:30:49.681 --> 00:30:53.218 She didn't ever recall acute chills, fever, or sweating. 00:30:53.635 --> 00:30:57.622 In 1995, however, she was found to have an enlarged spleen 00:30:58.072 --> 00:31:01.459 and the doctors taking care of her said, oh, we think you have lymphoma. 00:31:01.709 --> 00:31:05.547 And they started her on chemotherapy for the for lymphoma. 00:31:05.813 --> 00:31:09.067 And then she developed fever and chills and, 00:31:09.100 --> 00:31:14.339 and it was a cycle of every 72 hours she had fever and chills. 00:31:15.273 --> 00:31:17.091 Well they did some antibody testing. 00:31:17.091 --> 00:31:21.596 Found out she had antibody against, more, Plasmodium malaria. 00:31:21.963 --> 00:31:26.868 They were not able to see it on the reds on the under this, light microscope. 00:31:27.168 --> 00:31:29.387 But they were able to do some very fancy, 00:31:30.872 --> 00:31:32.240 antigen tests 00:31:32.240 --> 00:31:35.243 that showed that this was Plasmodium malaria. 00:31:35.627 --> 00:31:37.879 She was treated with chloroquine 00:31:37.879 --> 00:31:40.949 and her spinal magli resolved. 00:31:41.215 --> 00:31:43.735 And she didn't have really lymphoma. 00:31:43.735 --> 00:31:46.971 So in this case, this lady probably lived this 00:31:46.971 --> 00:31:50.008 with this fairly benign disease for years and years. 00:31:50.208 --> 00:31:53.061 And then after it was started on chemotherapy, 00:31:53.061 --> 00:31:56.064 it began to flare up and caused symptoms. 00:31:57.865 --> 00:32:01.669 Here's the blood stages of this again, the ring forms. 00:32:01.920 --> 00:32:07.342 You can see that the trough aside in this stage is usually called a band formed. 00:32:07.342 --> 00:32:09.827 So it looks a little different than the trough 00:32:09.827 --> 00:32:12.830 seen in the other two other three species. 00:32:13.014 --> 00:32:16.517 And again, you have amoeba, amyloid gamete sites. 00:32:17.485 --> 00:32:18.920 You can't tell really. 00:32:18.920 --> 00:32:22.173 Well here but also senescent red blood cells. 00:32:22.173 --> 00:32:26.778 So this this species cannot get into reticular sites. 00:32:27.061 --> 00:32:29.881 It cannot get into healthy red blood cells. 00:32:29.881 --> 00:32:32.817 It gets into senescent red blood cells 00:32:32.817 --> 00:32:35.987 that are almost ready to be destroyed by the spleen. 00:32:36.471 --> 00:32:39.474 Some of the, sometimes those are a little smaller. 00:32:39.540 --> 00:32:41.726 And you might be able to see that a little bit here. 00:32:41.726 --> 00:32:45.713 This is infected red blood cell, a little smaller than those around. 00:32:46.431 --> 00:32:50.601 So this has a this organism has a huge disadvantage. 00:32:50.868 --> 00:32:56.307 It really does not cause severe illness in in humans. 00:32:59.210 --> 00:33:00.228 Let's see, 00:33:00.228 --> 00:33:03.031 here's the van form of the 12 aside. 00:33:03.031 --> 00:33:04.916 Here's the, 00:33:04.916 --> 00:33:07.919 This guy isn't ready to break open and. 00:33:07.919 --> 00:33:08.486 Oops. 00:33:08.486 --> 00:33:11.489 And and here's the give me two sites. 00:33:11.606 --> 00:33:13.941 So those are the four species. 00:33:13.941 --> 00:33:15.560 Let's compare them just a little bit. 00:33:15.560 --> 00:33:18.296 There's some other things that we ought to know about. 00:33:18.296 --> 00:33:21.332 So we've already talked about why falciparum 00:33:21.749 --> 00:33:25.103 may be most plentiful in the tropics. 00:33:25.319 --> 00:33:29.090 Because it needs a constant continuous 00:33:29.307 --> 00:33:33.378 mosquito population to maintain itself in the environment, 00:33:33.711 --> 00:33:36.714 whereas vivax in know Valley have this 00:33:37.165 --> 00:33:39.684 hypno zoid in the liver that allows them 00:33:39.684 --> 00:33:43.738 to live in a more tropical or a subtropical country. 00:33:44.038 --> 00:33:48.292 And then this malaria that has chronic continuous infection 00:33:48.543 --> 00:33:52.130 can live in the tropics or in the or in the subtropics. 00:33:52.130 --> 00:33:54.932 Also. Now, we mentioned that, 00:33:55.883 --> 00:33:59.120 the malaria organism uses the 00:33:59.120 --> 00:34:02.640 hemoglobin of our red cells for its energy source. 00:34:03.241 --> 00:34:08.179 It turns out it has a harder time digesting hemoglobin. 00:34:08.479 --> 00:34:12.200 If we have an abnormal hemoglobin, what it likes is 00:34:12.417 --> 00:34:15.603 regular old hemoglobin that's in every healthy person. 00:34:15.987 --> 00:34:19.290 But if you have a disease like sickle cell disease, 00:34:19.607 --> 00:34:24.512 or if you have an abnormal hemoglobin, that's that hemoglobin CD3, 00:34:24.712 --> 00:34:28.583 or if you have a disease called thalassemia with an abnormal hemoglobin, 00:34:28.883 --> 00:34:31.886 or with one of these deficiencies in the hemoglobin, 00:34:32.220 --> 00:34:35.573 these then protect the person. 00:34:35.573 --> 00:34:39.777 So so these may cause the person to get sick from these things. 00:34:40.261 --> 00:34:43.247 But it protects the person from malaria. 00:34:43.614 --> 00:34:46.918 So if you go to West Africa like Ghana, 00:34:47.668 --> 00:34:51.172 approximately 15% of the population 00:34:51.172 --> 00:34:55.193 of West Ghana, of of West Africa and Ghana 00:34:56.160 --> 00:34:59.147 have sickle cell trait. 00:34:59.697 --> 00:35:02.400 And that means that a large population 00:35:02.400 --> 00:35:05.570 of their children have sickle cell disease. 00:35:05.570 --> 00:35:08.072 That's a serious disease. 00:35:08.072 --> 00:35:12.527 But with sickle cell trait, you're protected and you're more likely 00:35:12.527 --> 00:35:15.530 to live through a an infection of malaria 00:35:15.746 --> 00:35:18.749 than if you had normal hemoglobin. 00:35:19.066 --> 00:35:22.286 And that's that's somewhat true with all of these others. 00:35:22.587 --> 00:35:25.406 So there's a host resistance pattern 00:35:25.406 --> 00:35:29.727 that's protected some people from from malaria. 00:35:29.911 --> 00:35:34.882 And it's allowed the genes for these to become more prevalent 00:35:35.333 --> 00:35:38.419 in areas of the world where there is malaria. 00:35:40.938 --> 00:35:43.040 So the other thing we talked about, 00:35:43.040 --> 00:35:46.077 vivax and Valley, as if they're exactly the same. 00:35:46.277 --> 00:35:49.614 There is there are some differences, but the major difference 00:35:49.914 --> 00:35:53.601 is a difference with regards to Duffy antigen. 00:35:54.168 --> 00:35:58.322 So Duffy antigen is an antigen that we all have on our red blood cells. 00:35:58.639 --> 00:36:00.291 So that's not quite true. 00:36:00.291 --> 00:36:03.511 Some people have it on their red blood cells and some people don't. 00:36:04.078 --> 00:36:08.182 If we look at all of the rest of the world other than West Africa, 00:36:08.583 --> 00:36:11.569 the presence of Duffy antigen is 00:36:12.203 --> 00:36:15.206 has a prevalence of approximately 99%. 00:36:15.540 --> 00:36:20.361 So if we tested all of our blood and we tested it for Abo and RH 00:36:20.545 --> 00:36:25.399 and then tested it for Duffy antigen, almost all of us would have Duffy antigen. 00:36:26.817 --> 00:36:27.985 It turns out 00:36:27.985 --> 00:36:33.507 that vivax has to have Duffy antigen on the red blood cell, 00:36:33.708 --> 00:36:36.711 or it cannot infect the red blood cell. 00:36:37.261 --> 00:36:39.180 Isn't that interesting. 00:36:39.180 --> 00:36:41.883 So so vivax 00:36:41.883 --> 00:36:47.121 can only really exist in places in places where Duffy antigen is common. 00:36:47.572 --> 00:36:49.156 Where is that Duffy antigen. 00:36:49.156 --> 00:36:51.993 Not common in West Africa. 00:36:51.993 --> 00:36:54.745 In West Africa, the people with Duffy 00:36:54.745 --> 00:36:57.748 antigen have all been wiped out. 00:36:58.282 --> 00:37:00.718 And so they do not have Duffy antigen 00:37:00.718 --> 00:37:03.721 and they do not have vivax malaria. 00:37:04.188 --> 00:37:05.940 Now the difference between vivax 00:37:05.940 --> 00:37:09.176 and Novalee is a valley doesn't need Duffy antigen. 00:37:09.410 --> 00:37:12.647 It can get into red cells without Duffy antigen. 00:37:12.830 --> 00:37:17.101 So even though the two of them mimic each other this is one 00:37:17.101 --> 00:37:20.087 major difference. 00:37:21.022 --> 00:37:24.025 So, let's go on here. So, 00:37:25.076 --> 00:37:29.397 we've already talked about, falciparum giving get all red blood cells. 00:37:29.397 --> 00:37:32.183 Vivax in the valley only reticular sites. 00:37:32.183 --> 00:37:34.285 Malaria. Oh. Blood cells. 00:37:34.285 --> 00:37:37.338 The incubation time is generally two weeks 00:37:37.338 --> 00:37:40.341 for all of them from the time of the mosquito bite. 00:37:40.608 --> 00:37:45.413 But we just learned about the ability for hypnotize sites to stay, 00:37:46.697 --> 00:37:47.064 in the 00:37:47.064 --> 00:37:51.118 liver without any symptoms and without dividing for months 00:37:51.118 --> 00:37:55.039 or sometimes years after leaving the malaria area 00:37:55.323 --> 00:37:58.292 and then causing malaria. 00:37:58.292 --> 00:38:01.279 If we look at the number of marrows the whites in the liver, 00:38:01.762 --> 00:38:03.447 falciparum wins the battle. 00:38:03.447 --> 00:38:09.236 They can produce 40,000 of lights in a liver cell, in the liver 00:38:09.353 --> 00:38:12.957 and release them all at the same time into the bloodstream. 00:38:13.190 --> 00:38:14.909 So it already has an advantage. 00:38:14.909 --> 00:38:17.878 In addition to all the other advantages we've talked about. 00:38:17.878 --> 00:38:23.267 It has an advantage in that it starts with a much bigger load of merseyside's 00:38:23.517 --> 00:38:26.687 than with vivax or Valley or malaria. 00:38:27.571 --> 00:38:30.541 Same thing a little bit with the red cell cycle. 00:38:30.541 --> 00:38:34.278 So the red cell cycle can have 8 to 24 hours of lights 00:38:34.278 --> 00:38:38.449 per per red cell, some of the others much less. 00:38:39.050 --> 00:38:40.618 And then the periodicity. 00:38:40.618 --> 00:38:46.440 So usually once these, get synchronized, the first three all recur 00:38:46.440 --> 00:38:52.279 in about 48 hour cycles and malaria and 72 severity of attacks. 00:38:52.430 --> 00:38:57.201 It's really hard to tell when I see someone, with malaria. 00:38:57.468 --> 00:39:01.439 I can't tell clinically whether this is falciparum 00:39:01.672 --> 00:39:05.509 or vivax or Valley, because they're all the same. 00:39:05.509 --> 00:39:07.228 They all start out like the flu. 00:39:07.228 --> 00:39:09.146 You have headaches and muscle aches, 00:39:09.146 --> 00:39:12.600 and then you get a shaking chill and it's a bed shaking chill. 00:39:12.983 --> 00:39:15.353 It shakes your whole body. 00:39:15.353 --> 00:39:17.905 And it will that will last for about two hours. 00:39:17.905 --> 00:39:22.676 And then for about another 6 to 12 hours, you'll have a high fever. 00:39:22.910 --> 00:39:25.980 And then that will break and you'll develop a severe sweat, 00:39:26.213 --> 00:39:29.567 and then you'll get better and you'll think, oh, that wasn't so bad. 00:39:29.600 --> 00:39:32.787 Maybe I just had the the influenza or something. 00:39:33.421 --> 00:39:37.441 But if that recurs in at 48 hours, 00:39:37.892 --> 00:39:41.579 then you begin to think, oh, this could be malaria. 00:39:44.582 --> 00:39:47.568 Let's see, 00:39:48.419 --> 00:39:50.221 we've already talked. 00:39:50.221 --> 00:39:52.289 So we've already talked about most all the malaria. 00:39:52.289 --> 00:39:57.411 So the 1 to 5% of people who get falciparum die, very rare for anyone else. 00:39:57.745 --> 00:40:01.015 The latent infection is what we talk about with the hidden asides. 00:40:01.532 --> 00:40:04.702 The chronic persistence is what we talked about with malaria, 00:40:05.252 --> 00:40:06.537 the large red blood cells. 00:40:06.537 --> 00:40:09.323 We've already talked about stiffness docs. 00:40:09.323 --> 00:40:11.308 We've talked about, 00:40:11.308 --> 00:40:12.660 some of the other differences. 00:40:12.660 --> 00:40:15.780 Let's, let's, let's go on to diagnosis. 00:40:16.046 --> 00:40:20.818 So clinically, if you're in a malaria area or if you just came from a malaria 00:40:20.818 --> 00:40:24.205 and you develop chills, fever, sweats, headache and muscle 00:40:24.205 --> 00:40:27.208 aches, malaria has to be the top of the list. 00:40:27.258 --> 00:40:32.213 Most of the people in the world diagnosed this by taking a drop of blood 00:40:32.213 --> 00:40:36.600 and putting it on a slide, and then analyzing the red blood cells 00:40:36.600 --> 00:40:39.587 and just looking for the malaria organisms. 00:40:40.104 --> 00:40:44.425 So that's a pretty sensitive way to make this, make the diagnosis. 00:40:44.425 --> 00:40:46.043 And it's very inexpensive. 00:40:46.043 --> 00:40:49.346 All you need is a microscope, and somebody 00:40:49.346 --> 00:40:54.235 that's, that's, experienced in looking for these malaria organisms 00:40:54.535 --> 00:40:58.172 and that's how most of malaria is diagnosed now, 00:40:59.790 --> 00:41:01.158 there are other ways to do it. 00:41:01.158 --> 00:41:02.660 You can look at a thin smear. 00:41:02.660 --> 00:41:06.680 So the smears that we showed you today were all thin smears. 00:41:06.931 --> 00:41:11.569 So there you can look at so it has some advantage. 00:41:11.569 --> 00:41:13.771 You can do it much faster than the other. 00:41:13.771 --> 00:41:16.757 You can do it a couple of different stains. 00:41:16.941 --> 00:41:19.460 You can look at the red cell before morphology. 00:41:19.460 --> 00:41:23.280 So if you see large or small red cells, that may help 00:41:23.280 --> 00:41:26.750 you tell which malaria you that you're, you're looking at, 00:41:27.168 --> 00:41:32.423 the sensitivity is less because you don't have as many, organisms 00:41:32.673 --> 00:41:35.993 on a thin smear as you have on a, on a thick smear. 00:41:36.710 --> 00:41:41.182 But you're better able to determine whether it's falciparum 00:41:41.448 --> 00:41:44.969 or vivax or evali or malaria on a thin smear. 00:41:45.236 --> 00:41:48.355 So that's that's a helpful way to look at this. 00:41:48.355 --> 00:41:53.244 Also, one of the most sensitive ways to make a diagnosis is with PCR testing. 00:41:53.544 --> 00:41:55.679 That's a very expensive way. 00:41:55.679 --> 00:41:58.465 But it's very sensitive 00:41:58.465 --> 00:42:01.435 and it's very specific. 00:42:01.435 --> 00:42:03.921 And it will pick up mixed infections. 00:42:03.921 --> 00:42:05.839 So an advantage to it. 00:42:05.839 --> 00:42:08.792 But it's so expensive and so high tech. 00:42:08.792 --> 00:42:13.430 It's not used except usually in in a research labs 00:42:13.797 --> 00:42:16.700 recently there's a new rapid test. 00:42:16.700 --> 00:42:18.569 It's almost like a pregnancy test. 00:42:18.569 --> 00:42:21.589 You put a drop of blood on a piece of filter paper. 00:42:21.722 --> 00:42:23.941 You put two drops of developer on it. 00:42:23.941 --> 00:42:26.393 It migrates up the up the, 00:42:27.978 --> 00:42:29.096 filter paper. 00:42:29.096 --> 00:42:33.751 And if it's falciparum malaria, you'll have two, two stripes. 00:42:33.751 --> 00:42:36.737 And if it's all other malaria, you'll have one stripe. 00:42:37.171 --> 00:42:41.508 And you can tell within about ten minutes, how to do this. 00:42:41.508 --> 00:42:45.145 This then, is becoming the method of choice, 00:42:45.379 --> 00:42:48.382 because then you don't even need a microscope. 00:42:48.532 --> 00:42:53.187 All you need is someone a drop of blood in someone to to to can read it. 00:42:53.571 --> 00:42:59.193 And it looks at two different things the an antigen and a histidine 00:42:59.193 --> 00:43:02.663 rich protein antigen and a LDH antigen. 00:43:03.347 --> 00:43:06.083 And this is sensitive. It's simple. 00:43:06.083 --> 00:43:08.002 It's not very expensive. 00:43:08.002 --> 00:43:10.788 And many countries now are using this. 00:43:10.788 --> 00:43:13.941 And we use that here in our laboratory. 00:43:13.941 --> 00:43:18.479 When I see someone I order this test because I can get that back, 00:43:18.629 --> 00:43:21.865 usually within an hour or 2 to 2 hours. 00:43:24.118 --> 00:43:27.054 So prevention vaccination. 00:43:27.054 --> 00:43:30.507 We have worked on a vaccine for malaria for years and years, 00:43:30.858 --> 00:43:32.810 and nothing has ever worked. 00:43:32.810 --> 00:43:35.462 We have a vaccine now that's been tried out. 00:43:35.462 --> 00:43:40.651 And and we have friends in Ghana who are who are, researchers in this area. 00:43:40.968 --> 00:43:43.404 And it works a little bit. 00:43:43.404 --> 00:43:46.907 So maybe a 50% chance of working over 00:43:46.907 --> 00:43:51.328 six months, not as not a vaccine like we'd like to have. 00:43:51.328 --> 00:43:52.613 We'd like to have one that's 00:43:52.613 --> 00:43:55.616 absolutely preventive and give you a lifetime immunity. 00:43:55.833 --> 00:43:59.987 This is not that vaccine, but it's the best we've ever done. 00:44:00.421 --> 00:44:03.841 And we're hopeful that vaccination may be, 00:44:04.642 --> 00:44:08.178 may be a useful tool in eradicating this disease. 00:44:09.263 --> 00:44:10.547 So what do we do? 00:44:10.547 --> 00:44:15.235 We we we screen housing in in Ghana and the little villages 00:44:15.235 --> 00:44:18.956 that we showed you early almost impossible to put screens on. 00:44:19.323 --> 00:44:23.060 There are too many places in the house the mosquitoes can get in. 00:44:23.811 --> 00:44:28.532 So if you can't get screens on the windows then mosquito netting over the beds. 00:44:28.732 --> 00:44:32.302 And we have an advantage now in that there's an insecticide, 00:44:32.302 --> 00:44:37.224 we can spray these bed nets with that actually will kill mosquitoes. 00:44:38.092 --> 00:44:41.428 And so the, the bed nets are much more effective 00:44:41.729 --> 00:44:44.098 than when we used them in the past. 00:44:44.098 --> 00:44:46.967 So, bed nets are a huge, 00:44:46.967 --> 00:44:50.871 are a part of our own barium to treat, to get rid of this organism. 00:44:51.171 --> 00:44:55.826 We can also use clothing and treat it with the same thing. 00:44:55.893 --> 00:44:59.930 So when I go to to Ghana, I spray my clothing with a, 00:45:00.931 --> 00:45:02.966 a chemical called permethrin. 00:45:02.966 --> 00:45:04.952 And that helps protect me. 00:45:04.952 --> 00:45:09.857 We can use Deet on our skin to, repel mosquitoes. 00:45:10.641 --> 00:45:13.010 And so that's the way 00:45:13.010 --> 00:45:16.230 we try and decrease the risk to us 00:45:16.580 --> 00:45:19.583 as we go into mosquito areas. 00:45:19.733 --> 00:45:22.069 We can also take medication. 00:45:22.069 --> 00:45:26.090 We don't want very few places in the world now where chloroquine works, 00:45:26.423 --> 00:45:29.393 but there are at least three other good medications 00:45:29.393 --> 00:45:33.480 that we can take to try and prevent almost all of these. 00:45:33.714 --> 00:45:37.918 If you remember back, with regards to falciparum malaria, 00:45:38.252 --> 00:45:41.238 all of these are focused on falciparum malaria. 00:45:41.338 --> 00:45:45.559 They don't prevent vivax and valley malaria very well 00:45:45.776 --> 00:45:49.079 because they don't kill the organism in the liver. 00:45:49.913 --> 00:45:52.916 Only once it gets into the red blood cells. 00:45:53.901 --> 00:45:57.588 Treatment wise, there's still some places we can use chloroquine, 00:45:57.838 --> 00:46:02.359 but the biggest advance in treatment is a new medicine called our innate 00:46:02.359 --> 00:46:05.362 luma phantom. It's two medications. 00:46:05.696 --> 00:46:10.200 Our test and aid is from an herbal, medication used in China 00:46:10.584 --> 00:46:13.737 that has the ability to kill malaria 00:46:14.004 --> 00:46:17.391 better and faster than anything we've ever had. 00:46:17.724 --> 00:46:19.009 It is the, 00:46:20.727 --> 00:46:23.147 medication that that actually 00:46:23.147 --> 00:46:26.934 can kill some of these marginalized red cells or, 00:46:27.167 --> 00:46:31.321 infected red cells that are in our that in our, circulation. 00:46:31.588 --> 00:46:34.041 They do that better than any of the others. 00:46:34.041 --> 00:46:36.977 So the treatment of choice worldwide now 00:46:36.977 --> 00:46:39.797 is our test and innate Lumiere Phantom. 00:46:39.797 --> 00:46:43.016 And, it's available also here in Salt Lake City. 00:46:43.817 --> 00:46:47.521 But there are some others, total protocol proven on mefloquine. 00:46:47.754 --> 00:46:51.408 If these people are so sick or or unconscious, 00:46:51.558 --> 00:46:56.446 we can use our six and eight IV, or we still use quinine 00:46:56.697 --> 00:46:59.867 or nowadays we use another thing called clementine. 00:47:00.617 --> 00:47:03.003 So, if they're unconscious 00:47:03.003 --> 00:47:06.657 and we need to use IV medication, there's some IV medication. 00:47:06.924 --> 00:47:10.043 And then you remember the hypnosis, the lights in the liver 00:47:10.260 --> 00:47:12.513 that may hide out for months or years. 00:47:12.513 --> 00:47:16.283 The only medicine that kills them effectively is primary one. 00:47:16.667 --> 00:47:21.421 And so we use that when we find that, those those problems. 00:47:22.489 --> 00:47:23.123 This is just 00:47:23.123 --> 00:47:26.126 a summary of that, with regards to, 00:47:26.877 --> 00:47:29.630 the agent, whether it is used for prevention, 00:47:29.630 --> 00:47:33.300 whether it's for treatment and whether it can be used in pregnancy. 00:47:33.617 --> 00:47:34.701 Oops. 00:47:34.701 --> 00:47:38.272 And then finally, if we just look at the medications, 00:47:39.239 --> 00:47:41.842 this differentiates them just a little bit. 00:47:41.842 --> 00:47:44.161 Talks a little bit about their toxicity. 00:47:44.161 --> 00:47:47.664 Again the world health drug of choice is our 00:47:47.664 --> 00:47:50.667 is the artist honored with the Lumiere Phantom. 00:47:51.535 --> 00:47:54.071 And that then 00:47:54.071 --> 00:47:56.640 has a better chance of success 00:47:56.640 --> 00:47:59.643 than any of the other medications. 00:47:59.793 --> 00:48:01.979 All right, I think that's it. 00:48:01.979 --> 00:48:02.880 Any questions?