1 00:00:00,000 --> 00:00:12,880 Thanks for joining us at the Canadian Breakpoint, a Canadian infectious diseases podcast by 2 00:00:12,880 --> 00:00:15,680 Canadian infectious diseases physicians. 3 00:00:15,680 --> 00:00:20,760 I'm Summer Stewart, back with Dr. Rupeena Purewal, pediatric infectious diseases physician 4 00:00:20,760 --> 00:00:21,760 in Saskatoon. 5 00:00:21,760 --> 00:00:28,040 For this episode, we welcome Dr. Jason Kindrachuk from University of Manitoba to discuss monkey 6 00:00:28,040 --> 00:00:29,040 pox. 7 00:00:29,040 --> 00:00:30,040 Dr. Purewal. 8 00:00:30,040 --> 00:00:34,480 All right, welcome everyone to another episode of our podcast, the Canadian Breakpoint. 9 00:00:34,480 --> 00:00:40,120 Today we have a very special guest with us, Dr. Kindrachuk, who is an associate professor 10 00:00:40,120 --> 00:00:44,600 and Canada research chair in emerging virus pathogenesis in the Department of Medical 11 00:00:44,600 --> 00:00:49,800 Microbiology and Infectious Diseases and cross appointed in the Department of Internal Medicine 12 00:00:49,800 --> 00:00:56,080 and Manitoba Centre for Proteomics and Systems Biology, the University of Manitoba. 13 00:00:56,080 --> 00:01:01,800 His work focuses on viruses that pose the greatest threat to global health, including Ebola virus, 14 00:01:01,800 --> 00:01:06,880 orthophox viruses, coronaviruses and influenza viruses. 15 00:01:06,880 --> 00:01:12,000 His research program centers on the circulation, transmission and pathogenesis of emerging 16 00:01:12,000 --> 00:01:13,000 viruses. 17 00:01:13,000 --> 00:01:18,200 Past and present findings from these investigations will help inform emerging virus therapeutic 18 00:01:18,200 --> 00:01:23,360 treatment strategies, outbreak prediction and preparedness efforts with impacts on both 19 00:01:23,360 --> 00:01:25,040 human and animal health. 20 00:01:25,040 --> 00:01:31,120 Dr. Kinderchuck leads multiple nationally funded emerging infectious disease research 21 00:01:31,120 --> 00:01:37,360 investigations, including one health emerging zoonotic virus surveillance activities in 22 00:01:37,360 --> 00:01:38,880 Canada and Africa. 23 00:01:38,880 --> 00:01:46,080 These include as a director for the International M-Pox Response Consortium, co-lead for pillar 24 00:01:46,080 --> 00:01:51,040 two of the coronavirus variants rapid response network and ongoing investigations on the 25 00:01:51,040 --> 00:01:57,200 long-term impacts of Ebola virus infection in disease survivors in West Africa. 26 00:01:57,200 --> 00:02:00,040 Thank you so much, Dr. Kinderchuck for joining us today. 27 00:02:00,040 --> 00:02:01,040 Thank you for having me. 28 00:02:01,040 --> 00:02:02,040 Perfect. 29 00:02:02,040 --> 00:02:08,720 And so today we're going to talk about a very important topic and that's monkeypox for our 30 00:02:08,720 --> 00:02:09,800 listeners out there. 31 00:02:09,800 --> 00:02:16,840 So just so you're aware, there's pharmacists, physicians, nurses and many, many different 32 00:02:16,840 --> 00:02:20,240 other healthcare professionals that tune into the podcast. 33 00:02:20,240 --> 00:02:24,760 And so I thought monkeypox was, you know, it's an episode I've been wanting to do for 34 00:02:24,760 --> 00:02:25,760 a while. 35 00:02:25,760 --> 00:02:33,120 And I think with, you know, the recent WHO global health emergency that was reported 36 00:02:33,120 --> 00:02:39,400 just this past week, I think this is a pressing topic and all a lot of us are interested in 37 00:02:39,400 --> 00:02:41,440 kind of hearing more about this. 38 00:02:41,440 --> 00:02:42,440 Absolutely. 39 00:02:42,440 --> 00:02:43,440 All right. 40 00:02:43,440 --> 00:02:47,600 So I think for, because we have so many different types of listeners, I think it would be really 41 00:02:47,600 --> 00:02:52,480 important to kind of just start with a background and really what is this viral disease and 42 00:02:52,480 --> 00:02:54,320 you know, what is monkeypox? 43 00:02:54,320 --> 00:02:58,480 How does someone get this virus and what should we think about and when should we be thinking 44 00:02:58,480 --> 00:02:59,480 about it? 45 00:02:59,480 --> 00:03:01,360 Yeah, it's a great question, right? 46 00:03:01,360 --> 00:03:05,560 And I think for this kind of have to go back a little bit to, you know, when monkeypox 47 00:03:05,560 --> 00:03:11,080 virus was first identified, it was actually first identified in 1958 actually at really 48 00:03:11,080 --> 00:03:13,040 amongst captive non-human primates. 49 00:03:13,040 --> 00:03:16,160 We didn't see any human infections diagnosed until 1970. 50 00:03:16,160 --> 00:03:18,560 That was in democratic Republic of the Congo. 51 00:03:18,560 --> 00:03:22,840 But if we think about this from a historic perspective, that's probably not that surprising 52 00:03:22,840 --> 00:03:27,280 because there was this kind of other little thing going on in the world called smallpox 53 00:03:27,280 --> 00:03:31,080 that unfortunately had a very, very similar clinical presentation. 54 00:03:31,080 --> 00:03:36,960 So following the eradication of smallpox and obviously the cessation of the global vaccination 55 00:03:36,960 --> 00:03:43,080 program, what we've seen really from 1980 onwards, it's kind of steady increase in monkeypox 56 00:03:43,080 --> 00:03:46,520 virus infections across endemic regions of Africa. 57 00:03:46,520 --> 00:03:49,920 That's kind of been divided based on geography. 58 00:03:49,920 --> 00:03:51,920 Cameroon is the central point. 59 00:03:51,920 --> 00:03:57,740 Cameroon is the only place where we find both clade one and clade two monkeypox virus co-circulating. 60 00:03:57,740 --> 00:04:04,440 Anywhere west of Cameroon, we only find clade two monkeypox virus being endemic. 61 00:04:04,440 --> 00:04:08,480 And to the east of there is clade one monkeypox virus. 62 00:04:08,480 --> 00:04:13,560 Things get a little bit complicated when we start talking about how they differ from one 63 00:04:13,560 --> 00:04:14,560 another. 64 00:04:14,560 --> 00:04:18,560 Historically, clade one monkeypox virus has been associated with more severe disease, 65 00:04:18,560 --> 00:04:24,520 but we have to appreciate that that's also based on really kind of limited data for clade 66 00:04:24,520 --> 00:04:31,200 two infections really up until the reemergence in Nigeria in 2017 and then the subsequent 67 00:04:31,200 --> 00:04:37,720 movements out of Nigeria to the global north in 2022 and the obvious epidemic expansion. 68 00:04:37,720 --> 00:04:44,720 So historically, when we look at the disease, pre-2022, the disease looked really like a 69 00:04:44,720 --> 00:04:47,720 composite of human smallpox. 70 00:04:47,720 --> 00:04:52,580 Really the difference being the lymphadenopathy that's seen in monkeypox virus infections, 71 00:04:52,580 --> 00:04:58,340 but you still saw the fully disseminated disease, really the face, arms, legs, hands, and feet 72 00:04:58,340 --> 00:05:01,320 being the areas where you saw the most lesions. 73 00:05:01,320 --> 00:05:04,120 And the lesions tended to be all in the same stage of development. 74 00:05:04,120 --> 00:05:09,840 So whether it was on the face or on the feet, everything seemed to be fairly symmetrical 75 00:05:09,840 --> 00:05:11,380 in that regard. 76 00:05:11,380 --> 00:05:16,700 Then 2022 hits and we start seeing atypical presentation. 77 00:05:16,700 --> 00:05:24,340 So what we saw in 2022, virus moved out into Europe first and then moved globally across 78 00:05:24,340 --> 00:05:26,500 more than a hundred countries. 79 00:05:26,500 --> 00:05:29,400 Those infections were associated with dense sexual networks. 80 00:05:29,400 --> 00:05:32,660 That was something we hadn't really seen previously. 81 00:05:32,660 --> 00:05:37,400 Then there was this high overrepresentation amongst men and those that identify as gay, 82 00:05:37,400 --> 00:05:39,860 bisexual, or other men who have sex with men. 83 00:05:39,860 --> 00:05:45,840 The presentation tended to actually look a lot like other sexually transmitted or bloodborne 84 00:05:45,840 --> 00:05:46,840 infections. 85 00:05:46,840 --> 00:05:52,100 So a lot of lesions within the groin, some of the rectal lesions in men, isolated lesions 86 00:05:52,100 --> 00:05:57,600 in other regions of the body, but not the fully disseminated disease that we typically 87 00:05:57,600 --> 00:06:04,160 had seen historically and the lesions were not all in the same stage of development. 88 00:06:04,160 --> 00:06:10,120 That has complicated the picture because now you can't just do a clinical diagnosis based 89 00:06:10,120 --> 00:06:12,680 on what the disease looks like. 90 00:06:12,680 --> 00:06:16,520 So we still have virus moving through the global community. 91 00:06:16,520 --> 00:06:19,120 Clay 2b, monkeypox virus, continues to circulate. 92 00:06:19,120 --> 00:06:23,240 We've seen clusters in Canada since 2022 onwards. 93 00:06:23,240 --> 00:06:33,360 But then we saw the tipping point in DRC starting in 2023 with this massive increase in infections. 94 00:06:33,360 --> 00:06:39,880 And that's led to where we are today with the public health emergency. 95 00:06:39,880 --> 00:06:45,680 In terms of the signs and symptoms that people are seeing, is this widespread depending on 96 00:06:45,680 --> 00:06:48,680 the age group? 97 00:06:48,680 --> 00:06:54,080 Or younger children are seeing similar presentation as the adults? 98 00:06:54,080 --> 00:06:58,640 So far it really depends on the different clades. 99 00:06:58,640 --> 00:07:06,840 We almost have to take clade 2 and separate pre-2022 and almost pre-2017 versus post Nigeria 100 00:07:06,840 --> 00:07:09,680 reemergence and global reemergence. 101 00:07:09,680 --> 00:07:13,520 Prior to 2017, very few cases of clade 2 had ever been reported. 102 00:07:13,520 --> 00:07:17,000 We saw a small outbreak in the US in 2003. 103 00:07:17,000 --> 00:07:18,000 Some kids were infected. 104 00:07:18,000 --> 00:07:20,280 That was all through zoonotic transmission. 105 00:07:20,280 --> 00:07:22,920 We did see a couple of cases of severe disease there. 106 00:07:22,920 --> 00:07:26,840 But predominantly we didn't see a lot of fatal infections. 107 00:07:26,840 --> 00:07:31,760 2017, Nigeria, everything starts to skew a little bit older in terms of the average age 108 00:07:31,760 --> 00:07:34,080 group where we're seeing the infections. 109 00:07:34,080 --> 00:07:40,320 And then of course in 2022 onwards with the global outbreak, most infections in the 20 110 00:07:40,320 --> 00:07:46,600 to 40 age group in a game skewing towards men, very few infections in women and in kids. 111 00:07:46,600 --> 00:07:50,200 In DRC, very, very different. 112 00:07:50,200 --> 00:07:57,240 What we're seeing right now in really the last 20 months, even with this rapid increase 113 00:07:57,240 --> 00:08:05,560 in cases, the demographics for severe disease and infections have not really changed. 114 00:08:05,560 --> 00:08:11,120 In DRC, vast majority of infections still are based off of zoonotic contacts, mostly 115 00:08:11,120 --> 00:08:14,680 we think contact with rodents. 116 00:08:14,680 --> 00:08:18,680 Those infections tend to skew towards children under the age of 15. 117 00:08:18,680 --> 00:08:22,800 That tends to be the group that is in contact with those animals. 118 00:08:22,800 --> 00:08:28,480 And we tend to see the highest mortality and morbidity amongst those age groups. 119 00:08:28,480 --> 00:08:35,120 Now we also shift a little bit because mid 2023 we picked up, and I say weeks, it includes 120 00:08:35,120 --> 00:08:41,580 certainly at the forefront of this are Congolese colleagues and others from the US and Europe. 121 00:08:41,580 --> 00:08:48,800 We picked up a cluster of cases that were related to sexual contact in Congolese province. 122 00:08:48,800 --> 00:08:53,000 An N of five, very small, still skewing towards an older age group. 123 00:08:53,000 --> 00:08:55,420 But we saw men and women included in that. 124 00:08:55,420 --> 00:09:03,040 Since that time point, really in Selkivu province, we've seen again this massive inflection of 125 00:09:03,040 --> 00:09:07,160 cases in an area that historically had not seen much. 126 00:09:07,160 --> 00:09:13,520 Those cases over highly overrepresented among sex workers and dense sexual networks, but 127 00:09:13,520 --> 00:09:17,640 even seemingly evenly spread between men and women so far. 128 00:09:17,640 --> 00:09:22,240 We're not seeing much in terms of infections in kids, but that may change over time. 129 00:09:22,240 --> 00:09:27,480 We've seen movement of that particular type of monkeypox virus. 130 00:09:27,480 --> 00:09:31,980 What we've now termed clade 1B, more sustained human transmission. 131 00:09:31,980 --> 00:09:36,400 That virus has moved in a North Kivu and we've seen cases in internal displacement camps 132 00:09:36,400 --> 00:09:41,440 and that's included in, at least in our case investigations, in a few children. 133 00:09:41,440 --> 00:09:46,880 No severe disease so far, but we're still at the early stages. 134 00:09:46,880 --> 00:09:48,480 It's complicated. 135 00:09:48,480 --> 00:09:51,520 We're trying to follow the FD as closely as we can. 136 00:09:51,520 --> 00:09:57,840 Definitely different routes of transmission and that's been evolving as well. 137 00:09:57,840 --> 00:10:00,920 Has it been different for hosts, like host dependent as well? 138 00:10:00,920 --> 00:10:05,280 If somebody is immunocompromised, do they have more severe disease or they pick up the 139 00:10:05,280 --> 00:10:07,520 virus quicker? 140 00:10:07,520 --> 00:10:14,640 What we saw again in 2022 really opened our eyes a little bit to what monkeypox virus 141 00:10:14,640 --> 00:10:16,440 infections could look like. 142 00:10:16,440 --> 00:10:21,700 In 2022, there's a few global case series that looked at the risks for infection. 143 00:10:21,700 --> 00:10:27,280 There was an increased risk if somebody was HIV positive or a person living with HIV. 144 00:10:27,280 --> 00:10:29,800 Same thing with other STIs. 145 00:10:29,800 --> 00:10:34,720 We didn't know much at that point as to whether or not there was an increased risk for severity 146 00:10:34,720 --> 00:10:35,720 of disease. 147 00:10:35,720 --> 00:10:42,200 We've now seen with HIV that certainly people that have uncontrolled HIV can have a more 148 00:10:42,200 --> 00:10:47,960 severe course of M-pox than what we see in individuals who have control disease or otherwise 149 00:10:47,960 --> 00:10:53,720 have a normal immune response. 150 00:10:53,720 --> 00:10:55,200 But it's complicated. 151 00:10:55,200 --> 00:10:57,200 In Congo, we don't know. 152 00:10:57,200 --> 00:10:59,320 It certainly is top of mind for us. 153 00:10:59,320 --> 00:11:01,400 There's not a lot of STI testing. 154 00:11:01,400 --> 00:11:05,240 HIV rates tend to be quite low in Congo. 155 00:11:05,240 --> 00:11:10,240 That maybe has helped us a little bit, but we're hoping to deploy STI testing certainly 156 00:11:10,240 --> 00:11:15,240 in the South Kivu and some of the surrounding areas over the next few months. 157 00:11:15,240 --> 00:11:21,120 Then you talked a little bit about the common strains that are currently circulating. 158 00:11:21,120 --> 00:11:24,560 What is the predominant strain right now that you're seeing? 159 00:11:24,560 --> 00:11:31,760 Since it's Democratic Republic of the Congo, clade 1 monkeypox virus is the only type of 160 00:11:31,760 --> 00:11:34,040 monkeypox virus we've seen there before. 161 00:11:34,040 --> 00:11:37,720 We've now subdivided that into clade 1A and clade 1B. 162 00:11:37,720 --> 00:11:42,600 Clade 1A is the virus that's associated with zoonotic infections. 163 00:11:42,600 --> 00:11:47,880 Those are still making up the vast majority of the cases we see in DRC at the moment. 164 00:11:47,880 --> 00:11:54,440 Clade 1B we're seeing certainly in South Kivu starting to pick up in a few other areas now. 165 00:11:54,440 --> 00:12:01,040 That is associated with more sustained human-to-human transmission with no real zoonotic link. 166 00:12:01,040 --> 00:12:04,560 We don't know a lot about clade 1B yet in terms of severity. 167 00:12:04,560 --> 00:12:09,520 A number of factors we have to consider there, but we do know that it's certainly moving 168 00:12:09,520 --> 00:12:11,480 between people far easier. 169 00:12:11,480 --> 00:12:19,320 We think still through close contact and potentially with contaminated surfaces and shared materials 170 00:12:19,320 --> 00:12:24,960 or bedding and clothing, especially if somebody has a lesional disease. 171 00:12:24,960 --> 00:12:31,080 We haven't seen much in terms of changes in terms of things like a big respiratory component 172 00:12:31,080 --> 00:12:32,640 that's being included. 173 00:12:32,640 --> 00:12:37,680 But zoonotic infections certainly far and away are still driving the current outbreak. 174 00:12:37,680 --> 00:12:44,080 And then in terms of obviously, I think everybody is worried when they see a case like this. 175 00:12:44,080 --> 00:12:49,160 And so I guess we can divide it up into things because we can talk about prevention separately. 176 00:12:49,160 --> 00:12:54,080 And then when you do see a case, what do you do in terms of therapeutic management? 177 00:12:54,080 --> 00:12:58,440 So can you talk a little bit about how we can prevent and what kind of strategies are 178 00:12:58,440 --> 00:12:59,440 out there right now? 179 00:12:59,440 --> 00:13:03,840 Yeah, you know, the infection prevention control piece is something certainly I've been involved 180 00:13:03,840 --> 00:13:07,480 in and many others have been involved in since 2022. 181 00:13:07,480 --> 00:13:11,920 One of the things that I think we appreciate very quickly is certainly that kind of risk 182 00:13:11,920 --> 00:13:13,800 for broader airborne transmission. 183 00:13:13,800 --> 00:13:16,680 We haven't seen any FD that's suggestive of that. 184 00:13:16,680 --> 00:13:20,280 But historically, we've been able to gain a lot of knowledge, certainly from endemic 185 00:13:20,280 --> 00:13:21,280 regions of Africa. 186 00:13:21,280 --> 00:13:27,960 So really, the greatest risk for transmission we still see is that close extended contact, 187 00:13:27,960 --> 00:13:31,640 primarily through those that are providing care, whether they're health care workers 188 00:13:31,640 --> 00:13:36,640 or family members, whether they're sharing a bed, whether they're sharing clothing or 189 00:13:36,640 --> 00:13:40,200 bedding that is not being laundered. 190 00:13:40,200 --> 00:13:46,240 And we've seen the potential for transmission through things like sponges or cleaning materials. 191 00:13:46,240 --> 00:13:53,200 We've been working with a few groups, providing some guidance on looking at different disinfectants 192 00:13:53,200 --> 00:13:56,920 that are being used kind of in different areas of the world. 193 00:13:56,920 --> 00:14:02,360 The kind of good news is the majority of what we would assume continues to be the case. 194 00:14:02,360 --> 00:14:04,600 Bleach tends to work really well. 195 00:14:04,600 --> 00:14:09,320 Most good, you know, kind of, you know, antiviral disinfectants work very well. 196 00:14:09,320 --> 00:14:11,040 Soap and water work very well. 197 00:14:11,040 --> 00:14:16,400 A big piece of this is trying to ensure that anybody that has lesional disease that thinks 198 00:14:16,400 --> 00:14:20,600 that they are in contact with or bedding or clothing are getting laundered and that the 199 00:14:20,600 --> 00:14:25,240 people that are, you know, basically in contact with those things, either they're also monitoring 200 00:14:25,240 --> 00:14:29,040 their symptoms and or also using personal protective equipment. 201 00:14:29,040 --> 00:14:30,040 Okay. 202 00:14:30,040 --> 00:14:31,040 Yeah. 203 00:14:31,040 --> 00:14:39,200 So very similar to other viral diseases, encourage hand washing and inner basic hygiene and laundering. 204 00:14:39,200 --> 00:14:40,200 Absolutely. 205 00:14:40,200 --> 00:14:45,520 And our concern, I think right now with DRC, I mean, there's a big focus on certainly the 206 00:14:45,520 --> 00:14:48,960 sustained human to human transmission piece for good reason. 207 00:14:48,960 --> 00:14:53,600 But there's also a big piece of this, which is, listen, we know where really kind of the 208 00:14:53,600 --> 00:14:57,480 root of many of these infections are, and it's that zoonotic contact. 209 00:14:57,480 --> 00:15:00,960 There's a big piece of this, which I think is still, you know, kind of embedded in this 210 00:15:00,960 --> 00:15:06,480 idea of community engagement and trying to understand where infection prevention control 211 00:15:06,480 --> 00:15:11,560 practices can be implemented within communities that's done in a respectful and transparent 212 00:15:11,560 --> 00:15:17,440 manner in a way that doesn't impede people's ability to still hunt or to still be able 213 00:15:17,440 --> 00:15:20,120 to consume while game. 214 00:15:20,120 --> 00:15:26,440 And then once you have somebody who has a condition like this, who's contracted the 215 00:15:26,440 --> 00:15:30,680 virus, they have symptoms and they have signs and you're considering, you know, thinking 216 00:15:30,680 --> 00:15:36,440 about first, I guess we talk about diagnostics because if I'm an ER physician or a hospital 217 00:15:36,440 --> 00:15:41,040 physician, oftentimes as an infectious disease specialist, we'll get phone calls to send 218 00:15:41,040 --> 00:15:42,040 off. 219 00:15:42,040 --> 00:15:44,960 So what I see a patient like this, what do I send off? 220 00:15:44,960 --> 00:15:45,960 Yeah. 221 00:15:45,960 --> 00:15:49,280 So the easiest thing really is still is lesional swabs. 222 00:15:49,280 --> 00:15:53,520 OP swabs tend to work fairly well as well. 223 00:15:53,520 --> 00:15:58,280 There have been some studies that have looked at kind of longitudinal viremia in patients. 224 00:15:58,280 --> 00:16:02,280 Those I think for the most part have suggested there's not a really strong viremic component, 225 00:16:02,280 --> 00:16:04,320 at least in the majority of cases. 226 00:16:04,320 --> 00:16:08,960 So I think we're still kind of focused on lesional swabs. 227 00:16:08,960 --> 00:16:14,760 PCR by far and away is the method that still continues to be tried and true. 228 00:16:14,760 --> 00:16:20,120 There's been some changes though, because as we've seen kind of the emergence of clade 229 00:16:20,120 --> 00:16:25,160 2b coming out as a subclade out of clade 2 and now clade 1b is a subclade of clade 230 00:16:25,160 --> 00:16:30,120 1, we've also had to look at primers and whether or not those primers are still picking 231 00:16:30,120 --> 00:16:34,880 up the virus that we assume that they're recognizing. 232 00:16:34,880 --> 00:16:41,000 So for clade 1b, one of the things that we have seen recently has been that the kind 233 00:16:41,000 --> 00:16:46,400 of traditional primers that would be used normally for clade 1 infections, there's actually 234 00:16:46,400 --> 00:16:52,000 a deletion in clade 1b and those primers could potentially give a false negative. 235 00:16:52,000 --> 00:16:57,320 Colleagues in Europe have already reported primer sets that appear to recognize clade 236 00:16:57,320 --> 00:16:59,040 1b very, very well. 237 00:16:59,040 --> 00:17:05,960 But we also know that kind of like the overall kind of orthpox virus kind of centric primers 238 00:17:05,960 --> 00:17:06,960 work very, very well. 239 00:17:06,960 --> 00:17:10,120 They just don't give you that clade distinction, right? 240 00:17:10,120 --> 00:17:11,120 So PCR still works. 241 00:17:11,120 --> 00:17:13,320 We do a lot of sequencing. 242 00:17:13,320 --> 00:17:17,800 There's certainly something to be said about looking for antigens to try and identify people 243 00:17:17,800 --> 00:17:20,080 who have been previously exposed. 244 00:17:20,080 --> 00:17:24,320 We have done quite a bit of serosurveillance in this realm. 245 00:17:24,320 --> 00:17:28,240 The difficulty is pox viruses have very close antigenic similarities. 246 00:17:28,240 --> 00:17:34,920 That's why we use vaccinia for eradicating smallpox and we use it now for the M pox vaccine. 247 00:17:34,920 --> 00:17:39,520 That cross-reactivity somewhat precludes our ability to go in and say, okay, have you been 248 00:17:39,520 --> 00:17:47,240 exposed to monkey pox virus or cow pox virus or some other unknown human orth pox virus? 249 00:17:47,240 --> 00:17:52,120 That being said, in many areas that are endemic, we have a pretty good idea of what's circulating. 250 00:17:52,120 --> 00:17:56,240 And certainly if there's an outbreak situation, you can start to distinguish. 251 00:17:56,240 --> 00:17:59,800 There's questions about if somebody has been vaccinated for smallpox, what does cross-reactivity 252 00:17:59,800 --> 00:18:01,360 look like? 253 00:18:01,360 --> 00:18:06,720 But really if we use 1980 as that tipping point for people that were or weren't vaccinated, 254 00:18:06,720 --> 00:18:10,040 you can start to surmise what's going on based on that. 255 00:18:10,040 --> 00:18:11,400 That's fair. 256 00:18:11,400 --> 00:18:17,840 And then most centers, do they have the PCR testing or is this sent to National Microlab 257 00:18:17,840 --> 00:18:18,840 in Canada? 258 00:18:18,840 --> 00:18:20,640 Well, it's a good question. 259 00:18:20,640 --> 00:18:27,280 So certainly for clade 2 right now, like Cepheid has there, the gene expert is certainly widely 260 00:18:27,280 --> 00:18:29,200 being used for clade 2. 261 00:18:29,200 --> 00:18:30,960 That I think continues to be the case. 262 00:18:30,960 --> 00:18:36,520 For clade 1b, there's certainly been some questions about how we're going to be able 263 00:18:36,520 --> 00:18:42,040 to test for this and really to try and distinguish clade 1b from clade 2b. 264 00:18:42,040 --> 00:18:46,960 Using orth pox virus centric primers, you're still able to pick it up and say, okay, yeah, 265 00:18:46,960 --> 00:18:48,160 it's PCR positive. 266 00:18:48,160 --> 00:18:52,280 It's monkey pox virus, but we don't know which clade. 267 00:18:52,280 --> 00:18:57,920 For clade 1b, the issue that we have is this is a fairly recent development for the identification 268 00:18:57,920 --> 00:18:59,920 in Congo. 269 00:18:59,920 --> 00:19:03,840 So there's a lot of people that have been asking about access to nucleic acid to be 270 00:19:03,840 --> 00:19:07,200 able to validate tests within their own laboratories. 271 00:19:07,200 --> 00:19:12,360 And that's not only in Canada, but certainly well beyond and in too many different places 272 00:19:12,360 --> 00:19:13,360 across the globe. 273 00:19:13,360 --> 00:19:14,360 That's going to be a big piece. 274 00:19:14,360 --> 00:19:20,960 I think is that validation part likely, we're always a little bit behind with sharing materials 275 00:19:20,960 --> 00:19:22,520 globally unfortunately. 276 00:19:22,520 --> 00:19:26,480 I think right now, given the public health emergencies, that's going to be a big piece. 277 00:19:26,480 --> 00:19:30,640 But the confidence comes out of that the primer sets that have been reported so far that have 278 00:19:30,640 --> 00:19:34,880 been in use through Congo and in other regions. 279 00:19:34,880 --> 00:19:40,680 And then in terms of treatment, so are there antivirals out there or this is mainly supportive 280 00:19:40,680 --> 00:19:41,680 management currently? 281 00:19:41,680 --> 00:19:45,840 No, there's so for clade 2 infections, T-pox worked very, very well. 282 00:19:45,840 --> 00:19:53,040 Ticaviromat, ST246, I kind of have gone through every iteration of the name at this point, 283 00:19:53,040 --> 00:19:54,040 worked very, very well. 284 00:19:54,040 --> 00:19:59,960 And certainly in the US and Canada, that was kind of the antiviral that people were moving 285 00:19:59,960 --> 00:20:04,520 towards to try and reduce the impact of these infections. 286 00:20:04,520 --> 00:20:08,280 There's been an issue though that's come up in Congo, which is a very recent clinical 287 00:20:08,280 --> 00:20:12,720 trial for Ticaviromat on the ground failed. 288 00:20:12,720 --> 00:20:14,880 It didn't show any added benefit. 289 00:20:14,880 --> 00:20:18,200 The reality though is that it's unfortunate. 290 00:20:18,200 --> 00:20:25,040 There's probably a number of reasons why that trial may have been limited in its potential 291 00:20:25,040 --> 00:20:26,720 to be able to be successful. 292 00:20:26,720 --> 00:20:31,920 But a big piece that came out of that was you reduce the overall mortality just with 293 00:20:31,920 --> 00:20:34,160 providing good supportive care. 294 00:20:34,160 --> 00:20:39,480 And I think to me, that's a really important piece of this, which is for countries that 295 00:20:39,480 --> 00:20:46,520 have been scrambling for T-pox, certainly in 2022, maybe looking to do that for 2024. 296 00:20:46,520 --> 00:20:51,320 Blade 1B, we don't think it works, but if you provide good supportive care, you reduce 297 00:20:51,320 --> 00:20:53,120 certainly the mortality. 298 00:20:53,120 --> 00:20:58,160 I think the bigger kind of piece of all that though is saying in the areas where we see 299 00:20:58,160 --> 00:21:02,760 endemic disease, one of the things that we can do to immediately reduce the impact is 300 00:21:02,760 --> 00:21:07,800 be able to provide extra assistance for being able to give supportive care on the ground. 301 00:21:07,800 --> 00:21:10,040 So I think that's an important piece. 302 00:21:10,040 --> 00:21:11,120 Vaccination still works well. 303 00:21:11,120 --> 00:21:16,800 We have no reason to think the MDA, the very Nordic vaccine would not provide cross protection 304 00:21:16,800 --> 00:21:18,360 against Blade 1. 305 00:21:18,360 --> 00:21:20,600 It's still a vaccine based vaccine. 306 00:21:20,600 --> 00:21:24,120 So I don't think we have any concerns that way. 307 00:21:24,120 --> 00:21:29,800 A big part is still trying to get vaccines to really the hotspots of the world where 308 00:21:29,800 --> 00:21:32,600 we see circulation and that continues to be an issue. 309 00:21:32,600 --> 00:21:38,760 And so, yeah, so I would say I've had a couple of questions from physicians and colleagues 310 00:21:38,760 --> 00:21:40,440 and patients. 311 00:21:40,440 --> 00:21:46,120 Is it worthwhile for them to get vaccinated or is it something only limited to if they're 312 00:21:46,120 --> 00:21:48,720 traveling to these endemic areas? 313 00:21:48,720 --> 00:21:55,400 Even through travel, I don't know if there's a travel based vaccination program that's 314 00:21:55,400 --> 00:21:56,400 available. 315 00:21:56,400 --> 00:22:00,240 That may change because of the public health emergency. 316 00:22:00,240 --> 00:22:06,000 My lab and myself have been vaccinated because we obviously work with samples as well as 317 00:22:06,000 --> 00:22:08,960 with vaccine of virus and other pox viruses. 318 00:22:08,960 --> 00:22:14,360 I was vaccinated ages ago for ACAM2000 or with ACAM2000. 319 00:22:14,360 --> 00:22:16,800 The public availability is still pretty limited, right? 320 00:22:16,800 --> 00:22:17,800 Yeah. 321 00:22:17,800 --> 00:22:22,320 We have lots of stocks and stockpiles of ACAM2000, but that was contraindicated for certainly 322 00:22:22,320 --> 00:22:24,360 for very specific groups. 323 00:22:24,360 --> 00:22:30,320 The JYNNEOS or MBA vaccine, we don't have nearly the stockpile that we did. 324 00:22:30,320 --> 00:22:34,840 So there's still basically the push to try and get that vaccine to those populations 325 00:22:34,840 --> 00:22:40,200 where there is an increased risk for infection, close contacts of patients that have suspected 326 00:22:40,200 --> 00:22:42,120 or confirmed cases. 327 00:22:42,120 --> 00:22:47,320 That's still the focus, but as well kind of appreciating that we need to get vaccine into 328 00:22:47,320 --> 00:22:52,440 certainly in the Congo and probably now into Burundi and surrounding areas very, very quickly. 329 00:22:52,440 --> 00:22:59,600 So I think if we start seeing influx in cases, whether clade two or clade one driven in Canada, 330 00:22:59,600 --> 00:23:04,040 there's going to be a need to ensure that healthcare workers are vaccinated. 331 00:23:04,040 --> 00:23:08,520 But there's the other piece too, which is good infection prevention control also is 332 00:23:08,520 --> 00:23:11,040 very, very good at reducing those infections. 333 00:23:11,040 --> 00:23:14,720 So we just have to kind of take it at face value. 334 00:23:14,720 --> 00:23:15,720 Right. 335 00:23:15,720 --> 00:23:16,720 Okay. 336 00:23:16,720 --> 00:23:19,600 And so kind of the idea being prevention right now. 337 00:23:19,600 --> 00:23:26,680 Even if somebody does have the illness to be cautious, to not be around others, especially 338 00:23:26,680 --> 00:23:30,280 those that are immune compromised, kind of similar to what we would say with any other 339 00:23:30,280 --> 00:23:31,280 viral infections. 340 00:23:31,280 --> 00:23:32,280 100%. 341 00:23:32,280 --> 00:23:33,280 Right. 342 00:23:33,280 --> 00:23:36,280 And we know the thing is we know that the routes transmission predominantly, right? 343 00:23:36,280 --> 00:23:40,360 You know, eucosal membranes are going to be key in ensuring that we don't have any open 344 00:23:40,360 --> 00:23:42,040 wounds or abrasions. 345 00:23:42,040 --> 00:23:43,520 Those kinds of things continue to be important. 346 00:23:43,520 --> 00:23:47,760 And I think we go back to the idea of when people are vaccinating people, certainly old 347 00:23:47,760 --> 00:23:51,920 school, like CAM 2000 or even way back in the flybacks, it was about those preventative 348 00:23:51,920 --> 00:23:54,720 measures trying to remove the risk for exposure. 349 00:23:54,720 --> 00:23:55,720 Right. 350 00:23:55,720 --> 00:24:01,080 And so recently with WHO declaring this public health and global health emergency. 351 00:24:01,080 --> 00:24:05,400 And so how is situation evolving and appreciating that things are changing daily? 352 00:24:05,400 --> 00:24:06,400 I'm sure. 353 00:24:06,400 --> 00:24:07,400 Yeah. 354 00:24:07,400 --> 00:24:11,920 I mean, the situation on the ground in Congo, you know, through certainly through the work 355 00:24:11,920 --> 00:24:15,800 that we're doing, I don't think that the situation has necessarily changed. 356 00:24:15,800 --> 00:24:21,120 We're looking at from 2023 and now around 30,000 suspected cases. 357 00:24:21,120 --> 00:24:28,200 We've seen movement of virus really to 25 to 26 provinces now with local transmission. 358 00:24:28,200 --> 00:24:29,440 It continues to be widespread. 359 00:24:29,440 --> 00:24:33,920 And we're not seeing any indication that things are starting to ramp down. 360 00:24:33,920 --> 00:24:34,920 Right. 361 00:24:34,920 --> 00:24:37,900 So that continues to be a big concern for us. 362 00:24:37,900 --> 00:24:43,880 Probably as concerning of an issue though, is really the movement into Burundi and some 363 00:24:43,880 --> 00:24:45,160 of the surrounding regions. 364 00:24:45,160 --> 00:24:50,960 Burundi in particular, because of the limited resources that are available in country from 365 00:24:50,960 --> 00:24:57,000 a healthcare standpoint and just an overall standpoint, concerns about the increased circulation 366 00:24:57,000 --> 00:24:58,600 that we're now seeing there. 367 00:24:58,600 --> 00:25:01,480 You know, Uganda and Rwanda, we've seen cases. 368 00:25:01,480 --> 00:25:03,720 Kenya, we've seen cases. 369 00:25:03,720 --> 00:25:06,600 Those seem to be pretty controlled so far. 370 00:25:06,600 --> 00:25:11,140 That's assuming that people are feeling comfortable with self-reporting. 371 00:25:11,140 --> 00:25:14,840 But I think for us that the focus right now is really what's going on in Congo, what's 372 00:25:14,840 --> 00:25:16,600 going on in Burundi. 373 00:25:16,600 --> 00:25:22,720 We've seen introduction or at least the kind of the indication of cases that have been 374 00:25:22,720 --> 00:25:23,720 identified globally. 375 00:25:23,720 --> 00:25:25,040 So we've seen a case in Sweden. 376 00:25:25,040 --> 00:25:27,840 We've now seen a case in Thailand. 377 00:25:27,840 --> 00:25:30,960 That's not that surprising, right? 378 00:25:30,960 --> 00:25:32,200 People are still traveling. 379 00:25:32,200 --> 00:25:37,480 People are still living in a globalized community. 380 00:25:37,480 --> 00:25:40,600 We're likely going to see those cases continue to be identified. 381 00:25:40,600 --> 00:25:43,960 The bigger piece to me is going to be what happens afterwards? 382 00:25:43,960 --> 00:25:50,160 Do you see any additional signs of community transmission or broader transmission within 383 00:25:50,160 --> 00:25:52,160 those local populations? 384 00:25:52,160 --> 00:25:57,600 Or did you get good testing and contact tracing out and you don't see any local spread? 385 00:25:57,600 --> 00:26:00,560 So that I think continues to be important for developments. 386 00:26:00,560 --> 00:26:06,400 The other piece is we've seen, you know, really the kind of discussion about getting vaccines 387 00:26:06,400 --> 00:26:11,680 on the ground in Congo go from being a few months down the road to now kind of like within 388 00:26:11,680 --> 00:26:14,440 the next couple of weeks there will be vaccine. 389 00:26:14,440 --> 00:26:17,680 Don't know much about the deployment strategy yet, what that's going to look like, which 390 00:26:17,680 --> 00:26:22,040 groups are going to be going to be kind of the focal groups for that first round. 391 00:26:22,040 --> 00:26:26,960 But certainly we're there and others are there to help support where we can and certainly 392 00:26:26,960 --> 00:26:33,120 to try to get some clinical information out as quick as possible where and when we can. 393 00:26:33,120 --> 00:26:34,120 Okay. 394 00:26:34,120 --> 00:26:38,560 Seems like a very pressing situation, but you know, things, I think there's things are 395 00:26:38,560 --> 00:26:44,360 in the works and hopefully, you know, we don't see more spread in circulating virus because 396 00:26:44,360 --> 00:26:50,440 obviously we know what with the previous kind of virus activities we've seen over the last 397 00:26:50,440 --> 00:26:53,560 few years, we know that things can change really quickly. 398 00:26:53,560 --> 00:26:59,080 So, and then, so in terms of Canada or other countries, what are they doing in terms of 399 00:26:59,080 --> 00:27:03,720 like mitigating risks or surveillance for disease surveillance? 400 00:27:03,720 --> 00:27:04,920 Yeah. 401 00:27:04,920 --> 00:27:09,340 You know, I think one of the big pieces that, you know, that has maybe not gone as much 402 00:27:09,340 --> 00:27:14,120 presses as it's needed to over the last bit is we have this pressing situation in Central 403 00:27:14,120 --> 00:27:15,120 Africa. 404 00:27:15,120 --> 00:27:18,760 There's been a bigger question about, okay, well, what happens now if clade one moves 405 00:27:18,760 --> 00:27:21,240 more broadly and especially clade one B. 406 00:27:21,240 --> 00:27:26,000 The thing that I think we need to appreciate is, you know, two years out from 2022 to appreciate 407 00:27:26,000 --> 00:27:31,160 that listen, our surveillance networks, our testing and tracing networks, the knowledge 408 00:27:31,160 --> 00:27:38,840 base in our healthcare workers and as well, even within communities and community advocacy 409 00:27:38,840 --> 00:27:43,560 groups, all of that has increased to a much higher level than it was pre-2022. 410 00:27:43,560 --> 00:27:46,900 So I think we're in a very good place for identifying cases. 411 00:27:46,900 --> 00:27:51,920 We continue to see, you know, cases being identified in Ontario, a little bit of a surge, 412 00:27:51,920 --> 00:27:53,940 you know, kind of coming through this summer. 413 00:27:53,940 --> 00:27:59,080 Same thing with other regions of the world, not approaching anything what we saw in 2022, 414 00:27:59,080 --> 00:28:02,960 but it should be a reminder that like clay to virus didn't disappear. 415 00:28:02,960 --> 00:28:04,940 It's still circulating globally. 416 00:28:04,940 --> 00:28:07,500 It's still circulating here within Canada. 417 00:28:07,500 --> 00:28:09,600 It's just at a very, very low level. 418 00:28:09,600 --> 00:28:13,960 So I think we're doing very, very good in terms of our surveillance. 419 00:28:13,960 --> 00:28:18,440 We now have to add the PCN about clay one B recognition, but we're in a place where 420 00:28:18,440 --> 00:28:22,200 we should be able to identify those, those cases very, very quickly. 421 00:28:22,200 --> 00:28:23,360 That's really good to hear. 422 00:28:23,360 --> 00:28:28,760 And so in terms of resources, cause I think that's also important for healthcare professionals 423 00:28:28,760 --> 00:28:33,120 across the board, also sometimes just general public, you know, asking questions. 424 00:28:33,120 --> 00:28:38,040 And so where can people find, I mean, like obviously CBC has always been a really good 425 00:28:38,040 --> 00:28:41,760 resource, but are there other certain areas that we should be looking? 426 00:28:41,760 --> 00:28:42,760 There, there are. 427 00:28:42,760 --> 00:28:46,560 I mean, I, you know, I don't want to, you've got to shine a spotlight on work that I've 428 00:28:46,560 --> 00:28:52,120 done because I've sat on panels with far smarter people to myself to pronounce on this. 429 00:28:52,120 --> 00:28:56,680 WHO a couple of years ago had a guideline development group for clinical management, 430 00:28:56,680 --> 00:28:58,480 infection prevention control. 431 00:28:58,480 --> 00:29:00,720 That's really available through, through WHO for M pox. 432 00:29:00,720 --> 00:29:05,480 I think that's still largely applies to everything that we're seeing now. 433 00:29:05,480 --> 00:29:10,240 WHO just recently updated all their information on infection prevention control, their descriptions 434 00:29:10,240 --> 00:29:12,560 of M pox, those resources are good. 435 00:29:12,560 --> 00:29:17,200 And of course health Canada and public health agency of Canada continue to provide information 436 00:29:17,200 --> 00:29:18,200 as well. 437 00:29:18,200 --> 00:29:21,360 And of course there's, there are research groups that are doing work in this area. 438 00:29:21,360 --> 00:29:25,920 You know, all of us have a lot of information as well, but I think going to those kind of 439 00:29:25,920 --> 00:29:31,880 big sources, European centers for disease control, U S T D C, WHO and, and health Canada 440 00:29:31,880 --> 00:29:34,440 are major resources. 441 00:29:34,440 --> 00:29:35,440 That's really helpful. 442 00:29:35,440 --> 00:29:39,680 Cause I think a lot of people will be starting to see more questions come through and that's 443 00:29:39,680 --> 00:29:42,560 kind of natural that happens clinically as well. 444 00:29:42,560 --> 00:29:47,160 You know, we always think about what's happening with circulating and I think awareness is 445 00:29:47,160 --> 00:29:48,160 important. 446 00:29:48,160 --> 00:29:52,480 And so that's why we're talking about this today, because I think most of us should have 447 00:29:52,480 --> 00:29:58,160 some base knowledge on monkey pox and, and you've given us some really good information 448 00:29:58,160 --> 00:29:59,160 today. 449 00:29:59,160 --> 00:30:05,360 So in terms of kind of summarizing or some key points that you'd want the public or health 450 00:30:05,360 --> 00:30:11,880 professionals to really take away from today's episode, what would you kind of summarize 451 00:30:11,880 --> 00:30:13,320 in terms of that? 452 00:30:13,320 --> 00:30:17,520 Yeah, I think a big piece of this is right now that the global risk for, for clade one 453 00:30:17,520 --> 00:30:19,640 introduction continues to be quite low. 454 00:30:19,640 --> 00:30:22,340 I think also appreciating that, you know, things can change. 455 00:30:22,340 --> 00:30:25,240 We know that that happened with clay too, but we're in a different place than we were 456 00:30:25,240 --> 00:30:26,780 in, in 2022. 457 00:30:26,780 --> 00:30:28,500 We have good surveillance networks. 458 00:30:28,500 --> 00:30:30,760 We have good sharing of data and testing protocols. 459 00:30:30,760 --> 00:30:34,000 I think that piece allowed us to be able to move forward. 460 00:30:34,000 --> 00:30:38,560 The kind of piece that I think is at the heart of this though, is we want to reduce the risk 461 00:30:38,560 --> 00:30:39,560 globally. 462 00:30:39,560 --> 00:30:44,440 We've got to reduce the risk locally, which still gets back to the need to not only get 463 00:30:44,440 --> 00:30:49,040 things contained in, in DRC, but also to look at other endemic areas of Africa and say, 464 00:30:49,040 --> 00:30:51,640 we need to get vaccination programs up. 465 00:30:51,640 --> 00:30:57,160 We need to get surveillance programs sustained and as well go back to this piece about healthcare 466 00:30:57,160 --> 00:31:02,200 infrastructure and certainly the need to be able to harmonize data reporting globally 467 00:31:02,200 --> 00:31:03,360 right now for M-POC. 468 00:31:03,360 --> 00:31:08,000 So we all have a good impression of what we're looking for, but I think it's going to be 469 00:31:08,000 --> 00:31:09,480 a key area. 470 00:31:09,480 --> 00:31:10,480 Yeah. 471 00:31:10,480 --> 00:31:16,640 And then just on a note that I actually forgot to ask was in terms of reporting. 472 00:31:16,640 --> 00:31:22,760 So if physicians or anybody is seeing cases, are these then like, I mean, through the lab, 473 00:31:22,760 --> 00:31:26,840 we're definitely reporting to public health, like local public health authorities. 474 00:31:26,840 --> 00:31:31,560 Is there something that a physician should be doing in terms of any surveillance network 475 00:31:31,560 --> 00:31:35,400 that they should be entering their data into? 476 00:31:35,400 --> 00:31:37,160 Not that I've seen so far, right? 477 00:31:37,160 --> 00:31:41,480 And listen, that can just be my naivety for what, what's available in Canada. 478 00:31:41,480 --> 00:31:46,480 In DRC, we've got, WHO has their centralized system for us to be able to report and upload 479 00:31:46,480 --> 00:31:48,280 data continually into. 480 00:31:48,280 --> 00:31:53,200 So we've, we've been working on that and certainly most, most of those countries have good centralized 481 00:31:53,200 --> 00:31:56,640 systems for entering in national data. 482 00:31:56,640 --> 00:32:00,720 It can be a little bit slow at times, but we continue to do that on the ground as well. 483 00:32:00,720 --> 00:32:06,420 And then of course, Africa CDC is obviously taking a much bigger role in this with trying 484 00:32:06,420 --> 00:32:11,520 to ensure that there's good data reporting, data management, and as well sharing of information 485 00:32:11,520 --> 00:32:12,520 globally. 486 00:32:12,520 --> 00:32:13,520 Okay. 487 00:32:13,520 --> 00:32:14,520 That's great. 488 00:32:14,520 --> 00:32:19,480 Definitely, I think everybody's on top of it and it's good to hear a little bit more, 489 00:32:19,480 --> 00:32:23,080 you know, about Monkeypox and, and have a bit more background. 490 00:32:23,080 --> 00:32:25,160 So I've learned a lot for sure. 491 00:32:25,160 --> 00:32:30,280 And, and I always inform my listeners that this is an informational podcast and things 492 00:32:30,280 --> 00:32:37,240 do evolve and, and over time, you know, even prevention or treatment options may change. 493 00:32:37,240 --> 00:32:41,760 So currently this is the situation with Monkeypox and, and what we know about it right now. 494 00:32:41,760 --> 00:32:47,480 So I'm sure our listeners will take a lot back from this episode and thank you Dr. 495 00:32:47,480 --> 00:32:53,720 Kindertruck for being here today on our podcast and providing us with such great information. 496 00:32:53,720 --> 00:32:55,280 It was an absolute pleasure. 497 00:32:55,280 --> 00:32:56,280 Thank you. 498 00:32:56,280 --> 00:32:57,280 Thanks. 499 00:32:57,280 --> 00:32:58,280 Take care. 500 00:32:58,280 --> 00:33:00,360 Thank you, Dr. Kindertruck for joining us today. 501 00:33:00,360 --> 00:33:01,840 Have an episode suggestion? 502 00:33:01,840 --> 00:33:08,240 Email the Canadian Breakpoint at gmail.com and be sure to follow us on X at CA Breakpoint 503 00:33:08,240 --> 00:33:09,240 for updates. 504 00:33:09,240 --> 00:33:14,360 See you again soon at the Canadian Breakpoint.