WEBVTT 00:00:07.974 --> 00:00:08.391 Well, it's my 00:00:08.391 --> 00:00:11.511 pleasure today to introduce Doctor Maggie Hopkins. 00:00:12.262 --> 00:00:16.766 Doctor Hopkins did an undergraduate degree in chemistry. 00:00:16.800 --> 00:00:19.703 Yeah, at Loyola in New Orleans. 00:00:19.703 --> 00:00:21.988 And then she, 00:00:21.988 --> 00:00:26.126 went to medical school, earning both her MD and her MBA 00:00:26.126 --> 00:00:29.579 at the same time, at Tulane, also in New Orleans. 00:00:30.080 --> 00:00:33.433 But she hails from Portland, so she doesn't have a nice southern drawl, 00:00:33.450 --> 00:00:36.453 so. Oh, well, we'll forgive her that, 00:00:36.753 --> 00:00:39.739 her she, is a straight, 00:00:39.773 --> 00:00:43.009 clinical pathology resident in her first year. 00:00:43.910 --> 00:00:46.613 Most of our residents do this rotation 00:00:46.613 --> 00:00:49.616 in their second year, but that's because they're APC. 00:00:49.649 --> 00:00:52.702 When you're straight CP, you end up taking this rotation in your first year. 00:00:53.403 --> 00:00:56.539 So she's a first year resident and, her talk 00:00:56.539 --> 00:01:01.561 today, is on syphilis, which, should be quite informative. 00:01:01.828 --> 00:01:04.380 With that, I'll turn it over to Doctor Hopkins. 00:01:04.380 --> 00:01:06.116 Thank you. Doctor Ashland. 00:01:06.116 --> 00:01:09.769 And, I do come from New Orleans, and I have to say 00:01:09.769 --> 00:01:12.839 that people from New Orleans don't really have a southern accent. 00:01:12.872 --> 00:01:14.958 They sound kind of like they're from Brooklyn. 00:01:14.958 --> 00:01:18.261 So if you hear me say some words a little odd, it could be that, 00:01:20.246 --> 00:01:23.183 So today I want to talk to you about syphilis. 00:01:23.183 --> 00:01:26.753 One of my favorite topics that it's just so interesting to me. 00:01:26.753 --> 00:01:29.072 And there's so much to cover with this topic. 00:01:29.072 --> 00:01:31.374 You can go into so much detail, such breadth 00:01:31.374 --> 00:01:34.377 and such depth that I was really only able to scratch the surface. 00:01:34.794 --> 00:01:37.797 So I'll get started now. 00:01:38.098 --> 00:01:41.101 First of all, I don't have anything to disclose. 00:01:42.952 --> 00:01:43.937 And I there's a few things 00:01:43.937 --> 00:01:46.940 I'd like you to take away from this talk, 00:01:46.973 --> 00:01:50.477 including being able to describe the four stages of syphilis 00:01:51.077 --> 00:01:55.849 and be able to list at least one defining characteristic of each of those stages 00:01:56.099 --> 00:01:59.969 with the compounds discovered and used in the treatment of of of syphilis 00:02:00.203 --> 00:02:03.323 throughout history, in order of efficacy, which will be pretty clear, 00:02:03.323 --> 00:02:07.911 I'm presenting them in order, and then critically evaluate the ethics of research 00:02:07.911 --> 00:02:13.500 conducted on patients with syphilis in Tuskegee, Alabama, and in Guatemala. 00:02:14.551 --> 00:02:18.271 And then when I get into the testing methods 00:02:18.271 --> 00:02:21.925 and the algorithms used for screening, I want you to be able to compare the pros 00:02:21.925 --> 00:02:24.928 and cons of, reverse algorithm 00:02:25.011 --> 00:02:28.681 and the traditional algorithm for screening and diagnosis of syphilis. 00:02:30.383 --> 00:02:31.351 Here's my outline. 00:02:31.351 --> 00:02:34.938 I'm going to start with a case of a little girl I actually treated 00:02:35.238 --> 00:02:37.073 at University Hospital in New Orleans. 00:02:37.073 --> 00:02:41.394 So this is a rare treat that, an actual, patient care. 00:02:41.461 --> 00:02:44.781 I'll be able to present some aspects of her patient care and learn from that. 00:02:45.431 --> 00:02:49.669 Then I'll get into the bug, syphilis and a description of it in all its gory 00:02:49.669 --> 00:02:52.672 detail, the stages of syphilis, how it's transmitted. 00:02:53.122 --> 00:02:57.093 And then we get the fun part, in my opinion, is the history of syphilis 00:02:57.260 --> 00:03:00.446 has such a rich history since it was first recognized in Europe. 00:03:01.014 --> 00:03:04.517 And then we'll get into, the treatment and how that's evolved over time, 00:03:04.517 --> 00:03:07.921 including Mercury Solverson and the invention of penicillin 00:03:08.838 --> 00:03:11.991 and and then a dark chapter in history, 00:03:12.625 --> 00:03:17.580 is going to be covering those two trials in, Tuskegee, Alabama, and Guatemala. 00:03:17.964 --> 00:03:20.900 And then I'll go over the current diagnostic algorithms and the tests 00:03:20.900 --> 00:03:24.470 that we use for syphilis, some of those that we do here at AARP. 00:03:25.939 --> 00:03:28.892 So here's the case or university, 00:03:28.892 --> 00:03:32.695 there was this 19 year old girl, she was brought into the emergency department, 00:03:32.912 --> 00:03:33.830 by ambulance. 00:03:33.830 --> 00:03:37.133 She'd been found unresponsive by her mom, passed out on the couch. 00:03:37.734 --> 00:03:41.571 And, the only part of her history we really had was, six months ago. 00:03:41.571 --> 00:03:44.390 She'd had an episode of autoimmune hemolytic anemia. 00:03:44.390 --> 00:03:47.627 She's very anemic, and she required, treatment with a blood transfusion. 00:03:47.627 --> 00:03:50.430 At that time. 00:03:50.430 --> 00:03:51.748 On physical exam. 00:03:51.748 --> 00:03:54.417 Here's her vitals. 00:03:54.417 --> 00:03:56.669 She is extremely to keep. 00:03:56.669 --> 00:03:58.888 Tachycardic. Her heart rate is really fast. 00:03:58.888 --> 00:04:02.725 123 the upper limit of normal is 100. 00:04:03.443 --> 00:04:04.277 She's to keep neck. 00:04:04.277 --> 00:04:06.479 That means she's breathing really fast. 00:04:06.479 --> 00:04:08.147 32 breaths per minute. Watch. 00:04:08.147 --> 00:04:10.700 Your me are only breathing about 12 or 18. 00:04:10.700 --> 00:04:11.868 Breath per minute. 00:04:11.868 --> 00:04:14.454 Her temperature is low 00:04:14.454 --> 00:04:15.805 on pulse oximetry. 00:04:15.805 --> 00:04:18.808 This is measuring the saturation of oxygen in her blood. 00:04:18.925 --> 00:04:21.744 It's 100% on room air. That's a little unusual. 00:04:21.744 --> 00:04:23.963 Usually we're only about 99 and a normal person. 00:04:23.963 --> 00:04:25.048 But she's breathing so fast. 00:04:25.048 --> 00:04:25.531 It's her. 00:04:25.531 --> 00:04:29.719 O2 is that high, and she had a rash on her palms and soles. 00:04:30.153 --> 00:04:31.821 But that wasn't her primary complaint. 00:04:31.821 --> 00:04:35.508 She's actually about to die, so we took care of treating her first 00:04:35.508 --> 00:04:38.161 and sort of ignored the rash at that point. 00:04:38.161 --> 00:04:41.481 So here's, we did a lot of labs, but this is the most interesting one. 00:04:41.481 --> 00:04:45.418 This is an arterial blood gas, and I'll take a little time to explain it. 00:04:45.418 --> 00:04:49.222 And you can learn how to work up, an acidosis and alkalosis, 00:04:49.222 --> 00:04:52.225 figure out if it's respiratory or metabolic. 00:04:52.225 --> 00:04:54.027 And in this case, her pH. 00:04:54.027 --> 00:04:56.663 Her blood is 6.92. 00:04:56.663 --> 00:05:00.900 A normal blood is 7.356 to 7 point 4 or 5. 00:05:01.134 --> 00:05:02.702 So she's acidic. 00:05:02.702 --> 00:05:03.469 This is really bad. 00:05:03.469 --> 00:05:06.439 She could die from very low, very low blood pH. 00:05:08.157 --> 00:05:10.226 To figure out if it's, 00:05:10.226 --> 00:05:13.713 a respiratory cause you look to the CO2, 00:05:13.980 --> 00:05:17.183 if the CO2 is low, like she's been 00:05:17.183 --> 00:05:20.870 hyperventilating, you'd expect this to have a particular effect on her blood. 00:05:20.870 --> 00:05:21.988 Does anyone know what that is? 00:05:21.988 --> 00:05:24.991 If someone is hyperventilating, what happens to their blood? H. 00:05:27.243 --> 00:05:28.911 They get an alkalosis. 00:05:28.911 --> 00:05:29.696 And that's actually what? 00:05:29.696 --> 00:05:31.698 She's a respiratory alkalosis. 00:05:31.698 --> 00:05:33.900 Her CO2 is nine. 00:05:33.900 --> 00:05:37.587 That's how the body compensates for being acidic. 00:05:38.037 --> 00:05:41.574 Blowing off CO2 is going to try to raise that pH. 00:05:41.607 --> 00:05:46.045 A normal CO2 is between 35 and 45mm of mercury and hers is only nine. 00:05:46.646 --> 00:05:50.149 But when we look at her bicarb, the bicarb is the 00:05:50.149 --> 00:05:53.553 the main buffer in the blood for hydrogen ions, 00:05:54.504 --> 00:05:59.359 and a normal bicarb in the blood is 22 to 26 and hers is a two. 00:05:59.909 --> 00:06:01.828 So this is telling you whether, 00:06:02.995 --> 00:06:03.413 there is 00:06:03.413 --> 00:06:07.166 a metabolic cause, whether it's a metabolic acidosis or alkalosis. 00:06:07.166 --> 00:06:11.337 And she has a metabolic acidosis because the bicarb is so low. 00:06:12.572 --> 00:06:17.994 And since her blood pH is 6.92, that means that this is the primary thing 00:06:17.994 --> 00:06:20.997 that's going on here is this metabolic acidosis. 00:06:21.230 --> 00:06:24.500 You always follow the primary following the lead pH. 00:06:25.818 --> 00:06:29.639 She also has a really high blood glucose level 1500. 00:06:29.639 --> 00:06:31.441 This is outrageously high. 00:06:31.441 --> 00:06:34.127 And her urine is positive for ketones. 00:06:34.127 --> 00:06:37.163 So this is a pretty obvious diagnosis. 00:06:37.163 --> 00:06:39.832 But does anybody here know what that is. 00:06:39.832 --> 00:06:42.835 This is the only chemistry for the medical. 00:06:47.156 --> 00:06:50.159 Nobody. 00:06:52.462 --> 00:06:55.465 Yes, she is diabetic ketoacidosis. 00:06:55.798 --> 00:06:57.200 What does this have to do with syphilis? 00:06:57.200 --> 00:06:58.801 I'm not sure, but this is the case. 00:06:58.801 --> 00:07:01.521 I have. 00:07:01.521 --> 00:07:03.990 So what's the treatment for diabetic ketoacidosis? 00:07:05.007 --> 00:07:06.242 I.V. fluid and insulin. 00:07:06.242 --> 00:07:08.060 So that's what we gave her. 00:07:08.060 --> 00:07:10.580 And so we we gave her hydration and insulin therapy, 00:07:10.580 --> 00:07:12.198 and she starts to get better the next day. 00:07:12.198 --> 00:07:15.051 She's actually able to converse and tells us that she's feeling better. 00:07:15.051 --> 00:07:18.438 And, the next morning I'm doing the physical exam. 00:07:18.438 --> 00:07:20.840 So when you're on the internal medicine rotation every morning, 00:07:20.840 --> 00:07:23.009 you go to see your patients in in their room 00:07:23.009 --> 00:07:24.444 and you do a physical exam on them. 00:07:24.444 --> 00:07:27.363 And I'm noticing this, this rash on her palm and soles. 00:07:27.363 --> 00:07:31.100 And maybe we should do something about this now, that she's better. 00:07:31.100 --> 00:07:33.052 We can address her a secondary complaint here. 00:07:33.052 --> 00:07:35.571 I'm wondering, does it have anything to do with her condition? Not. 00:07:35.571 --> 00:07:36.322 Probably not. 00:07:36.322 --> 00:07:38.191 I'm not aware of of, 00:07:38.191 --> 00:07:41.627 diabetic ketoacidosis or even diabetes causing a rash like that. 00:07:42.278 --> 00:07:43.262 This is what it looked like. 00:07:44.580 --> 00:07:46.399 So there are these target 00:07:46.399 --> 00:07:50.786 shaped lesions on her palms and also on the soles of her feet. 00:07:52.405 --> 00:07:54.207 And, there's 00:07:54.207 --> 00:07:57.927 only so many things that can cause a rash like that on the palms and the soles. 00:07:57.927 --> 00:07:59.996 This is a list of a few of those things. 00:07:59.996 --> 00:08:01.981 Some of them are infectious diseases, 00:08:01.981 --> 00:08:05.485 and some of them we were actually able to treat for at our hospital lab. 00:08:05.701 --> 00:08:09.505 I didn't have access to a fancy lab like area up at that time at University 00:08:09.505 --> 00:08:12.992 Hospital in New Orleans, but secondary syphilis is on this list. 00:08:13.493 --> 00:08:15.077 So we started an infectious disease 00:08:15.077 --> 00:08:16.979 workup, starting with the most obvious things. 00:08:16.979 --> 00:08:18.231 First, 00:08:18.231 --> 00:08:20.783 everyone who comes into the emergency department should get an HIV test. 00:08:20.783 --> 00:08:23.269 So that's what we did for her. In this case, it was negative. 00:08:23.269 --> 00:08:26.606 It's really important to rule out HIV in any patient, 00:08:26.606 --> 00:08:28.891 especially if you're suspecting something infectious. 00:08:28.891 --> 00:08:33.829 Because, in your typical patient, you, you follow, Occam's razor 00:08:33.829 --> 00:08:37.733 that the simplest explanation is probably the best and the true 00:08:37.733 --> 00:08:39.302 one that it could be causing. 00:08:39.302 --> 00:08:41.420 There's one one cause for all the patient's symptoms. 00:08:42.572 --> 00:08:44.490 This patient's complicated enough. 00:08:44.490 --> 00:08:46.559 She's probably got two things going on already. 00:08:46.559 --> 00:08:49.161 But if it's HIV, Occam's razor goes out the window, 00:08:49.161 --> 00:08:52.081 and the patient could have any number of infectious diseases. 00:08:52.081 --> 00:08:52.882 And many of them 00:08:52.882 --> 00:08:55.885 could be things that your average patient would not be susceptible to. 00:08:56.002 --> 00:08:58.170 So it's really great that she's negative for HIV. 00:08:58.170 --> 00:08:59.455 But what does she have? 00:08:59.455 --> 00:09:01.140 So we did a screening test for syphilis. 00:09:01.140 --> 00:09:04.143 This is the vDSL. And that was positive. 00:09:04.143 --> 00:09:06.445 We did the confirmatory test for FTA. Yes. 00:09:06.445 --> 00:09:08.064 Also positive. 00:09:08.064 --> 00:09:11.784 I'm going to get into what those letters mean in the near the end of the talk, 00:09:11.784 --> 00:09:15.271 when I discuss the treatment algorithms and the, the tests. 00:09:15.655 --> 00:09:17.573 So what's her diagnosis? 00:09:17.573 --> 00:09:19.375 Well, she's got syphilis. 00:09:19.375 --> 00:09:22.528 So what is this? What is the first? 00:09:22.562 --> 00:09:25.531 It's it's caused by a bug called chapel Anima pallidum. 00:09:27.116 --> 00:09:27.984 Now, chapel 00:09:27.984 --> 00:09:31.137 name of pallidum is a really neat looking bacteria. 00:09:31.137 --> 00:09:33.990 It's a spiral, which means it's spiral shaped. 00:09:33.990 --> 00:09:35.791 And it's motile. It can move. 00:09:35.791 --> 00:09:40.680 It actually moves in this corkscrew like manner to wind its way through mucus. 00:09:40.680 --> 00:09:45.234 That's where it loves to hide out is warm, moist places like mucous membranes. 00:09:46.669 --> 00:09:50.723 And that's how it's most commonly passed through sexual transmission. 00:09:51.440 --> 00:09:53.943 Sexual, sexual contact, 00:09:53.943 --> 00:09:57.797 or rarely, it can be passed from mucous membrane to mucous membrane. 00:09:58.080 --> 00:10:01.067 It can also pass from mom to baby, through the placenta 00:10:01.133 --> 00:10:03.619 or through blood products in the transfusion. 00:10:03.619 --> 00:10:06.422 And it is this potentially where our patient got it. 00:10:06.422 --> 00:10:07.523 Although at 19 years old, 00:10:07.523 --> 00:10:10.526 she certainly could have been doing other things that put her at risk. 00:10:12.178 --> 00:10:14.747 People who are exposed for sexual contact, up 00:10:14.747 --> 00:10:18.985 30 to 60% of them, will become infected with primary syphilis. 00:10:20.453 --> 00:10:22.672 The incidence in 2011. 00:10:22.672 --> 00:10:24.357 These figures are from the CDC. 00:10:24.357 --> 00:10:27.593 There were about 46,000 new cases diagnosed, 00:10:29.128 --> 00:10:32.331 and only a third of these were primary or secondary. 00:10:32.732 --> 00:10:33.649 This is important. 00:10:33.649 --> 00:10:36.619 The primary secondary is referring to the stages of syphilis. 00:10:36.619 --> 00:10:37.787 These are the first two stages. 00:10:37.787 --> 00:10:39.805 I'll get into the details in the second. 00:10:39.805 --> 00:10:42.692 But this is the most treatable kind of syphilis. 00:10:42.692 --> 00:10:45.478 And the the patient will pass through these first two stages within the 00:10:45.478 --> 00:10:46.579 first year. 00:10:46.579 --> 00:10:49.582 And if you don't catch it, then it's a lot harder to treat. 00:10:49.849 --> 00:10:53.102 There were also 360 cases of congenital syphilis. 00:10:54.353 --> 00:10:56.305 The CDC estimates that there's 00:10:56.305 --> 00:10:59.725 about 55,000 new infections annually. 00:10:59.725 --> 00:11:05.514 So if we're only catching about, it was 15,000 primary and secondary cases. 00:11:05.781 --> 00:11:07.166 Of all the new infections, 00:11:07.166 --> 00:11:10.970 about 40,000 of them are going to go on potentially to the tertiary stage, 00:11:11.187 --> 00:11:13.706 or they'll be latent for a while passing that infection on. 00:11:13.706 --> 00:11:15.991 So we're not doing a very good job of catching this early. 00:11:17.276 --> 00:11:20.329 Patients who are particularly at risk of developing syphilis 00:11:20.629 --> 00:11:23.666 are homosexual men who have sex with men. 00:11:24.150 --> 00:11:25.217 High rate of transmission. 00:11:25.217 --> 00:11:27.086 There, and also HIV. 00:11:27.086 --> 00:11:30.089 HIV makes the person more susceptible to any infectious disease 00:11:30.089 --> 00:11:33.509 and also having syphilis, especially the primary, a canker 00:11:33.509 --> 00:11:37.563 sore on the genitals increases the risk of transmission of HIV as well. 00:11:38.698 --> 00:11:42.568 And of course, babies of infected moms have the risk of being transmitted 00:11:42.568 --> 00:11:45.838 through the placenta if they are not, in fact, aborted by the disease. 00:11:46.338 --> 00:11:49.308 So syphilis progresses through four stages. 00:11:49.308 --> 00:11:53.329 Like I said, the first, the primary stage and then secondary. 00:11:53.763 --> 00:11:55.981 The third stage is actually called the latent stage 00:11:55.981 --> 00:11:58.250 because there may not be any symptoms during this time. 00:11:58.250 --> 00:12:01.971 And then, maybe ten years later, the patient may progress 00:12:01.971 --> 00:12:06.709 to the tertiary final stage, which is the most dreaded congenital. 00:12:06.709 --> 00:12:09.712 Syphilis is another syndrome that I'll go over 00:12:10.346 --> 00:12:13.466 primary syphilis after the patient is exposed. 00:12:14.366 --> 00:12:18.571 About a maybe a month later, the develop this canker saw an ulcer. 00:12:18.571 --> 00:12:21.991 And it always occurs on the part of the body that was first infected. 00:12:22.458 --> 00:12:25.227 And, this is usually the genitalia. 00:12:25.227 --> 00:12:26.512 But since this is a lunch talk, 00:12:26.512 --> 00:12:28.848 I didn't want to put any pictures of genitalia here. 00:12:28.848 --> 00:12:31.817 So rest assured, there's no nothing like that. 00:12:31.817 --> 00:12:33.869 But this is plenty aggressive enough. 00:12:33.869 --> 00:12:36.272 This man was infected on his finger. 00:12:36.272 --> 00:12:40.676 He may have had a, a cut there the bug got into to make this, 00:12:42.361 --> 00:12:43.162 So it develops 00:12:43.162 --> 00:12:46.282 this canker, and that can actually go away after about a month. 00:12:46.282 --> 00:12:47.967 And the patient might think that everything's fine 00:12:47.967 --> 00:12:49.018 and there's nothing going on, 00:12:49.018 --> 00:12:52.021 but the bugs actually gone underground, and it's going to pop back up 00:12:52.221 --> 00:12:56.041 a secondary syphilis and this happens, a couple months later. 00:12:56.041 --> 00:12:57.393 It can last a few months. 00:12:57.393 --> 00:12:59.695 Symptoms come and go throughout this time. 00:12:59.695 --> 00:13:04.550 They may feel pretty bad malaise, have a headache, swollen lymph nodes, 00:13:05.568 --> 00:13:07.369 pain all over their body. 00:13:07.369 --> 00:13:08.420 They may lose weight. 00:13:08.420 --> 00:13:10.823 They may lose their hair or the skin rash. 00:13:10.823 --> 00:13:15.294 This is really the defining characteristic of secondary syphilis is a rash 00:13:15.294 --> 00:13:19.381 that can cover the whole body, but particularly on the palms and the soles. 00:13:19.381 --> 00:13:21.534 And this is what our patient was exhibiting. 00:13:21.534 --> 00:13:25.704 This is like round target like lesions on the palms in the soles. 00:13:27.439 --> 00:13:28.524 Latent syphilis. 00:13:28.524 --> 00:13:29.875 After six months or so, 00:13:29.875 --> 00:13:33.145 the symptoms can go away and the patient becomes latent. 00:13:33.596 --> 00:13:37.082 And, this can actually continue indefinitely because 50 00:13:37.082 --> 00:13:40.653 to 70% of patients don't progress on to the tertiary stage. 00:13:41.637 --> 00:13:45.658 But for those that do, this is the most dreaded stage of syphilis. 00:13:46.008 --> 00:13:49.011 It happens about ten years later. 00:13:49.011 --> 00:13:51.797 They develop lesions anywhere in their body, 00:13:51.797 --> 00:13:55.167 on the skin and the bones and even in their organs. 00:13:55.501 --> 00:13:57.653 This here is a gamma. 00:13:57.653 --> 00:14:00.272 But these lesions are called because they're gummy looking, 00:14:00.272 --> 00:14:01.891 and they can go all the way 00:14:01.891 --> 00:14:04.877 through the bone, destroy the skeletons during the skin. 00:14:05.361 --> 00:14:08.364 This is, a man's forehead. 00:14:08.397 --> 00:14:11.400 These are the eyebrows. They're. 00:14:11.600 --> 00:14:14.336 There are, two more syndromes associated with tertiary. 00:14:14.336 --> 00:14:16.038 So first, I'll get into a little more detail 00:14:16.038 --> 00:14:18.841 on cardiovascular syphilis and neuro syphilis. 00:14:20.342 --> 00:14:22.528 Cardiovascular syphilis? 00:14:22.528 --> 00:14:26.398 The bug has a particular interest in getting inside your arteries. 00:14:26.432 --> 00:14:30.953 The aorta in particular around the aortic arch and the aortic valve. 00:14:31.103 --> 00:14:34.823 And it destroys the elastic fibers inside the aorta. 00:14:35.341 --> 00:14:37.877 It can cause huge aneurysms of the aorta. 00:14:37.877 --> 00:14:42.414 Stretch out the aortic valve so big that the heart becomes hugely distended. 00:14:42.498 --> 00:14:44.633 And this was called core bovine. 00:14:44.633 --> 00:14:48.687 And this is actually a contemporary case of a man who developed this. 00:14:48.921 --> 00:14:49.555 It's so bad. 00:14:49.555 --> 00:14:52.524 The aneurysm of his aorta is so big. 00:14:52.524 --> 00:14:55.160 And there was bony destruction of his sternum. 00:14:55.160 --> 00:14:58.163 It's pushing and pulsating out through his chest. 00:14:59.632 --> 00:15:01.317 Neural syphilis. 00:15:01.317 --> 00:15:05.154 This used to be a really common cause of psychiatric illness. 00:15:05.154 --> 00:15:06.772 And put a lot of people in. 00:15:06.772 --> 00:15:11.093 In asylums, and it used to be called the general paresis of the insane, 00:15:11.093 --> 00:15:14.930 along with personality changes and maybe even frank psychosis. 00:15:15.147 --> 00:15:17.583 They would have a partial paralysis of their limbs. 00:15:17.583 --> 00:15:18.751 That's what paresis means. 00:15:20.903 --> 00:15:24.173 It also causes something called Argyle Robinson's pupil. 00:15:24.290 --> 00:15:26.759 We learned about this in medical school as prostitutes. 00:15:26.759 --> 00:15:29.762 Pupil accommodates but doesn't react. 00:15:29.912 --> 00:15:32.298 That's referring to the accommodation reflex. 00:15:32.298 --> 00:15:37.886 When you hold an object close to a patient's face, the pupils will constrict. 00:15:38.270 --> 00:15:41.573 When you shine a light in someone's eyes, the pupils are supposed to constrict. 00:15:41.957 --> 00:15:45.828 But in Argyle Robinson's pupil, the pupils do not constrict to light. 00:15:45.828 --> 00:15:47.579 Shine a light on them. They don't change. 00:15:47.579 --> 00:15:51.150 But if you put the object close to their face, the pupils do constrict. 00:15:51.500 --> 00:15:55.437 That's because syphilis likes to destroy the brain 00:15:55.437 --> 00:15:59.491 from the back forward, and the nuclei that control the, 00:15:59.792 --> 00:16:03.262 pupillary constriction response are further back in the brain. 00:16:03.562 --> 00:16:07.800 And the one that controls accommodation is more towards the middle and protected. 00:16:09.418 --> 00:16:11.637 Another example of how it destroys 00:16:11.637 --> 00:16:14.757 the back of the brain in the spinal cord is dorsal. 00:16:16.258 --> 00:16:18.177 This can in this condition, 00:16:18.177 --> 00:16:21.230 it destroys the posterior columns of the spinal cord. 00:16:21.497 --> 00:16:24.800 This is a spinal cord with a myelin stain. 00:16:25.184 --> 00:16:26.869 It's standing myelin dark. 00:16:26.869 --> 00:16:31.790 This is a normal spinal cord and it's a little darker. 00:16:31.790 --> 00:16:34.526 The the stains are just slightly different between these. 00:16:34.526 --> 00:16:37.279 But this is what it should look like with these nice big fat 00:16:37.279 --> 00:16:40.582 sort of triangle shape area here. 00:16:40.733 --> 00:16:42.651 The chrysalis in Cooney Odyssey. 00:16:42.651 --> 00:16:47.573 And these, tracts of neurons, they control pain and temperature, 00:16:47.823 --> 00:16:50.909 especially the lower limbs and, proprioception, 00:16:50.909 --> 00:16:53.929 which is the ability to tell where your feet are when you're walking. 00:16:54.263 --> 00:16:57.499 If you had your eyes closed, you can still tell where you're putting your feet. 00:16:57.866 --> 00:17:00.085 But these are destroyed. The turf. 00:17:00.085 --> 00:17:00.803 When you move pallidum, 00:17:00.803 --> 00:17:04.373 it gets in here and destroys just the posterior columns preferentially 00:17:04.556 --> 00:17:07.943 with demyelination and destruction of this area of the spinal cord. 00:17:08.210 --> 00:17:12.081 And it causes a particularly funny kind of walk where they will lift 00:17:12.081 --> 00:17:13.382 their feet up very high. 00:17:13.382 --> 00:17:14.700 They are not sure where they're placing them 00:17:14.700 --> 00:17:16.735 and sort of slapping the foot down on the ground. 00:17:18.620 --> 00:17:19.738 Congenital syphilis. 00:17:19.738 --> 00:17:21.023 This is the, 00:17:21.023 --> 00:17:24.810 condition that the baby can contract if they actually survive the pregnancy. 00:17:25.160 --> 00:17:28.247 There are some congenital deformities 00:17:28.247 --> 00:17:31.250 that develop as they get older, including, 00:17:32.634 --> 00:17:33.869 saber shins. 00:17:33.869 --> 00:17:35.971 The shin is shaped funny. 00:17:35.971 --> 00:17:37.172 Kind of like a saber. 00:17:37.172 --> 00:17:40.159 Hutchinson's teeth, they get sorry, 00:17:41.126 --> 00:17:44.780 these, notches in their teeth when the teeth come in. 00:17:45.481 --> 00:17:48.383 And saddle nose deformity. 00:17:48.383 --> 00:17:50.903 That's been the, the the bones of the face 00:17:50.903 --> 00:17:53.906 have just been destroyed here. 00:17:54.323 --> 00:17:55.290 So syphilis in 00:17:55.290 --> 00:17:58.427 its advanced stages can mimic just about any disease, 00:17:58.427 --> 00:18:01.463 any immune mediated process, inflammatory 00:18:01.463 --> 00:18:04.466 disease, infectious disease and some chronic illnesses, 00:18:04.466 --> 00:18:08.220 like cardiovascular disease causing an aortic aneurysm like we saw. 00:18:08.604 --> 00:18:12.291 So for this reason, it's been called the Great imitator by Sir William Osler. 00:18:12.508 --> 00:18:15.561 And he stated that the physician who knows syphilis knows medicine 00:18:15.561 --> 00:18:18.647 because there is just so much to know about what it can cause. 00:18:20.099 --> 00:18:21.717 Syphilis, since it 00:18:21.717 --> 00:18:26.338 was first recognized in Europe, has inspired literature, art and poetry. 00:18:26.455 --> 00:18:30.259 As you'll see from my favorite poem about syphilis, this Limerick here, 00:18:30.542 --> 00:18:33.779 which is, an anonymous poem from about 1920. 00:18:34.263 --> 00:18:37.733 And as I read it, try and recognize the different stages of syphilis 00:18:37.733 --> 00:18:40.102 that are described in here quite accurately. 00:18:40.102 --> 00:18:43.972 There was a young man from black Bay who thought syphilis just went away. 00:18:44.156 --> 00:18:47.993 He believed that a canker was only a canker that healed in a week and a day. 00:18:48.377 --> 00:18:52.998 But now he has acne vulgaris, or whatever they call it, in Paris, on his skin. 00:18:52.998 --> 00:18:54.833 It has spread from his feet to his head, 00:18:54.833 --> 00:18:57.169 and his friends wants to know where his hair is. 00:18:57.169 --> 00:18:58.937 There's more to his terrible plight. 00:18:58.937 --> 00:19:01.039 His pupils won't close in the light. 00:19:01.039 --> 00:19:03.509 His heart is cavorting, his wife is aborting, 00:19:03.509 --> 00:19:06.028 and he squints through his gun barrel site. 00:19:06.028 --> 00:19:10.015 Arthralgia cuts into his lumbar, his aorta, in need of a plumber. 00:19:10.349 --> 00:19:11.667 But now he has tabbies 00:19:11.667 --> 00:19:15.270 and sabers and babies, while of gammas, he has quite a number. 00:19:15.687 --> 00:19:19.525 He's been treated in every known way, but his spirit keeps grow day by day. 00:19:19.758 --> 00:19:20.492 He's developed 00:19:20.492 --> 00:19:24.630 paresis, has long talks with Jesus, and thinks he's the queen of the May. 00:19:28.433 --> 00:19:30.085 Now we're getting into the really fun part. 00:19:30.085 --> 00:19:33.088 Where'd syphilis come from? 00:19:33.438 --> 00:19:36.141 Syphilis first appeared in Europe in 1496, 00:19:36.141 --> 00:19:38.243 and when it did, it was a really terrible disease. 00:19:38.243 --> 00:19:42.147 These people would have severe ulcerations of their genitals to the point 00:19:42.147 --> 00:19:45.601 where it could be falling off and pustules all over their face and body. 00:19:45.601 --> 00:19:48.587 They had horrible smell, soft tissue eating away 00:19:48.587 --> 00:19:51.590 to the bone from those gums. 00:19:51.890 --> 00:19:55.377 There's two different theories about where syphilis came from. 00:19:55.561 --> 00:19:59.882 The first is that it, existed in the New World, and it was brought over, 00:20:00.649 --> 00:20:03.769 on Columbus's by Columbus's voyages. 00:20:03.769 --> 00:20:06.772 His men picked it up in Haiti or Hispaniola 00:20:06.772 --> 00:20:08.907 and brought it back over to Europe. 00:20:08.907 --> 00:20:11.910 The second is that it was already in Europe and just unrecognized. 00:20:11.960 --> 00:20:14.963 But, or it was confused with leprosy. 00:20:15.080 --> 00:20:17.666 I actually favor the first theory because I like to 00:20:17.666 --> 00:20:21.420 think about where syphilis likes to live in hot, humid places. 00:20:21.420 --> 00:20:25.641 And and over in the New World, in tropical climates, there is, diseases 00:20:25.641 --> 00:20:30.979 called pinta and yours, which are caused by a pallidum of a different subspecies. 00:20:31.530 --> 00:20:36.602 And this, this bug in those places that is just spread by skin contact. 00:20:36.902 --> 00:20:40.472 So you could imagine it getting picked up by the men who are new to this area, 00:20:40.472 --> 00:20:44.359 bringing it back over to Europe where it's cold, not nice and warm, 00:20:44.359 --> 00:20:47.629 and then the bug mutating into a form that likes to be passed through 00:20:47.629 --> 00:20:53.368 sexual transmission, kind of the way that, HPV and, genital warts has done. 00:20:54.453 --> 00:20:56.905 But wherever it came from, 00:20:56.905 --> 00:21:00.208 this is the defining moment that allowed it to be spread throughout Europe. 00:21:00.208 --> 00:21:04.313 Is that in 1494, a King, Charles the Eighth of France, attacked Naples 00:21:04.613 --> 00:21:08.550 with an army of mercenaries, including some men from Columbus's voyages. 00:21:09.167 --> 00:21:12.688 And whoever gave it to whom the men were having relations 00:21:12.688 --> 00:21:15.924 with the local prostitutes of Naples, and it was passed back and forth, 00:21:16.491 --> 00:21:21.530 and Naples being a major trade route, then subsequently anyone coming through 00:21:21.530 --> 00:21:24.916 Naples was bringing, and they visited those local prostitutes, 00:21:24.916 --> 00:21:27.919 and they're bringing home an extra souvenir back to their home country. 00:21:28.103 --> 00:21:31.740 And by the 15th century into the 15th century, 00:21:31.740 --> 00:21:34.259 there was a severe syphilis pandemic going on. 00:21:34.259 --> 00:21:37.913 It was so bad, like I described such a nasty new disease. 00:21:37.913 --> 00:21:39.564 Physicians didn't know what they were treating 00:21:39.564 --> 00:21:42.501 and they started to describe it as a new disease. 00:21:43.802 --> 00:21:44.987 It was called the Spanish 00:21:44.987 --> 00:21:48.890 disease, or the French pox or the Neapolitan evil. 00:21:48.890 --> 00:21:50.425 This kind of depending on where you were from 00:21:50.425 --> 00:21:53.161 and who your enemies were, you just blamed it on them. 00:21:53.161 --> 00:21:55.947 But it was often just called the great pox to distinguish 00:21:55.947 --> 00:21:59.368 it from smallpox, which was a different well known disease. 00:21:59.368 --> 00:22:02.371 But they both both caused the lesions all over the body. 00:22:03.472 --> 00:22:06.775 And in 1530 there was an Italian physician and poet. 00:22:07.075 --> 00:22:09.778 He wrote a poem called syphilis 00:22:09.778 --> 00:22:14.366 de CV, morbid galette, which means syphilis, the French disease, 00:22:14.366 --> 00:22:17.369 and in this poem he describes a beloved shepherd, 00:22:17.552 --> 00:22:21.323 and the shepherd's name was syphilis, which means lover of swine. 00:22:21.740 --> 00:22:24.593 And so what syphilis did was he angered the sun 00:22:24.593 --> 00:22:27.596 god of Haiti and was stricken with a terrible illness. 00:22:27.596 --> 00:22:32.000 And this poem had such great descriptions of the disease in all of its stages 00:22:32.184 --> 00:22:33.468 that everyone loved this poem. 00:22:33.468 --> 00:22:35.370 And they started to call that disease syphilis. 00:22:37.022 --> 00:22:37.439 So in 00:22:37.439 --> 00:22:40.559 this early syphilis pandemic, the disease made people extremely 00:22:40.559 --> 00:22:43.562 ill and people were actually dying even in the early stages. 00:22:43.945 --> 00:22:47.516 And by 1500, medical literature was filled with descriptions, 00:22:47.749 --> 00:22:48.917 new case descriptions. 00:22:48.917 --> 00:22:53.455 And this is only a few years after it, first landed or first recognized. 00:22:53.789 --> 00:22:57.059 By 1557, there were a leper colony set up 00:22:57.059 --> 00:23:00.062 throughout Europe, and but they weren't filled with people with leprosy. 00:23:00.062 --> 00:23:02.998 They filled with people with venereal disease. 00:23:02.998 --> 00:23:05.751 And by 1690, syphilitic patients, 00:23:05.751 --> 00:23:08.153 were treated in hospitals because the disease had toned down 00:23:08.153 --> 00:23:11.156 by this point, it wasn't quite as nasty a disease. 00:23:12.174 --> 00:23:15.293 The treatment at this time, a treatment choice was mercury. 00:23:15.827 --> 00:23:17.479 Actually. Mercury. 00:23:17.479 --> 00:23:21.299 So this brings us to the next section, which is covering the evolution of therapy 00:23:21.299 --> 00:23:24.152 and going into detail of the different drugs that have been used throughout time. 00:23:26.154 --> 00:23:29.391 So mercury has actually been used to treat skin infections 00:23:29.658 --> 00:23:34.162 since, 1025 is when it was first described in a Handbook of Medicine 00:23:34.379 --> 00:23:39.301 by a Persian physician, and it was used to treat any skin infection. 00:23:39.301 --> 00:23:41.103 So this was a natural choice. 00:23:41.103 --> 00:23:45.240 In 1496, some some Areva of Verona treated syphilis. 00:23:45.390 --> 00:23:48.243 That was the first one to use it to treat syphilis. 00:23:48.243 --> 00:23:51.179 There were multiple routes of administration of mercury, 00:23:51.179 --> 00:23:55.517 including oral taking it really in any form or topical, 00:23:55.517 --> 00:23:58.520 taking the elemental mercury and rubbing it on the ulcers 00:23:58.737 --> 00:24:01.740 or mixed in something as an ointment put on topically. 00:24:02.057 --> 00:24:05.060 Fumigation was a popular route of administration. 00:24:05.127 --> 00:24:08.130 In fact, they would put the patient into a box 00:24:08.430 --> 00:24:12.150 with their heads sticking out and fumigate their whole body with mercury fumes. 00:24:14.970 --> 00:24:15.737 And mercury 00:24:15.737 --> 00:24:18.740 remained popular for about three centuries. 00:24:18.924 --> 00:24:22.828 By the 1800s, it was used to treat any ulcer or pimple that you had, 00:24:23.395 --> 00:24:26.448 and patients were actually more injured from the treatment 00:24:26.448 --> 00:24:28.133 than they were from the disease. 00:24:28.133 --> 00:24:31.136 Some of the side effects of mercury were tooth loss, 00:24:31.369 --> 00:24:34.589 mouth ulcers, skin ulcers, neurological damage. 00:24:34.589 --> 00:24:36.107 They'd have personality changes. 00:24:36.107 --> 00:24:38.426 They could actually even just die from this. 00:24:38.426 --> 00:24:41.129 And it led to this saying that a knight in the arms of Venus 00:24:41.129 --> 00:24:44.132 leads to a lifetime on Mercury. 00:24:48.687 --> 00:24:51.356 Originally you would have to diagnose syphilis 00:24:51.356 --> 00:24:54.659 by either being a canker or by having the sores on the body. 00:24:54.659 --> 00:24:58.530 But there were a couple of discoveries in the early 1900s that enabled physicians 00:24:58.530 --> 00:25:01.533 to be able to diagnose the disease in asymptomatic stages. 00:25:01.650 --> 00:25:04.286 The first was that the the bug that caused it was discovered 00:25:04.286 --> 00:25:06.171 by some microbiologists, 00:25:06.171 --> 00:25:09.624 and they used a modified beam sustained to demonstrate the check. 00:25:09.624 --> 00:25:14.246 When you move pallidum organism in some syphilitic sores of tissue from a patient. 00:25:14.696 --> 00:25:17.899 And in 1906, some German researchers developed the Wasserman test 00:25:18.116 --> 00:25:21.686 using complement fixation to detect antibodies that were, 00:25:22.070 --> 00:25:25.073 probably not specific, but, were seen in patients with syphilis 00:25:25.524 --> 00:25:27.025 and testing people in Europe. 00:25:27.025 --> 00:25:31.229 They found the prevalence was extremely high, up to 15% in in Paris. 00:25:31.846 --> 00:25:33.481 But now that the disease could be caught 00:25:33.481 --> 00:25:36.468 in the asymptomatic stages, it's ripe for a treatment. 00:25:36.535 --> 00:25:39.538 But all we need is a treatment that's actually effective. 00:25:39.838 --> 00:25:42.023 So this brings us to Paul Ehrlich. 00:25:42.023 --> 00:25:46.378 In 1909, he was working in a new field of chemotherapy, 00:25:46.578 --> 00:25:50.181 and the field of chemotherapy was to take 00:25:50.181 --> 00:25:53.668 a, chemical and treat microbial illness. 00:25:53.852 --> 00:25:57.539 And in particular, Paul Ehrlich had this idea, this vision 00:25:57.839 --> 00:26:00.859 that he described as a silver bullet, which would be a compound 00:26:00.859 --> 00:26:03.895 that could kill the bug and not harm the patient at all. 00:26:04.195 --> 00:26:05.430 The opposite of Mercury. 00:26:05.430 --> 00:26:08.366 I mean, if it's going to kill the patient, it's not a very effective treatment. 00:26:09.601 --> 00:26:11.836 So he started, 00:26:11.836 --> 00:26:15.173 testing in earnest on about 900 different compounds. 00:26:15.390 --> 00:26:18.393 He went through them one by one, testing them on mice. 00:26:19.344 --> 00:26:23.548 And his assistant at one point decided to go back to number 606. 00:26:24.082 --> 00:26:27.802 And he tested this one on mice and guinea pigs and rabbits with syphilis. 00:26:28.136 --> 00:26:29.337 And it seemed to work pretty well. 00:26:29.337 --> 00:26:32.907 They actually got complete cures within three weeks and no dead animals at all. 00:26:33.291 --> 00:26:36.595 So they, they released this drug in 1910 00:26:36.595 --> 00:26:42.000 and it was called solverson or arsenic safe because in in the drug 00:26:42.150 --> 00:26:45.537 it's a dimer of solverson are arsenic molecules. 00:26:47.489 --> 00:26:48.923 So solverson was the world's 00:26:48.923 --> 00:26:52.761 first chemotherapeutic agent for treating a microbial illness. 00:26:52.761 --> 00:26:55.764 And it revolutionized the therapy of syphilis. 00:26:56.147 --> 00:26:59.150 In a 1915 medical textbook, it states, 00:27:00.685 --> 00:27:02.971 pregnant syphilitic women should be given 4 or 5 00:27:02.971 --> 00:27:05.423 injections of solverson as soon as conception is known 00:27:05.423 --> 00:27:08.610 to have occurred, and mercury continued throughout the pregnancy. 00:27:09.861 --> 00:27:12.147 So this actually is telling us 00:27:12.147 --> 00:27:15.900 that Solverson was, a great treatment, but it was not a, it was not a cure. 00:27:15.900 --> 00:27:18.887 They were actually still using mercury. 00:27:19.921 --> 00:27:21.956 So Alexander Fleming 00:27:21.956 --> 00:27:25.310 was one of the first physicians to administer solverson in England. 00:27:25.577 --> 00:27:28.530 And he got such a busy practice from patients 00:27:28.530 --> 00:27:32.250 with the venereal disease that, he got this nickname, private. 00:27:32.250 --> 00:27:34.135 606 from administering the combat. 00:27:34.135 --> 00:27:38.723 In 606, when World War One broke out, he saw the soldiers 00:27:38.723 --> 00:27:42.861 dying from infections, staph, strep, pneumococcal infections. 00:27:43.044 --> 00:27:47.449 And he really wanted a cure, just as Solverson was to treat syphilis. 00:27:47.449 --> 00:27:50.452 He wanted something that could treat these infections and save these soldiers. 00:27:51.086 --> 00:27:53.038 So he began experimenting. 00:27:53.038 --> 00:27:57.692 And in his lab, he would grow staff on on petri dishes. 00:27:57.842 --> 00:28:01.713 But his lab was pretty messy, and he piled a bunch of petri dishes with staff 00:28:01.713 --> 00:28:04.165 growing on them in the sink. Went on vacation. 00:28:04.165 --> 00:28:06.451 When he came back, he was looking through his plates 00:28:06.451 --> 00:28:09.087 and and he found mold growing on them with this. 00:28:09.087 --> 00:28:12.090 But there was this particularly funny effect here. 00:28:12.173 --> 00:28:16.678 The mold was causing a zone of inhibition, and where the staff wouldn't grow. 00:28:17.011 --> 00:28:20.665 And actually over, over here is even more impressive, but maybe harder to see. 00:28:20.665 --> 00:28:23.718 This is from his actual paper that he published with 00:28:23.718 --> 00:28:27.272 the mold is killing the colonies of stuff that were already there. 00:28:27.772 --> 00:28:30.775 This mold turned out to be the Penicillium species, 00:28:31.109 --> 00:28:34.729 so he presented on his findings in 1929. 00:28:34.729 --> 00:28:37.532 In the British Journal of Experimental Pathology. 00:28:37.532 --> 00:28:41.453 But like many revolutionary discoveries in medicine, it went largely 00:28:41.453 --> 00:28:42.771 ignored for some time. 00:28:45.023 --> 00:28:46.307 It was until World War two 00:28:46.307 --> 00:28:49.310 that there was a revitalized interest in developing an antibiotic. 00:28:49.310 --> 00:28:52.347 And these two biochemist, Howard Florian Ernst Chain 00:28:52.380 --> 00:28:55.366 picked up where Fleming had left off. 00:28:55.366 --> 00:28:58.203 They began experimenting again with the Penicillium mold, 00:28:58.203 --> 00:29:01.706 and they injected the isolate in live mice. 00:29:02.307 --> 00:29:04.159 And it actually worked. 00:29:04.159 --> 00:29:07.162 It was carrying infections, so they started treating humans with it. 00:29:07.579 --> 00:29:10.949 It became very popular, but they couldn't make enough of this compound. 00:29:10.949 --> 00:29:13.351 They didn't know how to grow it and make it well enough. 00:29:13.351 --> 00:29:17.789 And, they would treat the patient with the penicillin and then collect 00:29:17.789 --> 00:29:21.509 the patient's urine to give the metabolized drug back to the patient. 00:29:22.794 --> 00:29:25.380 So they really need a better way to manufacture this drug. 00:29:25.380 --> 00:29:28.950 So Florey traveled to the U.S., and he solicited help from 00:29:29.300 --> 00:29:33.438 an agricultural research center in Peoria, Illinois, where they were experienced 00:29:33.438 --> 00:29:34.939 with using fermentation. 00:29:34.939 --> 00:29:38.460 And they agree with the Penicillium mold on corn and penicillin. 00:29:38.460 --> 00:29:40.378 Just loved the corn. 00:29:40.378 --> 00:29:42.597 It just it made a 500 times yield. 00:29:42.597 --> 00:29:44.182 And they've been able to make back home. 00:29:45.300 --> 00:29:46.584 And at that 00:29:46.584 --> 00:29:50.722 point the United States entered World War two, War two, and they encouraged, 00:29:50.872 --> 00:29:53.875 chemical companies to begin making penicillin. 00:29:54.959 --> 00:29:57.529 By the time the war ended, the United States was producing 00:29:57.529 --> 00:30:00.532 650 billion units of penicillin a month. 00:30:02.517 --> 00:30:03.384 So penicillin 00:30:03.384 --> 00:30:06.387 has been arguably the world's most effective light. 00:30:06.621 --> 00:30:09.624 And it revolutionized the defense. 00:30:10.191 --> 00:30:13.428 It began using it for syphilis in 1943. 00:30:13.428 --> 00:30:16.431 And it's so effective that we actually still use it today. 00:30:16.531 --> 00:30:19.517 It caused a dramatic drop in the prevalence of syphilis. 00:30:21.169 --> 00:30:22.287 The recommended treatment 00:30:22.287 --> 00:30:26.424 for primary and secondary syphilis is to give one shot of Benzedrine, 00:30:26.424 --> 00:30:30.328 penicillin G, 2.4 million units intramuscularly. 00:30:32.480 --> 00:30:35.300 So this, brings us to a darker 00:30:35.300 --> 00:30:38.820 time in the history of, medical establishment, the United States. 00:30:39.287 --> 00:30:41.456 We're going to talk about some trials 00:30:41.456 --> 00:30:45.243 that were conducted on patients with syphilis in the US and abroad, 00:30:45.243 --> 00:30:49.280 but both were by United States researchers and funded by the United States. 00:30:50.031 --> 00:30:54.502 The first is the Tuskegee, Alabama study, which you may have heard of. 00:30:54.502 --> 00:30:56.304 It's pretty infamous. 00:30:56.304 --> 00:31:00.625 In 1932, the US Public Health Service began this study. 00:31:01.793 --> 00:31:02.927 It was called the Tuskegee 00:31:02.927 --> 00:31:05.930 Study of Untreated Syphilis in the Negro Male. 00:31:06.898 --> 00:31:11.753 They had 600 people enrolled, 399 were illiterate 00:31:11.903 --> 00:31:16.758 men, African-American men with syphilis, and 201 uninfected controls. 00:31:17.275 --> 00:31:19.561 It was originally supposed to last six months, 00:31:19.561 --> 00:31:23.581 and they started the study with the idea they needed to prove what the natural 00:31:23.581 --> 00:31:27.769 history of the progression of the disease untreated was, to be able to, 00:31:28.469 --> 00:31:31.439 get more funding to, to then treat the men. 00:31:31.439 --> 00:31:34.075 But the funding never came and they didn't end the study. 00:31:34.075 --> 00:31:36.978 They just kept the study going indefinitely. 00:31:36.978 --> 00:31:39.414 The problem with this study was they didn't inform 00:31:39.414 --> 00:31:40.648 the men of what was going on. 00:31:40.648 --> 00:31:42.750 There was no informed consent. 00:31:42.750 --> 00:31:46.404 They told the men that they were being treated for bad blood. 00:31:46.671 --> 00:31:50.491 This was a local term for fatigue, anemia, syphilis, 00:31:50.491 --> 00:31:52.143 anything that made you feel bad pretty much. 00:31:53.428 --> 00:31:55.980 They weren't exactly truthful about what was going on. 00:31:55.980 --> 00:31:57.715 What they gave them in for participating 00:31:57.715 --> 00:32:01.519 was free meals, free medical exams, and burial insurance. 00:32:01.519 --> 00:32:03.388 When they did pass away, 00:32:03.388 --> 00:32:07.141 the researchers in the Tuskegee study, they even solicited, 00:32:08.209 --> 00:32:11.479 help from the local physicians so that they would not treat them 00:32:11.479 --> 00:32:14.482 in even when treatments for syphilis were available. 00:32:14.482 --> 00:32:17.268 They knew these men were in the study and they were not allowed. 00:32:17.268 --> 00:32:20.271 They agreed to to withhold treatment from the men. 00:32:21.356 --> 00:32:25.109 Even in 1947, when penicillin clearly became the drug of choice 00:32:25.109 --> 00:32:28.379 and was used quite effectively and was widely available, the researchers 00:32:28.379 --> 00:32:31.432 intentionally denied it to these subjects to continue the study. 00:32:32.483 --> 00:32:35.253 In 1968, there was a single paper published 00:32:35.253 --> 00:32:38.690 that criticized ethics of the study, but not much happened about it. 00:32:38.990 --> 00:32:42.360 The CDC was actually in charge of the study at that time. 00:32:42.360 --> 00:32:47.632 In 1969, they did, an inquiry into the study. 00:32:47.632 --> 00:32:50.151 They decided that it did need to continue. 00:32:50.151 --> 00:32:51.502 And they solicited support 00:32:51.502 --> 00:32:54.889 from the local chapters of the American Medical Association 00:32:55.189 --> 00:32:59.610 and the National Medical Association, which is a black medical society. 00:33:00.928 --> 00:33:01.579 It wasn't until 00:33:01.579 --> 00:33:05.750 1962 that someone who had been trying to take the study down for a while 00:33:05.783 --> 00:33:10.338 published in the national press a story, and it made widespread news 00:33:10.972 --> 00:33:15.410 that the study was finally criticized, and the study ended in 1972. 00:33:17.311 --> 00:33:18.896 It wasn't until 1997 00:33:18.896 --> 00:33:21.899 that an apology was offered to these men by Bill Clinton. 00:33:22.467 --> 00:33:25.319 He said to the survivors, 00:33:25.319 --> 00:33:29.007 to the wives and family members, the children and the grandchildren, 00:33:29.273 --> 00:33:33.444 I say, what you know, no power on earth can give you back the lives lost, 00:33:33.828 --> 00:33:37.398 the pain suffered, the years of internal torment and anguish. 00:33:37.849 --> 00:33:39.617 What was done cannot be undone. 00:33:39.617 --> 00:33:41.419 But we can end the silence. 00:33:41.419 --> 00:33:43.137 We can stop turning our heads away. 00:33:43.137 --> 00:33:47.608 We can look at you in the eye and finally say on behalf of the American people, 00:33:47.959 --> 00:33:50.962 what the United States government did was shameful. 00:33:51.229 --> 00:33:52.046 And I'm sorry. 00:33:53.247 --> 00:33:54.832 This is Bill Clinton with one 00:33:54.832 --> 00:33:57.835 of the final survivors of the Tuskegee study here. 00:34:00.738 --> 00:34:01.856 Unfortunately, recently 00:34:01.856 --> 00:34:04.859 in the last couple of years, there was another study uncovered. 00:34:05.426 --> 00:34:10.648 One of the researchers on the Tuskegee study was John Charles Cutler, 00:34:10.648 --> 00:34:12.600 a Public Health service researcher, 00:34:12.600 --> 00:34:16.070 and he worked at the University of Pittsburgh as one of their deans. 00:34:16.337 --> 00:34:19.757 Subsequently, when he passed away, he donated all of his papers 00:34:20.158 --> 00:34:21.359 to the university. 00:34:21.359 --> 00:34:24.512 And it was going through these papers that discovered 00:34:24.662 --> 00:34:27.648 he was involved in another study in Guatemala. 00:34:28.983 --> 00:34:33.121 This was from 1946 to 1948, and it was sponsored by the Public Health 00:34:33.121 --> 00:34:36.958 Service, National Institutes of Health, World Health Organization. 00:34:36.958 --> 00:34:38.609 It was called something different at the time. 00:34:38.609 --> 00:34:42.296 The Guatemalan government was also, complicit in the study. 00:34:42.947 --> 00:34:46.167 In this study, they actually infected people with syphilis. 00:34:46.167 --> 00:34:49.487 They used prostitutes to try and infect prison inmates, insane 00:34:49.487 --> 00:34:53.241 asylum people, and soldiers in the Guatemalan army. 00:34:54.325 --> 00:34:55.877 But it wasn't particularly affected. 00:34:55.877 --> 00:34:56.694 Like I said earlier, 00:34:56.694 --> 00:35:00.198 there's only 30 to 60% transmission rate through sexual contact. 00:35:00.498 --> 00:35:02.967 So they decided to try something else. 00:35:02.967 --> 00:35:07.338 And they actually, infected people with direct inoculations 00:35:07.338 --> 00:35:12.243 made from syphilis bacteria poured into the men's penises and on forearms 00:35:12.243 --> 00:35:15.530 and faces that were slightly abraded or in a few cases, 00:35:15.530 --> 00:35:18.533 their spinal punctures. 00:35:18.866 --> 00:35:21.903 Approximately 1300 people were infected in this study, 00:35:22.937 --> 00:35:25.490 including some orphan children, 00:35:25.490 --> 00:35:28.493 and the results were never published. 00:35:29.760 --> 00:35:32.747 Charles Cutler, supervisor 00:35:33.080 --> 00:35:34.849 Thomas Perrin, the U.S. 00:35:34.849 --> 00:35:37.902 Surgeon General at the time, knew this was bad, but 00:35:38.553 --> 00:35:41.722 he said, you know, we couldn't do such an experiment in this country. 00:35:42.089 --> 00:35:44.942 But he didn't try and stop it. 00:35:44.942 --> 00:35:47.478 And that's why Cutler chose to do the study in Guatemala. 00:35:47.478 --> 00:35:49.997 He knew it wouldn't fly in the United States. 00:35:49.997 --> 00:35:53.634 One of his other superiors is Public Health Service physician Archie Arnold 00:35:53.634 --> 00:35:57.688 said, I am a bit, in fact, more than a bit leery of the experiment 00:35:57.688 --> 00:35:59.190 with the insane people. 00:35:59.190 --> 00:36:02.360 They cannot give consent, do not know what is going on, 00:36:02.360 --> 00:36:05.363 and if some good organization got wind of the work, 00:36:05.363 --> 00:36:06.747 they would raise a lot of smoke. 00:36:07.732 --> 00:36:08.883 That's kind of what happened. 00:36:08.883 --> 00:36:13.037 But it was until 2010 that, the Obama administration, 00:36:13.788 --> 00:36:16.490 gave an apology for what happened in Guatemala. 00:36:16.490 --> 00:36:19.493 They apologized to the president of Guatemala, 00:36:20.661 --> 00:36:24.048 Secretary of State Hillary Clinton and Health and Human Services 00:36:24.048 --> 00:36:27.168 Secretary Kathleen Sebelius put out this announcement. 00:36:27.768 --> 00:36:30.922 Although these events occurred more than 64 years ago, 00:36:31.255 --> 00:36:34.375 we are outraged that such reprehensible, reprehensible 00:36:34.375 --> 00:36:37.378 research could have occurred under the guise of public health. 00:36:38.362 --> 00:36:40.948 And actually, just this month, in April, 00:36:40.948 --> 00:36:43.801 the American Sexually Transmitted Disease Association 00:36:43.801 --> 00:36:45.686 renamed their most prestigious award, 00:36:45.686 --> 00:36:48.689 which had been previously called the Thomas Perrin Award. 00:36:49.106 --> 00:36:51.959 This guy. 00:36:51.959 --> 00:36:53.761 They decided to rename it 00:36:53.761 --> 00:36:56.747 the Astor Distinguished Career Award. 00:36:58.349 --> 00:37:01.469 So these studies show a gross abuse of trust 00:37:01.469 --> 00:37:04.472 by the medical profession, and it raised severe controversy. 00:37:05.389 --> 00:37:10.044 And it led to big changes in how we treat patients in clinical trials. 00:37:11.462 --> 00:37:11.929 It led to the 00:37:11.929 --> 00:37:16.517 1979 Belmont Report and a requirement for institutional review boards 00:37:16.517 --> 00:37:20.871 to approve any subject on human, any, any research on human subjects 00:37:21.589 --> 00:37:25.343 and to get informed consent from anyone participating in a research study 00:37:25.343 --> 00:37:28.346 to make sure they understand what they are agreeing to, 00:37:28.346 --> 00:37:31.232 what's going to be done to them, and what they're being compensated for. 00:37:31.232 --> 00:37:33.651 If anything. 00:37:33.651 --> 00:37:37.221 So that brings us back to today and how we diagnose syphilis. 00:37:37.471 --> 00:37:40.458 I'm going to go through the algorithms 00:37:40.558 --> 00:37:41.692 for diagnosing. 00:37:41.692 --> 00:37:44.695 And also, each of the different tests that we do. 00:37:50.785 --> 00:37:52.670 It's complicated to diagnose syphilis 00:37:52.670 --> 00:37:56.340 because we can't culture the organism outside of a live animal. 00:37:56.340 --> 00:37:57.892 In fact. 00:37:57.892 --> 00:38:01.946 So the types of tests that we do for syphilis are based on serology, on 00:38:02.179 --> 00:38:06.150 or detecting antibodies, either specifically to T pallidum 00:38:06.417 --> 00:38:09.587 or antibodies to other substances that are produced in the body 00:38:09.737 --> 00:38:11.839 when there is a syphilis infection. 00:38:11.839 --> 00:38:15.109 So these are called non triple animal tests or triple animal tests 00:38:15.326 --> 00:38:18.896 based on what the antigen in it is and whether it actually comes from T pallidum 00:38:18.896 --> 00:38:20.031 or if it is something else. 00:38:21.032 --> 00:38:21.332 And there 00:38:21.332 --> 00:38:24.318 are two algorithms used for screening and diagnosis. 00:38:24.318 --> 00:38:27.888 There is the traditional algorithm which the CDC currently recommends, but 00:38:27.888 --> 00:38:31.309 they also support the reverse algorithm, which makes some sense in 00:38:31.559 --> 00:38:34.562 in some cases, 00:38:34.712 --> 00:38:38.182 the non animal tests are the Rapid Plasma 00:38:38.182 --> 00:38:42.019 Reagent Test and the Venereal Disease Research Laboratory. 00:38:42.019 --> 00:38:45.506 Vdara recognized that so that we did on our patient. 00:38:47.842 --> 00:38:51.262 The antigen in both of these cases is cardio light in. 00:38:51.262 --> 00:38:54.298 And this is not an antigen that comes from T pallidum, 00:38:54.448 --> 00:38:55.649 but it's an antigen 00:38:55.649 --> 00:38:58.769 that's produced in the body when there is a T pallidum infection. 00:38:58.953 --> 00:39:00.421 It's a lipid. 00:39:00.421 --> 00:39:03.541 It's released from cell membranes that are cells are being destroyed. 00:39:03.841 --> 00:39:06.827 And in this case it's actually isolated from cow heart. 00:39:06.861 --> 00:39:10.031 But, what's being detected is antibodies against the reagent. 00:39:10.031 --> 00:39:13.034 And when the person is having that active destruction of cells 00:39:13.167 --> 00:39:17.455 by syphilis infection, they produce antibodies to cardio light, 00:39:17.455 --> 00:39:20.458 then called reagents with the antibodies are called. 00:39:21.359 --> 00:39:24.528 The good thing about these tests is that they can catch an active infection 00:39:25.279 --> 00:39:27.982 or to monitor titers from therapy, because the tears 00:39:27.982 --> 00:39:31.168 will change depending on how active the infection is. 00:39:32.453 --> 00:39:34.789 There are some false positives that can occur with this test, 00:39:34.789 --> 00:39:38.659 because any kind of destruction of cells could potentially cause a false positive, 00:39:39.060 --> 00:39:44.432 including HIV, herpes, malaria, ivy, drug use, 00:39:44.782 --> 00:39:48.352 lupus, rheumatoid arthritis, pregnancy, leprosy, 00:39:48.619 --> 00:39:51.622 and some other things can also cause false positives with these tests. 00:39:53.090 --> 00:39:55.342 So therefore we always follow up 00:39:55.342 --> 00:39:58.345 with a confirmatory test 00:39:58.579 --> 00:40:01.048 for the R and the VDL. 00:40:01.048 --> 00:40:03.150 The method is very similar. 00:40:03.150 --> 00:40:05.102 It's an agglutination reaction. 00:40:05.102 --> 00:40:09.390 So you have the patient's serum which contains antibodies 00:40:09.390 --> 00:40:13.577 potentially the antigen which is cardio light in the lipid antigen. 00:40:14.011 --> 00:40:17.214 Mixing it together with a chromo. 00:40:17.214 --> 00:40:21.168 Then this is making the reaction visible when it all clumps together, 00:40:22.403 --> 00:40:24.388 you can see an agglutination 00:40:24.388 --> 00:40:29.877 reaction and the PR is visible to the naked eye, whereas the VDL requires 00:40:29.927 --> 00:40:34.131 to look through a microscope to see the microscopic formulation reaction. 00:40:34.548 --> 00:40:36.383 It's non-reactive. It looks like this. 00:40:36.383 --> 00:40:40.321 And then you see this clumping up when there is a reaction and antibodies 00:40:40.321 --> 00:40:40.821 are present. 00:40:44.992 --> 00:40:45.626 Now the 00:40:45.626 --> 00:40:48.629 animal tests include the fluorescent chup, 00:40:48.662 --> 00:40:54.084 animal antibody, absorbed FTA abs, the one that we use as a confirmation 00:40:54.084 --> 00:40:57.121 test in our patient, the Troponin Paladin 00:40:57.121 --> 00:41:00.107 particle agglutination assay. TPA. 00:41:00.407 --> 00:41:04.111 There's also enzyme immunoassays and Kamiya luminescence immunoassays. 00:41:04.728 --> 00:41:07.097 And in all of these, the antigen is 00:41:07.097 --> 00:41:10.100 actually T pallidum in some form. 00:41:10.284 --> 00:41:13.587 And it detects specific antibodies against T pallidum. 00:41:14.388 --> 00:41:16.740 When a patient's been infected at any point in their life, 00:41:16.740 --> 00:41:20.578 they'll continue to be positive for these antibodies. 00:41:20.694 --> 00:41:25.232 So it means not distinguishing between an infection that has been treated 00:41:26.817 --> 00:41:28.469 for the FGA, ABS test 00:41:28.469 --> 00:41:31.472 fluorescent type animal antibody absorbed. 00:41:31.489 --> 00:41:35.125 This is using an antigen is all bacteria. 00:41:35.125 --> 00:41:39.363 The whole company and it's been isolated from fireflies 00:41:39.597 --> 00:41:42.983 rabbit testicular tissue that has been infected with T pallidum. 00:41:44.301 --> 00:41:45.503 It also uses an absorbent. 00:41:45.503 --> 00:41:48.355 This is hence the ABS portion of the name. 00:41:48.355 --> 00:41:52.826 The absorbent is a non pathogenic and this is going to pull out antibodies 00:41:52.826 --> 00:41:54.261 that anybody may have. 00:41:54.261 --> 00:41:57.264 Other animals in the environment that are not causing illness, 00:41:58.048 --> 00:42:00.301 that will lower the rate of false positives. 00:42:00.301 --> 00:42:04.471 And then a fluorophore labeled secondary antibody is going to bind. 00:42:04.471 --> 00:42:06.207 If the patient has antibodies 00:42:06.207 --> 00:42:10.127 and produces a visible reaction visible under a fluorescent microscope. 00:42:10.628 --> 00:42:13.964 But this test does not have very good specificity compared with the other strep 00:42:13.998 --> 00:42:14.965 animal tests. 00:42:14.965 --> 00:42:19.203 It can have false positives in lupus, pregnancy, leprosy, other things. 00:42:19.553 --> 00:42:23.490 So it's it's also very subjective, requires a lot of training 00:42:23.490 --> 00:42:26.911 for the technicians who read whether this is positive or negative. 00:42:26.911 --> 00:42:30.748 And so for that reason, it is no longer recommended in either of algorithms. 00:42:32.666 --> 00:42:33.000 Now, the 00:42:33.000 --> 00:42:37.104 TPA is the Japanese Paladin particle agglutination assay. 00:42:37.404 --> 00:42:41.875 And this is using gelatin particles that have been sensitized with cheap antigen. 00:42:42.626 --> 00:42:45.663 And when you put them together with the patient's serum 00:42:45.663 --> 00:42:48.782 containing antibodies against T pallidum, 00:42:48.782 --> 00:42:51.869 it causes this agglutination reaction. 00:42:51.869 --> 00:42:56.123 And when it's in the little wells here, it actually forms a mat on the bottom. 00:42:56.123 --> 00:43:01.645 And you can see this here where it is the positive reaction 00:43:02.246 --> 00:43:05.816 when there's no patient and no antibodies in the patient sample, 00:43:06.300 --> 00:43:09.570 the gelatin particles will just sort of clump 00:43:09.570 --> 00:43:12.856 up on the bottom of the well and look like a little button here. 00:43:12.856 --> 00:43:15.859 So that's an action 00:43:16.043 --> 00:43:18.295 for the EIA and CIA. 00:43:18.295 --> 00:43:21.498 These are both detecting those specific antibodies to T pallidum. 00:43:21.682 --> 00:43:25.586 And there are some some pros to starting with with this kind of testing. 00:43:25.586 --> 00:43:27.571 Mostly because it's really easy to do. 00:43:27.571 --> 00:43:30.140 It's automated good for big labs high throughput. 00:43:30.140 --> 00:43:31.892 It's low cost. 00:43:31.892 --> 00:43:33.777 You can do large volumes. 00:43:33.777 --> 00:43:35.479 And it can also catch early syphilis. 00:43:35.479 --> 00:43:37.831 If there hasn't been much destruction of cells yet, 00:43:37.831 --> 00:43:40.818 you're not going to see much of the reagent. 00:43:40.818 --> 00:43:43.187 And you may have a negative or PRV DRL. 00:43:44.605 --> 00:43:47.791 The cons of using Eisai is that it can't necessarily 00:43:47.791 --> 00:43:50.477 distinguish between the treated disease and the untreated disease. 00:43:50.477 --> 00:43:53.480 You'll still be positive even if it's been treated 00:43:54.348 --> 00:43:59.069 this, because of the ease of use, the low cost, high volume pros. 00:43:59.269 --> 00:44:00.954 It's recommended as the screening. 00:44:00.954 --> 00:44:03.891 The initial screening tests in the in Europe. 00:44:03.891 --> 00:44:06.360 And this is, part of the reverse 00:44:06.360 --> 00:44:09.363 algorithm which has been adopted in Europe 00:44:09.380 --> 00:44:11.849 for the, the EIA. 00:44:11.849 --> 00:44:14.718 You have a well with the antigen T pallidum. 00:44:14.718 --> 00:44:15.753 It's stuck to the bottom. 00:44:15.753 --> 00:44:19.590 And then you put in the patient sample, which if it contains antibodies 00:44:19.590 --> 00:44:24.678 against them here the patient's antibodies are going to bind to the antigen. 00:44:25.079 --> 00:44:27.047 The secondary antibody is linked. 00:44:27.047 --> 00:44:30.651 The enzyme linked portion is going to 00:44:31.402 --> 00:44:34.038 it's going to bind to the patient in a body. 00:44:34.038 --> 00:44:38.125 And when you add a substrate it's when you produce a reaction that is visible. 00:44:38.659 --> 00:44:43.497 Or it may produce, the chemical luminescence immunoassay, it will produce light. 00:44:45.499 --> 00:44:45.933 The two 00:44:45.933 --> 00:44:49.670 algorithms that we use to screen for and diagnose syphilis 00:44:49.670 --> 00:44:53.190 are the traditional, which is currently recommended by the CDC. 00:44:53.757 --> 00:44:56.160 And the reverse algorithm, 00:44:56.160 --> 00:45:00.264 the traditional is going to start with a non top animal test. 00:45:00.264 --> 00:45:03.267 That's going to be your Rtpcr or VDL. 00:45:04.468 --> 00:45:07.471 And then you confirm with the trip animal test which will tell you 00:45:08.338 --> 00:45:11.341 if it the first one was a false positive or not. 00:45:11.692 --> 00:45:14.428 And this is good at detecting the active infection, 00:45:14.428 --> 00:45:17.431 but it can miss the late late in infection. 00:45:17.481 --> 00:45:19.533 There may not be much destruction going on. 00:45:19.533 --> 00:45:22.136 And so you may not have much reagent detected. 00:45:22.136 --> 00:45:24.505 You can miss a latent infection in this way 00:45:24.505 --> 00:45:27.508 because you would stop after the first step. 00:45:28.008 --> 00:45:31.612 For the reverse, we begin with the EIA or CA is what's recommended, 00:45:31.612 --> 00:45:35.749 and then follow up with the animal test, which it's recommended to use the R. 00:45:36.333 --> 00:45:38.302 And this is good for the high throughput screening, 00:45:38.302 --> 00:45:41.305 maybe for a screening of blood supply, things like that. 00:45:41.672 --> 00:45:44.091 And it can catch a late infection 00:45:44.091 --> 00:45:46.527 or an early infection, or if you really want to know 00:45:46.527 --> 00:45:49.196 if the patient was ever infected, this might be a way to go, 00:45:49.196 --> 00:45:51.532 but it can't differentiate the treated from untreated. 00:45:53.300 --> 00:45:56.186 Here are the two algorithms. 00:45:56.186 --> 00:45:58.222 There's, the traditional, which. 00:45:58.222 --> 00:46:02.392 I'm sorry if you can't read this, this is the the best, graphic I have. 00:46:02.876 --> 00:46:05.062 It starts with r r. 00:46:05.062 --> 00:46:08.732 If that's positive, it's recommended to do the TPA. 00:46:08.932 --> 00:46:14.271 Or you could do another trap animal tests such as the EIA or CIA. 00:46:14.788 --> 00:46:18.509 If that's positive, the patient is diagnosed as having syphilis. 00:46:19.042 --> 00:46:22.946 If it's negative it was probably the first was probably a false positive. 00:46:23.547 --> 00:46:27.768 In the reverse sequence, we start always with the EIA or CIA. 00:46:28.552 --> 00:46:31.555 And if that's positive 00:46:31.638 --> 00:46:34.291 then you go on to do the PR. 00:46:34.291 --> 00:46:38.245 And if the PR is positive you can say yes, the patient has syphilis here. 00:46:38.245 --> 00:46:39.329 It says past or present. 00:46:39.329 --> 00:46:41.999 I think present would be 00:46:41.999 --> 00:46:43.050 if it was past. 00:46:43.050 --> 00:46:45.269 Maybe they're undergoing treatment at this time. 00:46:46.737 --> 00:46:49.706 So if the PR is negative you have discordant results. 00:46:49.706 --> 00:46:52.826 You've got EIA positive or negative. What. 00:46:52.826 --> 00:46:53.477 What does that mean? 00:46:53.477 --> 00:46:57.231 We want to know what's the likelihood that maybe the EIA was a false positive. 00:46:57.598 --> 00:46:59.249 Is it the treated infection whatnot. 00:46:59.249 --> 00:47:02.186 Well it'd be important to find out what the patient's history is. 00:47:02.186 --> 00:47:03.837 Have they ever been treated for syphilis? 00:47:03.837 --> 00:47:05.639 Have they ever had symptoms of syphilis? 00:47:05.639 --> 00:47:07.191 Could it be a treated infection 00:47:07.191 --> 00:47:10.194 or could it possibly be have gone to a latent infection? 00:47:10.194 --> 00:47:14.064 But so you want to follow up with a third test, a confirmatory test. 00:47:14.064 --> 00:47:17.451 If the PR is negative, you would always want to do a TPA. 00:47:17.668 --> 00:47:19.770 If that's positive, you can say yes. 00:47:19.770 --> 00:47:22.890 The patient likely either had syphilis and it was treated, 00:47:22.890 --> 00:47:26.660 or they have a latent infection now, and you should actually offer them 00:47:26.660 --> 00:47:29.179 treatment if they have not been treated in the past. 00:47:29.179 --> 00:47:34.651 If the TPP is negative, then you can feel safe in calling that EIA. 00:47:35.302 --> 00:47:38.038 An initial EIA that was positive, a false positive, 00:47:38.038 --> 00:47:40.374 but you'd still probably want to follow up with that patient 00:47:40.374 --> 00:47:43.460 to make sure that it wasn't just an extremely early infection. 00:47:44.928 --> 00:47:46.580 So back to our case. 00:47:46.580 --> 00:47:49.049 What screening algorithm did we use? 00:47:49.049 --> 00:47:52.052 We didn't exactly follow it exactly, but the 00:47:52.202 --> 00:47:55.188 we did BRL followed by FDA, ABS. 00:47:55.439 --> 00:47:57.808 So this is the traditional 00:47:57.808 --> 00:48:01.311 if we were doing this today, we would have started with either R 00:48:01.378 --> 00:48:04.915 and followed with a TPA recommended as the traditional. 00:48:06.500 --> 00:48:08.752 And how do we treat our patient and even remember 00:48:08.752 --> 00:48:11.755 what the treatment is for secondary syphilis? 00:48:14.391 --> 00:48:17.060 Penicillin? Yes. 00:48:17.060 --> 00:48:18.328 No. No. 00:48:18.328 --> 00:48:21.331 Mercury. 00:48:21.648 --> 00:48:24.117 Penicillin G I am 00:48:24.117 --> 00:48:27.120 you're just behind the times. 00:48:29.690 --> 00:48:32.009 So in conclusion, 00:48:32.009 --> 00:48:35.329 I think the syphilis is really had a profound effect on the practice 00:48:35.329 --> 00:48:38.332 of medicine throughout the ages since it's been first recognized. 00:48:38.515 --> 00:48:42.052 Also a big effect on art and literature. 00:48:42.052 --> 00:48:44.421 Poetry, 00:48:44.421 --> 00:48:46.189 drug development. 00:48:46.189 --> 00:48:49.559 We wouldn't have penicillin today if it hadn't been for syphilis. 00:48:50.727 --> 00:48:52.462 And it's led to 00:48:52.462 --> 00:48:55.582 lots of discoveries, new tests in laboratory medicine. 00:48:56.516 --> 00:48:58.969 And that's changed the way that we treat human subjects. 00:48:58.969 --> 00:49:02.222 And research, and led to there being protections in place 00:49:02.539 --> 00:49:05.509 for protecting human subjects. 00:49:05.509 --> 00:49:08.512 So does anybody have any questions? 00:49:08.762 --> 00:49:11.698 I have one more slide just for fun. 00:49:11.698 --> 00:49:15.802 There are lots of famous people throughout history with syphilis, including Hitler. 00:49:16.853 --> 00:49:21.325 He probably contracted syphilis in 1908 from a Jewish prostitute. 00:49:21.808 --> 00:49:25.495 He called it the Jewish disease, and he wrote about it extensively in Mein 00:49:25.495 --> 00:49:27.481 camp. 00:49:27.481 --> 00:49:30.467 So syphilis may have been responsible for the Second World War. 00:49:31.134 --> 00:49:33.503 But by the time by the end of the war, 00:49:33.503 --> 00:49:36.506 Hitler was just straight insane from syphilis. 00:49:37.074 --> 00:49:40.527 Other people who had Edward Shakespeare, Pope Alexander, 00:49:40.978 --> 00:49:44.881 Ivan the Terrible and the picture of him there murdering his son, 00:49:46.199 --> 00:49:48.318 Henry the Eighth, 00:49:48.318 --> 00:49:51.421 Hernan Cortez and Al Capone all had syphilis.