1 00:00:00,000 --> 00:00:12,980 Thanks for joining us again at the Canadian Breakpoint, a Canadian infectious diseases 2 00:00:12,980 --> 00:00:16,800 podcast by Canadian infectious diseases physicians. 3 00:00:16,800 --> 00:00:21,740 I'm Summer Stewart, here with Dr. Rupeena Purewal, pediatric infectious diseases specialist 4 00:00:21,740 --> 00:00:22,740 from Saskatoon. 5 00:00:22,740 --> 00:00:29,280 In this episode, we welcome Winnipeg microbiologist Dr. David Alexander to discuss disseminated 6 00:00:29,280 --> 00:00:30,720 gonorrhea infections. 7 00:00:30,720 --> 00:00:33,200 Dr. Purewal. 8 00:00:33,200 --> 00:00:37,000 Welcome to another episode of our podcast the Canadian Breakpoint. 9 00:00:37,000 --> 00:00:42,480 So today we have a very special guest with us, Dr. David Alexander, who's a PhD trained 10 00:00:42,480 --> 00:00:47,520 microbiologist with a long standing interest in the epidemiology of infectious diseases. 11 00:00:47,520 --> 00:00:54,040 For the past 15 years, he has worked in Canada's provincial public health laboratory system. 12 00:00:54,040 --> 00:00:57,840 He's currently based in Winnipeg and is an assistant professor with the Department of 13 00:00:57,840 --> 00:01:02,400 Medical Microbiology and Infectious Diseases at the University of Manitoba. 14 00:01:02,400 --> 00:01:10,600 Dr. Alexander's research encompasses diverse topics, including novel diagnostics, genomics, 15 00:01:10,600 --> 00:01:16,080 antibiotic resistant organisms, and the surveillance of bacterial pathogens that cause foodborne 16 00:01:16,080 --> 00:01:19,240 illnesses and sexually transmitted infections. 17 00:01:19,240 --> 00:01:21,520 So welcome, Dr. Alexander. 18 00:01:21,520 --> 00:01:22,520 Thank you. 19 00:01:22,520 --> 00:01:24,400 Thank you for the invitation and the introduction. 20 00:01:24,400 --> 00:01:25,440 Perfect. 21 00:01:25,440 --> 00:01:31,480 So today we're talking about a very important topic linked to sexually transmitted infections 22 00:01:31,480 --> 00:01:35,400 on disseminated gonococcal infections. 23 00:01:35,400 --> 00:01:41,360 And congratulations on your recent publication in the Journal of the American Sexually Transmitted 24 00:01:41,360 --> 00:01:44,100 Diseases. 25 00:01:44,100 --> 00:01:47,300 That's very exciting to see some of your work there. 26 00:01:47,300 --> 00:01:53,400 And so I guess before we kind of start talking a little bit about the study and all of your 27 00:01:53,400 --> 00:02:00,480 research results, why don't we give our audience a bit of a background on gonorrhea and disseminated 28 00:02:00,480 --> 00:02:02,680 gonococcal infections, including presentations? 29 00:02:02,680 --> 00:02:04,120 Of course. 30 00:02:04,120 --> 00:02:08,040 So gonorrhea is a sexually transmitted infection. 31 00:02:08,040 --> 00:02:13,320 It's caused by bacteria, nigeria gonorrhea, often just called the gonococcus. 32 00:02:13,320 --> 00:02:18,680 And in most Western nations, gonorrhea is considered the second most common bacterial 33 00:02:18,680 --> 00:02:23,140 sexually transmitted infection, second only to chlamydia. 34 00:02:23,140 --> 00:02:29,720 Like most sexually transmitted infections that most commonly present either, well, in 35 00:02:29,720 --> 00:02:30,720 your bits. 36 00:02:30,720 --> 00:02:35,640 So you have uncomfortable urination, dysuria, bleeding. 37 00:02:35,640 --> 00:02:39,600 There's lots of wonderful terms for your sexually transmitted infection. 38 00:02:39,600 --> 00:02:45,000 Gonorrhea is sometimes called the drip because you just have this discharge that leaks out. 39 00:02:45,000 --> 00:02:50,840 And yeah, I guess what one thinks of with sexually transmitted infections are infections 40 00:02:50,840 --> 00:02:55,520 in the penis or urethra, vagina or cervix, that sort of thing. 41 00:02:55,520 --> 00:03:00,480 However, the more work you do in the realm of especially gonorrhea, you realize that 42 00:03:00,480 --> 00:03:02,440 it will affect a lot of other nuchal membranes. 43 00:03:02,440 --> 00:03:09,680 So there's been increased recognition of proctitis from rectal infections, as well as pharyngitis 44 00:03:09,680 --> 00:03:10,680 from throat infections. 45 00:03:10,680 --> 00:03:16,280 And that's just really the bacteria will cause symptoms wherever it is introduced. 46 00:03:16,280 --> 00:03:21,040 And due to the wonderful and varied ways that people interact with each other and have sex, 47 00:03:21,040 --> 00:03:24,280 we see it in all sorts of different places. 48 00:03:24,280 --> 00:03:28,640 What was new to me before we really started this study was what's called disseminated 49 00:03:28,640 --> 00:03:30,840 gonococcal infection. 50 00:03:30,840 --> 00:03:36,320 And that is infections that occur inside your body, so systemic presentations where you 51 00:03:36,320 --> 00:03:44,600 have the bacteria in your blood or in your joints where they cause arthritis, joint pain. 52 00:03:44,600 --> 00:03:49,840 And even there's sort of the worst case scenario is when it can spread and lodge in organs. 53 00:03:49,840 --> 00:03:57,120 We've seen where we are in Manitoba, endocarditis, so heart infection, and even meningitis, brain 54 00:03:57,120 --> 00:03:58,120 infection. 55 00:03:58,120 --> 00:04:04,120 And that's unusual because even though gonorrhea has a cousin, nisteria meningitidis, that 56 00:04:04,120 --> 00:04:09,560 causes, as the name suggests, meningitis or brain infection, it's really uncommon for 57 00:04:09,560 --> 00:04:12,480 gonorrhea itself to do that. 58 00:04:12,480 --> 00:04:18,080 So definitely, I mean, there's multiple different presentations, as you mentioned, and really 59 00:04:18,080 --> 00:04:23,640 our focus today on disseminated gonococcal infections, because there hasn't been a lot 60 00:04:23,640 --> 00:04:29,360 of research to, even my knowledge, or even in our clinical world, identification of such 61 00:04:29,360 --> 00:04:33,480 cases like you mentioned, it's not as commonly spoken about. 62 00:04:33,480 --> 00:04:37,960 And so I guess what really sparked your interest in this topic? 63 00:04:37,960 --> 00:04:43,640 Well, working in the public health system in Canada, most provincial public health labs 64 00:04:43,640 --> 00:04:49,520 basically do province-wide screening for a whole variety of sexually transmitted infections. 65 00:04:49,520 --> 00:04:55,000 And that's really where I first encountered all of these diseases is as part of my routine 66 00:04:55,000 --> 00:04:57,920 work, looking at the rates of infection. 67 00:04:57,920 --> 00:05:02,840 And in the prairies, especially in Canada, the rates of infection are higher than in 68 00:05:02,840 --> 00:05:04,840 the rest of Canada. 69 00:05:04,840 --> 00:05:10,680 So yeah, so if you look at the history of sexually transmitted infections in Canada, 70 00:05:10,680 --> 00:05:16,440 there's really like a before HIV and after HIV world. 71 00:05:16,440 --> 00:05:24,640 And so it's remarkable to think that it's actually been now almost 40 years, like 1983, 72 00:05:24,640 --> 00:05:27,760 when the first tests for HIV really became available. 73 00:05:27,760 --> 00:05:34,160 And the AIDS epidemic was recognized, and there was this big push towards safer sex 74 00:05:34,160 --> 00:05:38,080 and all these other things that you're of a certain age, you grew up with during the 75 00:05:38,080 --> 00:05:39,800 80s and especially during the 90s. 76 00:05:39,800 --> 00:05:43,680 And these campaigns were really, really effective. 77 00:05:43,680 --> 00:05:46,720 And we saw plummeting rates of all sorts of diseases. 78 00:05:46,720 --> 00:05:52,440 Of course, HIV was the primary one because at the time it was a death sentence. 79 00:05:52,440 --> 00:05:55,600 And so you definitely didn't want to get HIV. 80 00:05:55,600 --> 00:06:01,260 But the same precautions work against syphilis, which came close to elimination and really 81 00:06:01,260 --> 00:06:03,720 dropped the rates of gonorrhea and chlamydia. 82 00:06:03,720 --> 00:06:09,160 So if you look at data that's available from, for example, the Public Health Agency of Canada, 83 00:06:09,160 --> 00:06:18,960 the rate of gonorrhea by about the year 2000 was maybe 25 cases per 100,000 people. 84 00:06:18,960 --> 00:06:21,320 So quite, quite low. 85 00:06:21,320 --> 00:06:29,720 By contrast, in Manitoba right now, we're about 10 times that, about 250 cases per 100,000. 86 00:06:29,720 --> 00:06:34,560 And what's remarkable is that most of that increase has happened in the last, well, really 87 00:06:34,560 --> 00:06:39,960 about since 2015, so the last five to 10 years is really when that rate has gone up. 88 00:06:39,960 --> 00:06:42,920 And we're not really sure why. 89 00:06:42,920 --> 00:06:49,680 We assume it has to do with changing behaviors and perhaps less concern because even for 90 00:06:49,680 --> 00:06:52,960 HIV now there's very effective treatment, so it's no longer death sentence. 91 00:06:52,960 --> 00:06:58,400 And certainly for things like gonorrhea, given uncomplicated case, currently we just use 92 00:06:58,400 --> 00:07:04,240 two drugs and one dose of each of those drugs and you're pretty much cured. 93 00:07:04,240 --> 00:07:08,560 So anyways, suffice to say when it comes to disseminated gonorrhea, if you look at historical 94 00:07:08,560 --> 00:07:15,280 literature, they would argue that two to 3% of cases might present a disseminated infection, 95 00:07:15,280 --> 00:07:17,920 so in your blood with arthritis. 96 00:07:17,920 --> 00:07:23,920 It's been difficult to actually figure out that exact number, that portion. 97 00:07:23,920 --> 00:07:29,640 But you know, if you're only seeing a thousand cases of gonorrhea a year and your DGI rate 98 00:07:29,640 --> 00:07:36,480 is two or 3%, you don't see very many of these cases, even if you're a practicing clinician. 99 00:07:36,480 --> 00:07:41,160 Whereas as soon as your rate of gonorrhea goes up, you expect to see more. 100 00:07:41,160 --> 00:07:44,360 But what we've really been concerned about and what started some of the research we're 101 00:07:44,360 --> 00:07:49,360 going to talk about has to do with the rate of the disseminated infection went up at a 102 00:07:49,360 --> 00:07:55,080 much faster rate, about three times faster than the overall rate of gonococcal infection. 103 00:07:55,080 --> 00:07:56,080 Okay. 104 00:07:56,080 --> 00:08:01,480 And the one thing you can say about disseminated gonorrhea is if you look through the microbiology 105 00:08:01,480 --> 00:08:06,320 literature, there's lots and lots of reports, lots of lots of case reports, and they always 106 00:08:06,320 --> 00:08:10,080 say, oh, this is a rare presentation of gonorrhea. 107 00:08:10,080 --> 00:08:14,080 But when you add up all these reports, it's actually not quite as uncommon as one would 108 00:08:14,080 --> 00:08:15,680 think. 109 00:08:15,680 --> 00:08:22,000 And so that's the other question that DogsR Research is, is the increase we're seeing 110 00:08:22,000 --> 00:08:27,040 just due to increased awareness that these infections can occur. 111 00:08:27,040 --> 00:08:28,040 Yeah. 112 00:08:28,040 --> 00:08:29,040 Yeah. 113 00:08:29,040 --> 00:08:35,480 So definitely having, you know, this on your radar as a clinician, I think you're more 114 00:08:35,480 --> 00:08:40,400 inclined to kind of look for infections. 115 00:08:40,400 --> 00:08:43,120 You're more inclined to send cultures. 116 00:08:43,120 --> 00:08:47,160 And I think we'll talk a little bit about that in your study as well as to how much 117 00:08:47,160 --> 00:08:53,560 is done, you know, diagnosed with PCR versus culture, which is sometimes a limitation when 118 00:08:53,560 --> 00:08:56,480 we're dealing with sexually transmitted infections. 119 00:08:56,480 --> 00:08:57,660 Yeah. 120 00:08:57,660 --> 00:09:01,800 So I guess without further ado, because I'm excited to hear a little bit more about your 121 00:09:01,800 --> 00:09:09,360 research, why don't we introduce your, you know, some of your research findings and talk 122 00:09:09,360 --> 00:09:11,840 a little bit about your abstract in the paper. 123 00:09:11,840 --> 00:09:12,840 Okay. 124 00:09:12,840 --> 00:09:17,760 So I should start by saying this research project's been going on for a while and it's 125 00:09:17,760 --> 00:09:19,480 gone through several stages. 126 00:09:19,480 --> 00:09:26,360 So really our initial interest was because, you know, 15 years ago, disseminated gonorrhea 127 00:09:26,360 --> 00:09:27,760 was very uncommon. 128 00:09:27,760 --> 00:09:33,640 We would, the lab, even though it screens, you know, tens of thousands of people per 129 00:09:33,640 --> 00:09:39,640 year and detects several thousand cases per year, disseminated gonococcal infections were 130 00:09:39,640 --> 00:09:40,640 very, very rare. 131 00:09:40,640 --> 00:09:46,280 We would see maybe two or three a year and some years there were none. 132 00:09:46,280 --> 00:09:48,760 And then, as I mentioned, the rate of that started going up. 133 00:09:48,760 --> 00:09:52,200 It was, you know, a dozen and then two dozen and three dozen a year. 134 00:09:52,200 --> 00:09:55,400 So it really caught our attention. 135 00:09:55,400 --> 00:10:01,840 And we were also getting contacted by physicians who were struggling to get a clear diagnosis 136 00:10:01,840 --> 00:10:07,640 because this is a sexually transmitted infection, the approved normal commercial and health 137 00:10:07,640 --> 00:10:13,960 Canada approved tests geared towards things like endocyclic swabs or urine samples, you 138 00:10:13,960 --> 00:10:17,160 know, things you normally would associate with sexually transmitted infection. 139 00:10:17,160 --> 00:10:23,440 But what was happening is these folks were showing up in the ER complaining about a sore 140 00:10:23,440 --> 00:10:25,520 elbow or a sore knee. 141 00:10:25,520 --> 00:10:30,080 And you know, you don't immediately think, oh, it must be a sexually transmitted infection 142 00:10:30,080 --> 00:10:33,040 if it's in your elbow or knee. 143 00:10:33,040 --> 00:10:37,640 So often in those cases, you would get a joint fluid draw. 144 00:10:37,640 --> 00:10:42,200 So you could draw a culture to see if you can grow other organisms associated with those 145 00:10:42,200 --> 00:10:48,160 sorts of infections here in floor like your strep and your staff and that sort of thing. 146 00:10:48,160 --> 00:10:52,760 But Neisseria gonorrhea is actually a tricky organism to grow. 147 00:10:52,760 --> 00:10:57,680 And unless you're using the right media, you're not going to catch it. 148 00:10:57,680 --> 00:11:03,520 And even if you are using the right media, you may not catch it all the time. 149 00:11:03,520 --> 00:11:07,240 And so we were being asked, are there better ways to diagnose it? 150 00:11:07,240 --> 00:11:12,960 And initially, we really weren't sure our standard method for diagnosing gonorrhea uses 151 00:11:12,960 --> 00:11:14,760 nucleic acid amplification. 152 00:11:14,760 --> 00:11:21,200 So think of like a PCR type test where you're detecting the nucleic acid from the organism 153 00:11:21,200 --> 00:11:24,520 itself and not you don't have to actually grow the bug. 154 00:11:24,520 --> 00:11:31,880 Neisseria gonorrhea was introduced probably about 15 years ago and is universally used 155 00:11:31,880 --> 00:11:35,040 now because it is so good. 156 00:11:35,040 --> 00:11:38,480 And really, when it was first introduced, there was a bump in the rate of gonorrhea, 157 00:11:38,480 --> 00:11:42,720 not because there was more gonorrhea around, but we were just so much better at detecting 158 00:11:42,720 --> 00:11:43,720 it. 159 00:11:43,720 --> 00:11:50,440 And even though it was initially designed for urine and the cervical and vaginal swabs, 160 00:11:50,440 --> 00:11:56,120 the standard tests we used have been expanded to include rectal swabs and throat swabs. 161 00:11:56,120 --> 00:12:00,360 And so we were thinking, well, if we're now finding this more commonly in joint fluid, 162 00:12:00,360 --> 00:12:02,960 why don't we just test the joint fluid? 163 00:12:02,960 --> 00:12:08,600 And so we did a study where we took about 170 samples collected over several months. 164 00:12:08,600 --> 00:12:13,800 And after they've been fully worked up by our routine microbiology procedures, microscopes, 165 00:12:13,800 --> 00:12:19,360 culture, and that sort of thing, we retested them using the nucleic acid amplification 166 00:12:19,360 --> 00:12:20,880 test. 167 00:12:20,880 --> 00:12:29,880 And we're quite surprised to see that even though we did grow a few samples by culture, 168 00:12:29,880 --> 00:12:36,320 culture only detected about 40% of the samples that were positive by nucleic acid amplification. 169 00:12:36,320 --> 00:12:44,480 Yeah, I mean, it wasn't a huge study, but we did test 170 samples of joint fluid. 170 00:12:44,480 --> 00:12:50,040 And we really leave to find how well our tests performed on the joint fluid samples, even 171 00:12:50,040 --> 00:12:54,120 though it wasn't a test necessarily designed for that. 172 00:12:54,120 --> 00:13:00,000 And so yeah, if you want our actual numbers from there, five samples grew, or we grew 173 00:13:00,000 --> 00:13:05,320 in Nigeria from five cultures, but there were actually 14 that were positive by nucleic 174 00:13:05,320 --> 00:13:07,320 acid amplification. 175 00:13:07,320 --> 00:13:12,560 And when we had an external lab retest some of those samples just to confirm our results, 176 00:13:12,560 --> 00:13:14,960 they did confirm. 177 00:13:14,960 --> 00:13:16,880 Basically this means that this is not an illusion. 178 00:13:16,880 --> 00:13:21,600 There really is a lot more disseminated gonorrhea out there than we were expecting. 179 00:13:21,600 --> 00:13:24,800 So that's really the first step is if you're going to look at infectious diseases, you 180 00:13:24,800 --> 00:13:27,960 need to test that will detect them. 181 00:13:27,960 --> 00:13:32,640 The next part we've moved into is really trying to understand is there something special about 182 00:13:32,640 --> 00:13:39,280 the bacteria that cause these diseases relative to what's normally circulating in where you 183 00:13:39,280 --> 00:13:40,280 are? 184 00:13:40,280 --> 00:13:43,800 Because that's always the question when it comes to infectious diseases, is it something 185 00:13:43,800 --> 00:13:47,240 about the bug or is it something about the host? 186 00:13:47,240 --> 00:13:52,560 And of course, there's all these reasons why some people may be more susceptible to infection 187 00:13:52,560 --> 00:13:54,520 than others. 188 00:13:54,520 --> 00:13:59,080 And really when we started this work, I thought, well, we're probably just looking at a population 189 00:13:59,080 --> 00:14:04,060 that is more susceptible or there's zone of access to healthcare or whatever reasons for 190 00:14:04,060 --> 00:14:08,960 which you wouldn't necessarily get treated right away and the gonorrhea would have time 191 00:14:08,960 --> 00:14:11,560 to spread. 192 00:14:11,560 --> 00:14:17,200 And so to address that component of the question, we use genome sequencing. 193 00:14:17,200 --> 00:14:24,200 I say that casually, but it's really taken a long time for genome sequencing technologies 194 00:14:24,200 --> 00:14:28,440 to really come to where they are today. 195 00:14:28,440 --> 00:14:33,720 I've been lucky enough to be involved with sequencing based approaches for a while now 196 00:14:33,720 --> 00:14:41,160 and the power that they provide is really quite remarkable because unfortunately, we've 197 00:14:41,160 --> 00:14:47,800 had so many cases lately and we've been able to isolate so many strains of gonorrhea. 198 00:14:47,800 --> 00:14:52,640 We really were able to do a pretty decent sized project and sequence about a hundred 199 00:14:52,640 --> 00:14:56,200 strains all from joints and blood sites. 200 00:14:56,200 --> 00:14:59,360 So all associated with disseminated gonorrhea. 201 00:14:59,360 --> 00:15:05,800 And so what we discovered when we sequenced them all and looked at them, they were more 202 00:15:05,800 --> 00:15:08,600 similar than we expected. 203 00:15:08,600 --> 00:15:13,720 Normally what happens with strains of any bacteria, if you take the time to what's called 204 00:15:13,720 --> 00:15:18,600 type them and look at the differences between them, you see all sorts of different types. 205 00:15:18,600 --> 00:15:22,920 I think people have sort of started to recognize this with COVID where every few months there 206 00:15:22,920 --> 00:15:28,200 seems to be a new type of COVID, an alpha or a delta or different kinds of omicron. 207 00:15:28,200 --> 00:15:35,280 And so there's this constant change in what the bacteria or the microbes look like. 208 00:15:35,280 --> 00:15:41,400 And yet when we looked at our gonorrhea strains, we only found five different types, even though 209 00:15:41,400 --> 00:15:47,120 we know that there are dozens, if not hundreds of different types of gonorrhea out there. 210 00:15:47,120 --> 00:15:53,400 More than that, when we looked at these five types, they all shared something called the 211 00:15:53,400 --> 00:15:59,080 poor B type, so poor B, it used to be called, I don't remember, protein one. 212 00:15:59,080 --> 00:16:03,560 It's basically a marker that we use when typing. 213 00:16:03,560 --> 00:16:07,560 And it's a really effective marker for typing because it has that perfect balance of it's 214 00:16:07,560 --> 00:16:10,920 something that every gonorrhea strain has. 215 00:16:10,920 --> 00:16:17,160 It's essential enough to the organism that it changes, that it's always going to be there, 216 00:16:17,160 --> 00:16:19,960 but it also can change. 217 00:16:19,960 --> 00:16:24,400 And it's the changes within between strains that we're actually looking at when we're 218 00:16:24,400 --> 00:16:25,400 typing organisms. 219 00:16:25,400 --> 00:16:31,480 But I don't want to get too technical, but the poor type we found is called poor 2206. 220 00:16:31,480 --> 00:16:37,000 And it was found in all five of the different, I guess, flavors or strains of gonorrhea that 221 00:16:37,000 --> 00:16:39,080 we were looking at. 222 00:16:39,080 --> 00:16:46,040 And it was present in over 90% of the strains that we actually did sequence. 223 00:16:46,040 --> 00:16:51,880 Now that's unusual because when we looked at a comparator group of strains in Canada 224 00:16:51,880 --> 00:16:57,440 that don't cause disseminated infection, poor B is present in maybe 2% of those. 225 00:16:57,440 --> 00:17:02,760 So even though it's only present in maybe 2% of what's out there in the world, it was 226 00:17:02,760 --> 00:17:08,600 in over 90% of the strains associated with disseminated gonorrhea. 227 00:17:08,600 --> 00:17:14,360 And that was a big surprise to me because I really thought it was probably a host associated 228 00:17:14,360 --> 00:17:15,360 factor. 229 00:17:15,360 --> 00:17:20,800 And then other sexually transmitted infections, it's individual behavior or susceptibilities 230 00:17:20,800 --> 00:17:27,160 or things like that that predispose you to infections and then sometimes nasty infections. 231 00:17:27,160 --> 00:17:29,800 And that's not the case with gonorrhea. 232 00:17:29,800 --> 00:17:30,800 Yeah. 233 00:17:30,800 --> 00:17:33,320 I was actually surprised to see that as well. 234 00:17:33,320 --> 00:17:41,080 I mean, classically, what we learn in med school and also when we're training is to 235 00:17:41,080 --> 00:17:47,240 when there are nyseria infections that are ongoing or persistent or recurrent nyseria 236 00:17:47,240 --> 00:17:52,640 types of infections, then usually host factors like complement deficiencies or if they're 237 00:17:52,640 --> 00:17:58,960 on certain immune suppressive drugs, those are the kind of areas that we focus on. 238 00:17:58,960 --> 00:18:01,480 Then likely the patient might have this. 239 00:18:01,480 --> 00:18:04,200 That's why they presented very severe with this. 240 00:18:04,200 --> 00:18:10,720 But I think it's always two-sided and it's similar to how you mentioned with, we've seen 241 00:18:10,720 --> 00:18:14,680 this with other infections, including COVID itself. 242 00:18:14,680 --> 00:18:18,680 We've seen very severe presentations, milder presentations. 243 00:18:18,680 --> 00:18:21,600 Sometimes it's host related, sometimes it's incidental. 244 00:18:21,600 --> 00:18:29,760 And so, but I think looking at the molecular level, especially with gonorrhea here, identifying 245 00:18:29,760 --> 00:18:36,040 a specific allele like this that is coming from 90% of your samples, I mean, definitely 246 00:18:36,040 --> 00:18:38,760 has a correlation with that severity. 247 00:18:38,760 --> 00:18:43,560 So that was a very interesting finding for myself as well. 248 00:18:43,560 --> 00:18:47,240 So of course, when you have a finding like this, you go back to the literature to see 249 00:18:47,240 --> 00:18:49,160 what else other people have seen. 250 00:18:49,160 --> 00:18:54,200 And in retrospect, we shouldn't have been quite so surprised because this Orbi allele 251 00:18:54,200 --> 00:18:58,640 has been associated with infections for a while. 252 00:18:58,640 --> 00:19:04,120 And we live in an era of molecular diagnostics and genomics and all this exciting stuff where 253 00:19:04,120 --> 00:19:09,480 sometimes we almost forget to look at the organism and just focused on the ACs and T's 254 00:19:09,480 --> 00:19:12,080 and G's on our computer screen. 255 00:19:12,080 --> 00:19:18,360 But if you actually go back to the bench or go back to sort of the classical microbiology 256 00:19:18,360 --> 00:19:24,320 where folks are growing strains and really looking at them, it turns out that for decades 257 00:19:24,320 --> 00:19:32,080 now it's been recognized that gonococcal isolates from disseminated infections actually are 258 00:19:32,080 --> 00:19:37,400 quite different from the run-of-the-mill things you typically see with what's called uncomplicated 259 00:19:37,400 --> 00:19:39,400 sexually transmitted infections. 260 00:19:39,400 --> 00:19:45,040 And so we're continuing to look and try to correlate some of these old phenotypic findings 261 00:19:45,040 --> 00:19:48,440 with what we can see in the genomics. 262 00:19:48,440 --> 00:19:51,400 And we know some are quite well characterized. 263 00:19:51,400 --> 00:19:57,640 For example, when you grow the disseminated strains on your agar plate that you see, and 264 00:19:57,640 --> 00:20:02,720 normally they have what's called a transparent colony phenotype, they're sort of clear, they're 265 00:20:02,720 --> 00:20:06,040 not sort of a solid dark opaque color. 266 00:20:06,040 --> 00:20:10,400 And originally that phenotype was called opacity. 267 00:20:10,400 --> 00:20:14,600 And so there's actually a protein called the OPA proteins that are now known to coat the 268 00:20:14,600 --> 00:20:21,960 outside of gonorrhea and change how the organism interacts with your immune system. 269 00:20:21,960 --> 00:20:26,600 Or B, which we've been focused on, is also something that's in the cell wall or the outer 270 00:20:26,600 --> 00:20:31,000 membrane of the bacteria and interacts with the immune system. 271 00:20:31,000 --> 00:20:36,480 And studies of Orbi have kind of revealed that it is actually able to interact with 272 00:20:36,480 --> 00:20:39,040 the complement system, which is something you mentioned. 273 00:20:39,040 --> 00:20:43,120 And so, I mean, briefly, I'm not an immunologist, but... 274 00:20:43,120 --> 00:20:46,920 Neither am I, so okay. 275 00:20:46,920 --> 00:20:50,080 But the complement system is part of your sort of innate immune system. 276 00:20:50,080 --> 00:20:57,840 If it sees a foreign invader, it basically targets that invader to be cleaned up by other 277 00:20:57,840 --> 00:20:58,840 components of the immune system. 278 00:20:58,840 --> 00:21:04,160 So it sort of tags or targets you and says, get rid of this thing. 279 00:21:04,160 --> 00:21:10,800 And what happens with gonorrhea, in part, do we think to the Orbi system, is that it 280 00:21:10,800 --> 00:21:12,880 basically shuts that down. 281 00:21:12,880 --> 00:21:17,120 It pulls this Jedi mind trick where it's like, oh, I'm not what you're looking for. 282 00:21:17,120 --> 00:21:22,120 It basically down-regulates the complement system so it's no longer being targeted. 283 00:21:22,120 --> 00:21:26,920 And the reason that's probably important is, you know, at the time the gonorrhea is doing 284 00:21:26,920 --> 00:21:28,200 this, it's already in your blood. 285 00:21:28,200 --> 00:21:29,920 It's already circulating through your system. 286 00:21:29,920 --> 00:21:30,920 Right. 287 00:21:30,920 --> 00:21:33,040 It can stop your immune system from taking it out. 288 00:21:33,040 --> 00:21:38,680 It gets that much more time to persist in your blood and to spread to your organs, be 289 00:21:38,680 --> 00:21:43,600 it your joints or your heart or wherever else it needs to go. 290 00:21:43,600 --> 00:21:48,760 When you look at the disseminate gonorrhea literature, all sorts of sites can be acted 291 00:21:48,760 --> 00:21:51,840 wherever the organisms land. 292 00:21:51,840 --> 00:21:58,680 Most commonly in your guys' study, the isolates were blood and synovial fluid. 293 00:21:58,680 --> 00:22:05,600 And was that specifically because that's where the isolates that were submitted or just with 294 00:22:05,600 --> 00:22:07,880 correlation with the clinical presentations? 295 00:22:07,880 --> 00:22:08,880 Yeah. 296 00:22:08,880 --> 00:22:13,920 So in our case, we can only do the genome sequencing on organisms that we have actually 297 00:22:13,920 --> 00:22:16,760 isolated in culture and grown in a lab. 298 00:22:16,760 --> 00:22:20,800 And although we did have some cases with other, where the gonorrhea was in other sites, we 299 00:22:20,800 --> 00:22:23,720 had a lot more trouble growing it out of that site. 300 00:22:23,720 --> 00:22:29,400 So for example, we had some heart tissue that we knew was positive for gonorrhea using molecular 301 00:22:29,400 --> 00:22:34,360 tests, but we weren't able to actually grow the gonorrhea from that site. 302 00:22:34,360 --> 00:22:38,640 In at least one case, we had blood from that same individual and we could grow the gonorrhea 303 00:22:38,640 --> 00:22:39,640 from the blood. 304 00:22:39,640 --> 00:22:40,640 Yeah. 305 00:22:40,640 --> 00:22:41,640 It's quite interesting. 306 00:22:41,640 --> 00:22:42,640 You know, it's tricky. 307 00:22:42,640 --> 00:22:46,400 Gonorrhea is a tricky pathogen for sure. 308 00:22:46,400 --> 00:22:48,000 I prefer that. 309 00:22:48,000 --> 00:22:49,000 So. 310 00:22:49,000 --> 00:22:52,200 The only silver lining to a lot of these cases though, and again, this is something that 311 00:22:52,200 --> 00:22:57,440 was noted in the older literature, but also confirmed in our study is that these bugs 312 00:22:57,440 --> 00:23:00,600 are not particularly drug resistant. 313 00:23:00,600 --> 00:23:05,040 They can still all be treated using common course of antibiotics. 314 00:23:05,040 --> 00:23:09,560 The only catch is, as you might imagine, by the time, you know, gonorrhea is circulating 315 00:23:09,560 --> 00:23:14,640 in your blood or other organs, treatment is a lot longer. 316 00:23:14,640 --> 00:23:21,400 So it takes a week to four weeks to treat it rather than a single dose of a couple drugs. 317 00:23:21,400 --> 00:23:27,520 And so that's one reason why it's great if you could do regular screening for gonorrhea. 318 00:23:27,520 --> 00:23:32,760 And even if you're not thinking STI, if somebody is, you know, sexually active or is with new 319 00:23:32,760 --> 00:23:39,520 partners or might've been exposed to do a screen for whatever STIs are out there. 320 00:23:39,520 --> 00:23:45,800 Because that's the other trick about a lot of these organisms is infection is often asymptomatic. 321 00:23:45,800 --> 00:23:47,640 And that's why we've changed our terms. 322 00:23:47,640 --> 00:23:52,680 It's no longer sexually transmitted diseases, but sexually transmitted infections because 323 00:23:52,680 --> 00:23:55,720 you can be having the disease actually present. 324 00:23:55,720 --> 00:23:56,720 Yeah, exactly. 325 00:23:56,720 --> 00:24:02,520 No, I think you mentioned a really good point there in terms of, you know, clinical presentations 326 00:24:02,520 --> 00:24:08,200 because clinically a lot of times, you know, you're thinking about sexually transmitted 327 00:24:08,200 --> 00:24:13,440 diseases in patients, but then all the testing doesn't get done or, you know, clinical picture 328 00:24:13,440 --> 00:24:16,000 doesn't fit. 329 00:24:16,000 --> 00:24:22,080 And then you lose them to contact or follow up and all of that combined, they can present 330 00:24:22,080 --> 00:24:23,560 with like a disseminated infection. 331 00:24:23,560 --> 00:24:28,880 So I think for clinicians out there, you know, having your work and, you know, some of these 332 00:24:28,880 --> 00:24:35,720 findings being published, I think helps because people are then becoming more aware of a situation 333 00:24:35,720 --> 00:24:38,720 that can present like disseminated gonorrhea. 334 00:24:38,720 --> 00:24:44,560 And so really keeping in mind that that can be a presentation if somebody presents with 335 00:24:44,560 --> 00:24:49,680 a joint infection, because typically that's not the first thing people think about when 336 00:24:49,680 --> 00:24:50,960 they're thinking about STIs. 337 00:24:50,960 --> 00:24:54,480 So our work still leaves a whole lot of unanswered questions. 338 00:24:54,480 --> 00:25:00,120 We're still going through our genome data sets to figure out what other virulence factors 339 00:25:00,120 --> 00:25:01,720 are probably present in these organisms. 340 00:25:01,720 --> 00:25:06,400 And there's got to be some, but finding the right tests and methods to evaluate those 341 00:25:06,400 --> 00:25:07,760 is tricky. 342 00:25:07,760 --> 00:25:12,320 The other question too is that the strains we're seeing, they're not exclusive to disseminated 343 00:25:12,320 --> 00:25:13,320 infections. 344 00:25:13,320 --> 00:25:15,680 They're also out there circulating causing uncomplicated infections. 345 00:25:15,680 --> 00:25:20,480 And so there's a whole other avenue of study that we're just trying to wrap our heads around 346 00:25:20,480 --> 00:25:26,200 about, you know, maybe it's not exclusively something that's special that these disseminated 347 00:25:26,200 --> 00:25:27,200 strains have. 348 00:25:27,200 --> 00:25:31,720 It might be something that's absent from other strains that prevents them or limits them 349 00:25:31,720 --> 00:25:33,520 from causing disseminated infection. 350 00:25:33,520 --> 00:25:38,480 So there's a whole other set of questions out there. 351 00:25:38,480 --> 00:25:43,800 And one other one we're wondering about is does the route of infection matter? 352 00:25:43,800 --> 00:25:46,560 Is there something else going on there? 353 00:25:46,560 --> 00:25:52,560 And again, this is purely speculation, but we're almost wondering if oropharyngeal exposure 354 00:25:52,560 --> 00:25:58,920 or oral sex or something like that might predispose you to disseminated infections just because 355 00:25:58,920 --> 00:26:02,480 folks often won't get tested for pharyngeal infections. 356 00:26:02,480 --> 00:26:04,180 They may not be picked up. 357 00:26:04,180 --> 00:26:10,360 And there's also some fascinating work being done on the natural history of infections 358 00:26:10,360 --> 00:26:15,360 that suggests that throat infections will clear up on their own often within three or 359 00:26:15,360 --> 00:26:16,360 four months. 360 00:26:16,360 --> 00:26:19,840 They may be infected, never, never treated. 361 00:26:19,840 --> 00:26:24,320 And yet over the time that you have this infection and maybe just like a little bit of a sore 362 00:26:24,320 --> 00:26:30,080 throat, which has many, many causes, especially during winter respiratory season, it gives 363 00:26:30,080 --> 00:26:33,320 a chance for the organism to get into your bloodstream. 364 00:26:33,320 --> 00:26:40,080 But again, those studies are very, very difficult to set up and look at because of all the stigma 365 00:26:40,080 --> 00:26:46,000 around studying sex and sexually transmitted infections and just the logistics of separating 366 00:26:46,000 --> 00:26:50,280 people who may only engage in oral sex versus other forms. 367 00:26:50,280 --> 00:26:51,280 Right. 368 00:26:51,280 --> 00:26:52,280 That's fair. 369 00:26:52,280 --> 00:26:53,280 Yeah. 370 00:26:53,280 --> 00:26:57,840 So in terms of, I guess you answered a couple of these questions already, but why is Manitoba 371 00:26:57,840 --> 00:27:02,000 or why was it speculated specifically Manitoba seeing these? 372 00:27:02,000 --> 00:27:05,120 And I know you mentioned, you know, host factors. 373 00:27:05,120 --> 00:27:11,340 We talked about specific areas that we normally see more sexually transmitted infections. 374 00:27:11,340 --> 00:27:17,820 I think the Prairie province is to have higher incidences of that in Canada, as we've seen 375 00:27:17,820 --> 00:27:22,380 with our syphilis rates as well, even here locally in Saskatchewan. 376 00:27:22,380 --> 00:27:28,080 But is there another speculation as to, or in your literature search, because I definitely 377 00:27:28,080 --> 00:27:35,400 didn't review the literature in Desemonee-Gonorrhea to see what Saskatchewan or Alberta was seeing, 378 00:27:35,400 --> 00:27:42,000 is there mention of other provinces having an increase in Desemonee-Gonorrhea as well? 379 00:27:42,000 --> 00:27:48,160 So it's hard to say specifically for Desemonee-Gonorrhea in Canada because it is a subject that's understudied 380 00:27:48,160 --> 00:27:49,160 at this point. 381 00:27:49,160 --> 00:27:54,200 But we do know that in the US there's been publications from several states who are seeing 382 00:27:54,200 --> 00:27:56,400 similar trends. 383 00:27:56,400 --> 00:28:00,120 And again, we're not sure at this point if it has something to do with the change in 384 00:28:00,120 --> 00:28:08,160 the circulating strain or if it's just related to overall across the Western world, there's 385 00:28:08,160 --> 00:28:11,320 an increase in sexually transmitted infections. 386 00:28:11,320 --> 00:28:20,240 Again, I mean, it's been 40 years since the HIV scare and for the past 20 years, Canada's 387 00:28:20,240 --> 00:28:23,560 been seeing an increase in sexually transmitted infections of all kinds. 388 00:28:23,560 --> 00:28:27,920 So we might just have hit that critical threshold where everyone is seeing more of these or 389 00:28:27,920 --> 00:28:31,280 at least recognizing more of these infections. 390 00:28:31,280 --> 00:28:36,200 There's really not anything special about Manitoba except for the fact that, and this 391 00:28:36,200 --> 00:28:42,200 is also true for Saskatchewan, because we are smaller provinces, we're able to do more 392 00:28:42,200 --> 00:28:46,120 comprehensive surveillance for all infectious diseases. 393 00:28:46,120 --> 00:28:48,800 We have laboratory capacity to do the testing. 394 00:28:48,800 --> 00:28:53,280 And so, for example, the amount of gonorrhea and chlamydia testing we do in Manitoba works 395 00:28:53,280 --> 00:28:57,120 out to be about one sample for every 10 people. 396 00:28:57,120 --> 00:29:02,560 So if you're sampling, it's not exactly 10% of the population we're testing. 397 00:29:02,560 --> 00:29:08,840 If you're looking at a significant proportion of the population every year for a given disease, 398 00:29:08,840 --> 00:29:12,760 you're going to be able to find that and also have very, very good years of surveillance. 399 00:29:12,760 --> 00:29:17,000 So what are, in the grand scheme, relatively subtle differences? 400 00:29:17,000 --> 00:29:22,520 Plus, we've been interested to some extent in sexually transmitted diseases in Manitoba 401 00:29:22,520 --> 00:29:26,560 for a while just because we are concerned about the growing rates of everything. 402 00:29:26,560 --> 00:29:29,120 But again, this is not unique to us. 403 00:29:29,120 --> 00:29:34,440 That's been across North America and especially also in Alberta. 404 00:29:34,440 --> 00:29:39,880 They've been doing very good surveillance and reporting on increases in sexually transmitted 405 00:29:39,880 --> 00:29:40,880 infections. 406 00:29:40,880 --> 00:29:46,840 The other thing too is just the changing technology makes these studies more and more available. 407 00:29:46,840 --> 00:29:51,840 And in Manitoba, we're lucky enough to have the Federal National Microbiology Lab. 408 00:29:51,840 --> 00:29:55,840 And I should really say that none of the work we've done here would have been possible without 409 00:29:55,840 --> 00:30:00,760 their gonococcal and streptococcus unit. 410 00:30:00,760 --> 00:30:07,040 Irene Martin at the National Microbiology Lab has been working on this subject for, well, 411 00:30:07,040 --> 00:30:14,040 a very long time and has also had a long-standing interest in the typing of gonorrhea for surveillance 412 00:30:14,040 --> 00:30:15,040 purposes. 413 00:30:15,040 --> 00:30:21,380 And so that was one of the early clues was that we were seeing the same molecular type 414 00:30:21,380 --> 00:30:23,200 over and over and over again. 415 00:30:23,200 --> 00:30:27,920 And really what the genomics has allowed us to do is take a much deeper dive into not 416 00:30:27,920 --> 00:30:32,960 only the handful of targets that are used for routine typing of gonorrhea, but the entire 417 00:30:32,960 --> 00:30:40,280 genome and the entire contingent of virulent factors and other things that are in a gonorrhea 418 00:30:40,280 --> 00:30:41,280 genome. 419 00:30:41,280 --> 00:30:45,200 And so we continue to work with her group to dig deeper into this. 420 00:30:45,200 --> 00:30:50,240 The other thing we are also working with some of our clinical colleagues is to get a better 421 00:30:50,240 --> 00:30:53,120 sense of who our patient population is. 422 00:30:53,120 --> 00:31:00,680 There still might be something about the patients who are presenting with gonorrhea. 423 00:31:00,680 --> 00:31:03,840 And a lot of that work is really just starting. 424 00:31:03,840 --> 00:31:09,520 But we already know, anecdotally at least, that in a lot of cases, these folks did not 425 00:31:09,520 --> 00:31:10,520 have gonorrhea. 426 00:31:10,520 --> 00:31:12,520 They were not positive at the routine sites. 427 00:31:12,520 --> 00:31:13,720 They didn't have positive urine. 428 00:31:13,720 --> 00:31:16,440 They didn't have positive endocervical swabs. 429 00:31:16,440 --> 00:31:20,040 So really the joint infection was their first presentation. 430 00:31:20,040 --> 00:31:25,440 And that's why it's also good to raise awareness that if you're not a microbiologist or someone 431 00:31:25,440 --> 00:31:30,960 who specializes in infectious diseases and somebody who's in their 20s, otherwise healthy, 432 00:31:30,960 --> 00:31:36,360 doesn't really have risk factors for acute onset arthritis, think about doing a sexually 433 00:31:36,360 --> 00:31:38,240 transmitted infection screen. 434 00:31:38,240 --> 00:31:44,440 Or if you're going to draw some joint fluid for culture and routine testing, maybe say, 435 00:31:44,440 --> 00:31:48,360 hey, could you query gonorrhea on the test? 436 00:31:48,360 --> 00:31:51,320 There seems to be a lot more of it out there. 437 00:31:51,320 --> 00:31:55,580 In some of the publications from the US, they are clearly seeing overlap with disseminated 438 00:31:55,580 --> 00:32:01,600 gonorrhea and other kinds of sexually transmitted infections, especially syphilis or HIV that 439 00:32:01,600 --> 00:32:06,720 may be associated with injection drug use or riskier habits or behaviors. 440 00:32:06,720 --> 00:32:11,520 But again, in our disseminated gonorrhea population, we're not seeing that. 441 00:32:11,520 --> 00:32:15,640 These are folks who don't seem to have other risk factors, which is also an indication 442 00:32:15,640 --> 00:32:18,160 that there may be something about the strain. 443 00:32:18,160 --> 00:32:22,280 They've just encountered a gonorrhea strain that is nastier than most, something that 444 00:32:22,280 --> 00:32:23,880 can happen to anyone. 445 00:32:23,880 --> 00:32:24,880 Yeah. 446 00:32:24,880 --> 00:32:30,120 And I think you bring a good point about the presentation of especially what I've seen 447 00:32:30,120 --> 00:32:34,240 from a joint that's infected with gonorrhea. 448 00:32:34,240 --> 00:32:42,000 It looks very similar to other bacterial septic arthritis, where it's hot, swollen, tender 449 00:32:42,000 --> 00:32:43,000 joints. 450 00:32:43,000 --> 00:32:49,360 Sometimes it can be overlooked that are most common bacteria like staph and strep species 451 00:32:49,360 --> 00:32:53,600 that would cause a septic arthritis being higher on the list. 452 00:32:53,600 --> 00:32:57,760 But then looking at the population, I think is really important. 453 00:32:57,760 --> 00:33:00,200 So I'm a pediatric infectious disease specialist. 454 00:33:00,200 --> 00:33:06,560 So for me in my world, sometimes until I don't see adolescent patients, that's when we start 455 00:33:06,560 --> 00:33:10,400 thinking more about STI screening and that type of thing. 456 00:33:10,400 --> 00:33:13,760 And obviously one-off cases in younger populations. 457 00:33:13,760 --> 00:33:21,360 But I think for some of our clinicians out there who are family physicians and practicing 458 00:33:21,360 --> 00:33:28,760 adult medicine really should be keeping in mind that gonorrhea can have such a presentation 459 00:33:28,760 --> 00:33:32,280 as well and sending off the right testing. 460 00:33:32,280 --> 00:33:36,840 So in terms of, I guess, what's the future? 461 00:33:36,840 --> 00:33:39,560 Can you predict the future for us, Dr. Alexander? 462 00:33:39,560 --> 00:33:41,240 What are we going to see? 463 00:33:41,240 --> 00:33:44,000 I will not even attempt to predict the future. 464 00:33:44,000 --> 00:33:48,680 But I guess now that this is on our radar, it's something that we will continue to monitor 465 00:33:48,680 --> 00:33:51,440 and continue to study. 466 00:33:51,440 --> 00:33:56,320 We'd like to better understand the mechanics of how all this works now that we have some 467 00:33:56,320 --> 00:34:00,680 targets from our genomic studies to go back to the lab bench and see if we can tease it 468 00:34:00,680 --> 00:34:04,560 a part a bit more and understand the mechanisms that work behind this. 469 00:34:04,560 --> 00:34:10,400 And as I mentioned, we're also very curious about taking a closer look at who gets disseminated 470 00:34:10,400 --> 00:34:11,400 gonorrhea. 471 00:34:11,400 --> 00:34:17,440 I mean, there are complement disorders in individuals that may predispose in these sorts 472 00:34:17,440 --> 00:34:18,440 of infections. 473 00:34:18,440 --> 00:34:23,760 And so that might be something that one might need to screen for if you present with disseminated 474 00:34:23,760 --> 00:34:24,760 gonorrhea. 475 00:34:24,760 --> 00:34:28,480 Well, maybe we should look at this because if you have an immune defect, there might 476 00:34:28,480 --> 00:34:33,760 be other implications for your own health and well-being and precautions you might take 477 00:34:33,760 --> 00:34:34,760 in the future. 478 00:34:34,760 --> 00:34:35,760 Yeah. 479 00:34:35,760 --> 00:34:42,680 And I think for some of our audience who are very clinical, that's like clinicians that 480 00:34:42,680 --> 00:34:50,880 are seeing this, you did mention that resistance was not a factor seen in your guys' isolates. 481 00:34:50,880 --> 00:34:57,360 Do we... so obviously anticipating that in the future, at this time right now, we're 482 00:34:57,360 --> 00:35:04,140 seeing our conventional antibiotics, which usually the cephalosporins is our mainstay 483 00:35:04,140 --> 00:35:06,880 of therapy still for gonococcal infections. 484 00:35:06,880 --> 00:35:07,880 Exactly. 485 00:35:07,880 --> 00:35:16,000 And so kind of going forward, is that something that you guys will keep kind of surveillance 486 00:35:16,000 --> 00:35:22,440 on for future isolates in terms of like developing, if there is a chance for resistance development? 487 00:35:22,440 --> 00:35:23,440 Yeah. 488 00:35:23,440 --> 00:35:28,160 I think one thing that most Canadian provincial public health labs do is if they have an isolate, 489 00:35:28,160 --> 00:35:30,280 they will do susceptibility testing. 490 00:35:30,280 --> 00:35:36,160 And again, the Public Health Agency of Canada does annual reports to describe changing trends 491 00:35:36,160 --> 00:35:41,080 in antibiotic resistance for gonorrhea as well as other organisms, because it's definitely 492 00:35:41,080 --> 00:35:43,880 something we need to monitor. 493 00:35:43,880 --> 00:35:47,720 And we know there are some nasty drug resistant strains out there. 494 00:35:47,720 --> 00:35:48,720 Yeah. 495 00:35:48,720 --> 00:35:51,460 And I think you did mention this in terms of diagnostics. 496 00:35:51,460 --> 00:35:58,440 So at this time, so I mean, based off of your study, you guys were able to do PCR and molecular 497 00:35:58,440 --> 00:36:01,160 methods from other sites, right? 498 00:36:01,160 --> 00:36:03,760 Like synovial fluid and your other isolates. 499 00:36:03,760 --> 00:36:09,920 So is that something that is available for North Americans or Canadians? 500 00:36:09,920 --> 00:36:10,920 So there are... 501 00:36:10,920 --> 00:36:16,600 So that's the other thing is there are no Health Canada approved diagnostic tests for 502 00:36:16,600 --> 00:36:22,880 disseminated gonorrhea infections, but we have a lot of really good laboratorians in 503 00:36:22,880 --> 00:36:29,920 Canada and they have the ability to validate these tests on their own and to offer them 504 00:36:29,920 --> 00:36:31,520 where required. 505 00:36:31,520 --> 00:36:39,240 Similarly, again, in part due to genomics and other advances in molecular techniques, 506 00:36:39,240 --> 00:36:45,280 we're looking at ways to generate an antimicrobial susceptibility profile or at least identify 507 00:36:45,280 --> 00:36:51,120 resistant genes even in the absence of having a clinical isolate to work with. 508 00:36:51,120 --> 00:36:52,480 But a lot of that is still very... 509 00:36:52,480 --> 00:36:55,720 It's a research and development stage and not wildly velo. 510 00:36:55,720 --> 00:37:00,880 But it's something that a lot of microbiology groups are moving towards is to being able 511 00:37:00,880 --> 00:37:04,400 to detect resistance without actually having an isolate. 512 00:37:04,400 --> 00:37:09,200 So as long as you have a positive sample, you can do that extra work to type strains 513 00:37:09,200 --> 00:37:14,160 for surveillance, to look at antimicrobial susceptibility, to help inform treatments 514 00:37:14,160 --> 00:37:18,560 and really to provide the best care you can even in the absence of a... 515 00:37:18,560 --> 00:37:23,040 Because now there's a lot of bugs out there that we still can't grow. 516 00:37:23,040 --> 00:37:26,240 You can't culture syphilis, for example. 517 00:37:26,240 --> 00:37:33,800 And even Brelia for Lyme disease, a lot of those diagnosis, you rarely, rarely isolate 518 00:37:33,800 --> 00:37:34,800 the organism itself. 519 00:37:34,800 --> 00:37:37,800 You have to go off of others. 520 00:37:37,800 --> 00:37:38,800 That's fair. 521 00:37:38,800 --> 00:37:39,800 Yeah. 522 00:37:39,800 --> 00:37:45,640 One of the points that I got from this great conversation today about disseminating gonorrhea 523 00:37:45,640 --> 00:37:52,080 is that obviously we should be aware that DGI, disseminated gonococcal infections are 524 00:37:52,080 --> 00:37:58,880 on the rise, that we should, especially as clinicians, be identifying cases, probably 525 00:37:58,880 --> 00:38:05,800 speaking with our local microbiologists and our laboratory staff members to kind of make 526 00:38:05,800 --> 00:38:09,920 them aware that we're suspicious that this could be a case of that. 527 00:38:09,920 --> 00:38:16,120 And if whether we could validate some of the molecular methods for certain samples and 528 00:38:16,120 --> 00:38:22,640 then also attempt to grow in culture, I think that would be ideal. 529 00:38:22,640 --> 00:38:27,600 But definitely, I think just keeping it on our radar that it doesn't have to present 530 00:38:27,600 --> 00:38:34,280 only as a common site for sexually transmitted infections or symptoms don't have to be quite 531 00:38:34,280 --> 00:38:35,280 classic. 532 00:38:35,280 --> 00:38:40,680 That they can present with joint infections and other areas for sure. 533 00:38:40,680 --> 00:38:44,200 And that we should be testing for it. 534 00:38:44,200 --> 00:38:45,680 We should be looking for it. 535 00:38:45,680 --> 00:38:51,640 And we should obviously, from a clinical standpoint, treatment varies too then, right? 536 00:38:51,640 --> 00:38:54,400 Like we talked about duration is longer. 537 00:38:54,400 --> 00:38:56,960 We are thinking about disseminated infections. 538 00:38:56,960 --> 00:39:02,880 So is there any other points that you would like to highlight for our audience today in 539 00:39:02,880 --> 00:39:06,400 terms of disseminated gonococcal infections? 540 00:39:06,400 --> 00:39:07,400 Not really. 541 00:39:07,400 --> 00:39:09,160 It's just great to have a chance to get the word out there. 542 00:39:09,160 --> 00:39:14,360 And yeah, there are clear guidelines and recommendations for diagnosis and treatment of disseminated 543 00:39:14,360 --> 00:39:15,600 infection. 544 00:39:15,600 --> 00:39:20,640 Where possible, if you can work with your local infectious disease docs and provincial 545 00:39:20,640 --> 00:39:25,040 public health labs to grow or investigate these cases, I think just documenting that 546 00:39:25,040 --> 00:39:30,600 they're out there and that they're not as rare as one would think is a great first step. 547 00:39:30,600 --> 00:39:34,720 Yeah, and it's exciting that we have such a great team out in Manitoba and with the 548 00:39:34,720 --> 00:39:41,200 National Micro Lab as well to be able to identify some of these cases, do future research. 549 00:39:41,200 --> 00:39:51,120 I think it's actually great to have such a center that can actually has the resources 550 00:39:51,120 --> 00:39:56,600 and the ability to probably even, I mean, helps all the rest of us in Canada as well. 551 00:39:56,600 --> 00:39:58,600 So we're quite grateful for that as well. 552 00:39:58,600 --> 00:39:59,600 So thank you. 553 00:39:59,600 --> 00:40:04,280 The thing I like about Manitoba is we're small but mighty. 554 00:40:04,280 --> 00:40:05,280 Well said. 555 00:40:05,280 --> 00:40:06,280 That's great. 556 00:40:06,280 --> 00:40:10,560 Well, thank you so much, Dr. Alexander for coming on today's episode. 557 00:40:10,560 --> 00:40:13,600 I think our audience is quite grateful. 558 00:40:13,600 --> 00:40:19,720 I've had a lot of requests actually for this episode because there are adult physicians, 559 00:40:19,720 --> 00:40:23,960 especially my adult colleagues that are seeing disseminated gonococcal infections. 560 00:40:23,960 --> 00:40:31,400 So I think just to hear a little bit about what research is ongoing and things to look 561 00:40:31,400 --> 00:40:39,080 for, I think definitely it's always refreshing to have somebody who's doing the actual work 562 00:40:39,080 --> 00:40:43,400 in the labs to come and give us that insight. 563 00:40:43,400 --> 00:40:44,400 So we're really appreciative. 564 00:40:44,400 --> 00:40:45,400 Thanks for the chance. 565 00:40:45,400 --> 00:40:46,400 All right. 566 00:40:46,400 --> 00:40:51,000 Well, take care and thank you so much for coming on the episode. 567 00:40:51,000 --> 00:40:55,000 Thank you, Dr. Purewall and thank you, Dr. Alexander for joining us. 568 00:40:55,000 --> 00:40:59,760 This concludes our first season of the Canadian Breakpoint and thank you listeners for making 569 00:40:59,760 --> 00:41:00,760 it a success. 570 00:41:00,760 --> 00:41:05,080 We look forward to bringing you exciting new topics in 2023. 571 00:41:05,080 --> 00:41:06,640 Have a topic suggestion? 572 00:41:06,640 --> 00:41:13,120 Email us at thecanadianbreakpoint at gmail.com and follow us on Twitter at CABbreakpoint. 573 00:41:13,120 --> 00:41:21,560 Have the happiest of holidays and see you in 2023 at the Canadian Breakpoint.