1 00:00:05,265 --> 00:00:06,105 Hi everyone. 2 00:00:06,165 --> 00:00:10,515 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:11,175 --> 00:00:14,985 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:14,985 --> 00:00:16,425 and antimicrobial management. 5 00:00:16,593 --> 00:00:19,853 I'm Sara Dong, your host and a Med-Peds ID doc. 6 00:00:19,960 --> 00:00:23,350 In today's episode, we're continuing to talk a little bit more about 7 00:00:23,350 --> 00:00:25,360 vaccine preventable illnesses. 8 00:00:25,588 --> 00:00:30,358 If you haven't already, check out our last episode with Dr. Adam Ratner. 9 00:00:30,584 --> 00:00:34,694 You can also check out episode number 102 called Rubeola Response. 10 00:00:35,050 --> 00:00:37,270 I will go ahead and introduce our guests today. 11 00:00:37,840 --> 00:00:41,620 First up, we have Dr. Sumanth Cherukumilli, who was previously on 12 00:00:41,620 --> 00:00:46,050 Febrile in episode number 95, which was live from Memphis and the St. 13 00:00:46,050 --> 00:00:48,780 Jude PIDS Pediatric ID conference. 14 00:00:49,230 --> 00:00:53,430 He is a 3rd year pediatric ID fellow at the University of Maryland. 15 00:00:53,560 --> 00:00:54,890 He works with Drs. 16 00:00:55,030 --> 00:01:01,534 Milli Tapia, Karen Kotloff, Samba Sow, and Adama Mamby Keita on childhood 17 00:01:01,534 --> 00:01:03,544 antimicrobial resistance in West Africa. 18 00:01:04,984 --> 00:01:09,904 He was the winner of the 2024 Pediatric ID Society, PIDS, Sanofi 19 00:01:09,904 --> 00:01:13,620 Pasteur Fellowship Award, which he used to launch a new neonatal sepsis 20 00:01:13,620 --> 00:01:17,310 study designed to study the impact of antibiotic choice on patient survival. 21 00:01:17,699 --> 00:01:19,029 Hi, I am Sumanth. 22 00:01:19,049 --> 00:01:22,049 I'm a third year Peds ID fellow at the University of Maryland. 23 00:01:22,619 --> 00:01:25,469 Thanks for having me on, Sara, it's good to see you again. 24 00:01:26,399 --> 00:01:29,129 He is joined by two of his mentors I just mentioned. 25 00:01:29,639 --> 00:01:34,709 Dr. Adama Mamby Keita is the head of the Department of Epidemiology 26 00:01:34,709 --> 00:01:38,119 at the Center for Vaccine Development Mali in Bamako Mali. 27 00:01:38,789 --> 00:01:42,689 He has spent over two decades conducting field research in Mali and has played 28 00:01:42,689 --> 00:01:47,219 critical roles in multiple surveillance studies, sero survey studies, and clinical 29 00:01:47,219 --> 00:01:49,289 trials from phase two to phase four. 30 00:01:49,436 --> 00:01:53,186 He has played a key role in data to action implementation in Mali and has 31 00:01:53,186 --> 00:01:56,846 been instrumental in saving the lives of many Malian children through his efforts. 32 00:01:57,260 --> 00:01:58,100 Hi everyone. 33 00:01:58,100 --> 00:01:59,745 My name is Adama Keita. 34 00:01:59,765 --> 00:02:04,005 I am, uh, a medical doctor from CVD-Mali working in clinical 35 00:02:04,365 --> 00:02:06,010 research, uh, to save lives. 36 00:02:06,250 --> 00:02:06,790 Thank you. 37 00:02:06,820 --> 00:02:07,720 Nice to meet you. 38 00:02:08,650 --> 00:02:12,010 And last we have Dr. Milagritos Tapia or Millie Tapia. 39 00:02:12,520 --> 00:02:15,790 She's a professor of pediatrics and a pediatric ID attending 40 00:02:15,880 --> 00:02:17,530 at the University of Maryland. 41 00:02:18,220 --> 00:02:22,660 She has served as PI or co-PI on multiple large vaccine based surveillance studies 42 00:02:22,840 --> 00:02:26,443 and clinical trials, and she has also played an extremely important role 43 00:02:26,448 --> 00:02:30,813 in introducing multiple vaccinations, including Hib, pneumococcal, and 44 00:02:30,813 --> 00:02:34,503 meningococcal vaccines in Mali, leading to a major decrease in the burden 45 00:02:34,503 --> 00:02:36,333 of vaccine preventable illnesses. 46 00:02:36,722 --> 00:02:37,922 Hi, I am Mili Tapia. 47 00:02:37,922 --> 00:02:41,002 I'm at the University of Maryland School of Medicine at the Center for 48 00:02:41,002 --> 00:02:42,772 Vaccine Development and Global Health. 49 00:02:42,802 --> 00:02:44,632 And, happy to be here. 50 00:02:44,692 --> 00:02:48,192 Uh, nice to meet you and look forward to a great conversation. 51 00:02:49,372 --> 00:02:52,612 So Febrile is everyone's favorite cultured podcast. 52 00:02:52,612 --> 00:02:55,912 So we ask our guests to share a little piece of culture, just 53 00:02:55,912 --> 00:02:59,452 something that makes you happy or that you've enjoyed recently. 54 00:03:00,852 --> 00:03:03,742 I really like reading, and I like writing. 55 00:03:03,982 --> 00:03:07,432 Um, so my favorite author is Jhumpa Lahiri. 56 00:03:08,032 --> 00:03:14,392 And my favorite book is The Lowland and I try to plug that book to everyone I meet. 57 00:03:14,482 --> 00:03:17,452 Um, if anyone has a chance , I would highly recommend reading it. 58 00:03:18,124 --> 00:03:24,394 I recently, uh, reset up my home office and have a standing desk, and I, um, now 59 00:03:24,394 --> 00:03:28,354 have this other wall behind me, which of course your audience won't be able to see. 60 00:03:28,354 --> 00:03:33,004 But, um, so I, I have to decide whether or not I want those things 61 00:03:33,004 --> 00:03:36,394 to show up on, on video conferences. 62 00:03:36,514 --> 00:03:39,244 But, um, the standing desk is good, although I think 63 00:03:39,244 --> 00:03:40,264 I'm leaning on it right now. 64 00:03:40,514 --> 00:03:42,224 I'm joined the, the 2020s. 65 00:03:43,124 --> 00:03:43,934 Excellent. 66 00:03:44,834 --> 00:03:46,664 And rounding us out, Adama, how about you? 67 00:03:48,299 --> 00:03:48,839 Yeah. 68 00:03:48,839 --> 00:03:55,799 Um, I, I really like outdoor activities, outdoor fishing and, uh, hunting. 69 00:03:56,369 --> 00:04:01,616 Uh, people usually call me the man with two guns, one to kill pathogen, save 70 00:04:01,616 --> 00:04:08,816 life in in the city, and the second one to control some animal in the bush. 71 00:04:09,206 --> 00:04:10,286 So I really like that. 72 00:04:10,316 --> 00:04:10,526 Thank you. 73 00:04:11,472 --> 00:04:15,492 Alright, um, well I'm gonna tell you guys a little bit about 74 00:04:15,492 --> 00:04:18,052 a case and get your thoughts. 75 00:04:18,442 --> 00:04:23,332 So today we have an 18 month old male who presents with worsening 76 00:04:23,332 --> 00:04:27,136 respiratory distress after approximately three days of illness. 77 00:04:27,232 --> 00:04:31,912 The symptoms were initially mild with minor rhinorrhea, but have progressively 78 00:04:31,912 --> 00:04:36,962 worsened, and the patient is having rapidly worsening difficulty in 79 00:04:36,962 --> 00:04:39,302 breathing over the past 48 hours. 80 00:04:39,349 --> 00:04:42,469 The mother initially presented to a community hospital and was 81 00:04:42,469 --> 00:04:47,239 hospitalized, and later that patient was transported to a tertiary care center. 82 00:04:48,509 --> 00:04:53,069 The patient is otherwise healthy, has never had similar episodes to this, has 83 00:04:53,069 --> 00:04:57,509 no history of prior hospitalization, atopy, or a family history of 84 00:04:57,509 --> 00:04:59,969 asthma or other medical conditions. 85 00:05:00,389 --> 00:05:05,864 The patient lives in the city, has no contact with animals, but is unvaccinated 86 00:05:05,864 --> 00:05:07,574 and drinks unpasteurized milk. 87 00:05:08,174 --> 00:05:10,094 There are no known sick contacts. 88 00:05:10,364 --> 00:05:13,454 There's no family history of recurrent infections or autoimmune 89 00:05:13,454 --> 00:05:17,684 disease, and no additional family members, uh, attend daycare. 90 00:05:18,434 --> 00:05:23,024 On physical exam, the child has an O2 saturation of 88% on supplemental oxygen. 91 00:05:23,234 --> 00:05:29,684 He is tachycardic to 168 beats per minute and tachycardic to 75 breaths per minute. 92 00:05:30,134 --> 00:05:31,454 He is afebrile. 93 00:05:32,264 --> 00:05:36,584 Pertinent physical exam findings include a markedly exhausted appearance. 94 00:05:36,734 --> 00:05:41,174 He does respond to the physical exam by crying and is moving all extremities 95 00:05:41,174 --> 00:05:46,554 appropriately, but otherwise is, you know, diminished and uninterested, and not 96 00:05:46,554 --> 00:05:48,354 really interacting with folks around him. 97 00:05:48,889 --> 00:05:53,689 He has significant respiratory distress with tachypnea, head bobbing, nasal 98 00:05:53,689 --> 00:05:58,369 flaring, tracheal tugging, as well as intercostal and subcostal retractions. 99 00:05:58,759 --> 00:06:00,769 He has audible stridor at rest. 100 00:06:01,229 --> 00:06:06,239 His lungs are clear on auscultation and coating his nares is a thick gray 101 00:06:06,269 --> 00:06:09,839 nasal discharge, which appears to be adherent to the mucus membrane. 102 00:06:10,429 --> 00:06:15,409 He has bilateral tonsillar hypertrophy with a thick gray layer extending 103 00:06:15,409 --> 00:06:19,489 over the bilateral tonsils and adherent to surrounding structures. 104 00:06:19,859 --> 00:06:24,089 And so all of this is also associated with some bilateral cervical lymph adenopathy. 105 00:06:24,929 --> 00:06:26,939 All right, so you guys get a lot of information. 106 00:06:26,939 --> 00:06:28,589 What do you think is going on at the moment? 107 00:06:28,839 --> 00:06:31,899 The first and most important thing always to do is to make an anatomic 108 00:06:31,899 --> 00:06:35,259 diagnosis, and it looks like this patient has a membranous pharyngitis. 109 00:06:36,099 --> 00:06:40,419 So, I think that with a case like this, it's important to kind of break your 110 00:06:40,419 --> 00:06:43,329 differential diagnosis down by setting. 111 00:06:43,899 --> 00:06:46,479 I think you would be thinking about different things based 112 00:06:46,479 --> 00:06:47,709 on where you are in the world. 113 00:06:47,989 --> 00:06:54,559 So if you are in the United States, the most likely cause of 114 00:06:54,564 --> 00:06:58,069 membranous pharyngitis in a high income country, especially in people 115 00:06:58,069 --> 00:07:03,749 who are vaccinated, is going to be EBV, um, sometimes Arcanobacterium 116 00:07:03,749 --> 00:07:08,119 hemolyticum can also cause, uh, a membranous pharyngitis like picture. 117 00:07:08,599 --> 00:07:14,809 But given that this child is unvaccinated, even if you were in a high income setting, 118 00:07:14,859 --> 00:07:18,219 you would definitely think about something like diptheria, which is kind of the 119 00:07:18,219 --> 00:07:21,459 classic cause of a membranous pharyngitis. 120 00:07:22,059 --> 00:07:27,479 Um, and, you know, taking a step back, this patient is very, very sick. 121 00:07:27,769 --> 00:07:28,909 Really critically ill. 122 00:07:30,109 --> 00:07:35,929 So before you do this throat exam and find these kind of like very particular 123 00:07:35,929 --> 00:07:40,819 findings, you also need to consider other causes of really significant respiratory 124 00:07:40,819 --> 00:07:45,309 distress or severe respiratory distress, especially in the context of the stridor. 125 00:07:45,799 --> 00:07:49,879 Um, and in that case you might be thinking about croup. 126 00:07:49,909 --> 00:07:52,939 Obviously this is a very severe presentation for something like croup, 127 00:07:54,064 --> 00:07:56,764 which would make you think about like a community acquired bacterial 128 00:07:56,764 --> 00:08:00,454 tracheitis, which as most people are aware, is caused by Staph aureus. 129 00:08:00,964 --> 00:08:04,534 You would al also think about something like epiglottitis, um, 130 00:08:04,534 --> 00:08:08,704 which in the United States is more likely to be caused by a nontypeable 131 00:08:08,704 --> 00:08:11,524 H flu, um, or another organism. 132 00:08:11,524 --> 00:08:14,554 But, you know, outside the US where vaccination coverage is still 133 00:08:14,644 --> 00:08:19,054 low, Hib would still be what you would be thinking about there. 134 00:08:19,634 --> 00:08:23,534 And then obviously you'd be thinking about pneumonia, severe viral infections that 135 00:08:23,534 --> 00:08:25,244 could be causing respiratory distress. 136 00:08:25,454 --> 00:08:28,904 Obviously, they don't perfectly fit with the picture and given the degree of 137 00:08:28,904 --> 00:08:32,484 illness here, the fact that the patient is minimally responsive, you might be 138 00:08:32,484 --> 00:08:36,594 thinking about a systemic bacterial infection of some kind, may be associated 139 00:08:36,594 --> 00:08:40,914 with the localized picture, um, uh, a sepsis or a meningitis type picture. 140 00:08:41,284 --> 00:08:44,194 I think that those are the things to really consider in a patient like 141 00:08:44,254 --> 00:08:50,044 this, but primarily with your physical exam, you're thinking about causes of 142 00:08:50,044 --> 00:08:53,914 membranous pharyngitis, and I'll turn it over to Adama to, to kind of talk 143 00:08:53,914 --> 00:08:58,114 about how we might approach a patient like this in a resource limited setting. 144 00:08:58,414 --> 00:08:59,419 Thank you so much. 145 00:08:59,419 --> 00:08:59,859 Thank you. 146 00:09:00,069 --> 00:09:05,779 I think I will not repeat all you said, taking into, into account the clinical, 147 00:09:05,959 --> 00:09:08,359 uh, aspects that has been presented. 148 00:09:08,779 --> 00:09:14,079 So in uh, the resource constrained setting, uh, people might think first 149 00:09:14,129 --> 00:09:21,379 about a severe respiratory infection, or, uh, something like a foreign body 150 00:09:21,409 --> 00:09:30,781 in the upper respiratory, uh, level or tonsillitis, throat infection, angina. 151 00:09:30,871 --> 00:09:35,194 So that's the first thing we might think of. 152 00:09:35,764 --> 00:09:41,544 But with the presence of, uh, a pseudomembrane, which is thick, and 153 00:09:41,594 --> 00:09:50,816 adherent, that is something not very common in the past year, but we might 154 00:09:50,816 --> 00:09:58,796 think about diphtheria with this outbreak in our area in West Africa. 155 00:09:58,916 --> 00:10:00,806 So that's something to think about. 156 00:10:02,066 --> 00:10:07,826 So it's very difficult in the resource, uh, constrained setting to have a clear 157 00:10:07,826 --> 00:10:15,071 diagnosis at first glance because of the limited test available, diagnostic 158 00:10:15,086 --> 00:10:19,461 test to have a, a clear diagnosis as compared to the developed world. 159 00:10:20,056 --> 00:10:20,326 Yeah. 160 00:10:20,376 --> 00:10:21,666 Those are all very good points. 161 00:10:21,726 --> 00:10:27,726 Adama, I think another really difficult aspect of managing cases like this 162 00:10:27,786 --> 00:10:34,928 in resource limited settings is going to be the fact that oftentimes even 163 00:10:34,928 --> 00:10:40,148 in referral hospitals and national reference centers, it's very hard 164 00:10:40,148 --> 00:10:42,068 to find mechanical ventilators. 165 00:10:42,398 --> 00:10:45,818 So patients who have severe respiratory distress, no matter what the 166 00:10:45,818 --> 00:10:50,713 cause, it can be very difficult to appropriately treat these patients. 167 00:10:51,223 --> 00:10:55,333 And at this point, I think it's important to reveal that this patient 168 00:10:55,333 --> 00:11:01,183 was actually seen in a resource limited setting, in West Africa, and part of 169 00:11:01,183 --> 00:11:09,073 the reason why he was clearly hypoxic and had severe stridor, um, but wasn't 170 00:11:09,073 --> 00:11:13,543 intubated is because there wasn't mechanical ventilation available. 171 00:11:14,013 --> 00:11:19,893 In the United States or in a resource rich setting, people always think about 172 00:11:19,923 --> 00:11:22,683 kind of croup versus bronchiolitis. 173 00:11:23,043 --> 00:11:28,303 It's really bad when you have stridor, which is indicative of an upper airway 174 00:11:28,303 --> 00:11:31,363 obstruction of some kind, in this case, probably related to the pseudo 175 00:11:31,363 --> 00:11:36,303 membrane of the patient, and you have hypoxia because that means that your 176 00:11:36,573 --> 00:11:38,733 airway is literally constricting. 177 00:11:38,973 --> 00:11:39,063 Mm-hmm. 178 00:11:39,333 --> 00:11:44,673 Um, and that is usually an indication for intubation and mechanical ventilation, 179 00:11:45,273 --> 00:11:51,263 um, in a resource rich setting, but in a setting, in West Africa, since those 180 00:11:51,473 --> 00:11:55,913 resources are not available, oftentimes the best you can do is just oxygen. 181 00:11:56,903 --> 00:11:57,203 Yeah. 182 00:11:57,203 --> 00:11:59,813 I think one more thing to add is the training. 183 00:11:59,813 --> 00:12:04,283 Even if the ventilator is available, people are not trained how to use 184 00:12:04,283 --> 00:12:08,345 this properly and to make a good surveillance of the patient that 185 00:12:08,345 --> 00:12:10,895 will be put on on ventilation. 186 00:12:11,225 --> 00:12:15,950 So, beside that, the training on how to, uh, make a good intubation. 187 00:12:16,550 --> 00:12:16,820 Yeah. 188 00:12:16,880 --> 00:12:22,210 So to clear the airway, uh, is not also something that is 189 00:12:22,260 --> 00:12:24,430 right on hand in our context. 190 00:12:24,910 --> 00:12:29,941 I would also add that, Adama, to add to what you just, um, said, an additional 191 00:12:29,941 --> 00:12:34,231 aspect to take into account is a monitoring that ventilation requires. 192 00:12:34,681 --> 00:12:38,511 And, to take it a step further, even if you have the machine and even if you have 193 00:12:38,511 --> 00:12:42,471 absolutely trained to do the intubation, and which in this case is very, of 194 00:12:42,471 --> 00:12:44,391 course, medically complex in any setting. 195 00:12:44,511 --> 00:12:44,601 Mm-hmm. 196 00:12:44,931 --> 00:12:45,381 Um. 197 00:12:46,181 --> 00:12:51,881 Uh, to be able to monitor a patient who is on ventilation, you need for 198 00:12:51,881 --> 00:12:56,021 capacity, for example, to do arterial blood gas measurements, which are not 199 00:12:56,021 --> 00:13:01,021 possible routinely, whether it's from lack of equipment or lack of reagents 200 00:13:01,021 --> 00:13:03,541 for the use of any available equipment. 201 00:13:03,901 --> 00:13:06,211 So those are additional limitations. 202 00:13:06,628 --> 00:13:12,173 So with that, we can talk a little bit about what our thought process was 203 00:13:12,233 --> 00:13:15,553 and has been during cases like this. 204 00:13:15,943 --> 00:13:19,723 So we talked about EBV being a potential cause. 205 00:13:20,263 --> 00:13:23,863 Membranous pharyngitis is a relatively rare manifestation of EBV. 206 00:13:24,253 --> 00:13:28,383 So if you see multiple cases of membranous pharyngitis in an 207 00:13:28,383 --> 00:13:32,703 unvaccinated population, especially in a resource limited setting, it's 208 00:13:32,823 --> 00:13:36,443 not likely to all be related to EBV. 209 00:13:36,783 --> 00:13:40,563 It's much more likely to be related to diphtheria, especially if you 210 00:13:40,563 --> 00:13:44,733 have confirmatory diagnostic testing for at least a few of those cases. 211 00:13:45,123 --> 00:13:47,643 And that's kind of what you know happened here. 212 00:13:47,643 --> 00:13:53,893 This patient was not formally diagnosed with diphtheria, uh, with lab testing, 213 00:13:54,328 --> 00:13:58,408 but given that there were multiple cases that happened around the same 214 00:13:58,408 --> 00:14:03,898 time in the context of a West African outbreak, the clinical diagnosis that 215 00:14:03,898 --> 00:14:06,248 was given to this patient was diphtheria. 216 00:14:06,828 --> 00:14:12,428 And with that, I think it's important to discuss some of the features of 217 00:14:12,428 --> 00:14:16,128 diphtheria, some of the things to look out for with diphtheria, some of the 218 00:14:16,128 --> 00:14:20,038 clinical manifestations . Um, and for that I will turn over to Dr. Tapia. 219 00:14:20,378 --> 00:14:20,768 All right. 220 00:14:21,398 --> 00:14:25,328 So diphtheria is caused by one of three Corynebacterium. 221 00:14:25,348 --> 00:14:30,448 That's Corynebacterium diptheriae, ulcerans, or, pseudotuberculosis. 222 00:14:30,888 --> 00:14:36,908 On gram stain you have a gram-positive pleomorphic rods that stain irregularly. 223 00:14:37,498 --> 00:14:43,208 They grow best on media containing sheep's blood and fosfomycin, or 224 00:14:43,268 --> 00:14:47,458 on, uh, Tindale medium, which is tellurite medium with cysteine. 225 00:14:48,268 --> 00:14:53,518 Only the strains containing the beta pro phage or related phages are toxigenic, 226 00:14:54,118 --> 00:15:00,028 and it's the expression of the toxin, um, is based on the nutritional environment. 227 00:15:00,608 --> 00:15:04,868 The toxin is composed of two subunits, an A and B sub unit, and it's the 228 00:15:04,868 --> 00:15:09,968 B sub unit that allows for entry in the A subunit, which exerts its 229 00:15:09,968 --> 00:15:14,618 toxic effect through inhibition of protein synthesis in the host cell. 230 00:15:15,703 --> 00:15:20,023 The toxin is highly expressed in the absence of iron and, the phage 231 00:15:20,023 --> 00:15:26,023 mediates production of toxin and can be transferred in vitro and in vivo. 232 00:15:26,953 --> 00:15:29,743 There are a number of clinical manifestations. 233 00:15:29,773 --> 00:15:33,583 One is nasal diphtheria, which occurs primarily in infants. 234 00:15:34,033 --> 00:15:37,333 And it begins as a cold and a thick membrane that develops. 235 00:15:37,563 --> 00:15:40,708 This is the less lethal form of the disease. 236 00:15:41,008 --> 00:15:45,178 There is tonsillar diptheria where it obviously affects the tonsils and pharynx, 237 00:15:45,548 --> 00:15:48,668 which can coexist with nasal diphtheria. 238 00:15:48,818 --> 00:15:53,738 It begins with one to two days of URI symptoms, followed by a pseudo membrane. 239 00:15:53,828 --> 00:15:57,318 The membrane can expand and extend into the larynx and 240 00:15:57,318 --> 00:15:59,148 trachea causing suffocation. 241 00:15:59,508 --> 00:16:06,108 Cervical lymphadenopathy is present and causes a bulls neck or obliterative edema. 242 00:16:06,673 --> 00:16:09,703 And this is the presentation that we're discussing here 243 00:16:09,703 --> 00:16:10,843 in the patient that we saw. 244 00:16:11,433 --> 00:16:17,743 There is also laryngeal diphtheria and cutaneous diphtheria and other 245 00:16:17,743 --> 00:16:22,753 manifestations include conjunctivitis, otitis media, and septic arthritis. 246 00:16:23,143 --> 00:16:26,993 It's important to note that there can be toxic complications of diphtheria. 247 00:16:27,013 --> 00:16:30,928 So in addition to these presentations, which can be 248 00:16:30,928 --> 00:16:32,548 very acute and life-threatening. 249 00:16:32,788 --> 00:16:36,778 There can be additionally life-threatening complications, including myocarditis. 250 00:16:37,208 --> 00:16:40,268 That can begin, uh, week between two and six. 251 00:16:40,268 --> 00:16:41,408 Typically week two. 252 00:16:41,948 --> 00:16:46,658 Um, this can occur in 10% of children and up to a two-thirds of them 253 00:16:46,998 --> 00:16:48,708 can present with severe illness. 254 00:16:48,808 --> 00:16:53,818 The occurrence of this complication can be predicted based on the extent of the 255 00:16:53,818 --> 00:17:00,418 pseudo membrane, and a delay in antitoxin administration usually increases the risk 256 00:17:00,838 --> 00:17:05,498 of this complication, and unfortunately there is a 50% mortality rate. 257 00:17:06,363 --> 00:17:08,073 There can also be neuropathies. 258 00:17:08,103 --> 00:17:12,543 Um, two out of three children with severe illness develop these and 259 00:17:12,543 --> 00:17:16,203 they occur typically three to six weeks after illness and can be motor, 260 00:17:16,203 --> 00:17:19,773 symmetric and indistinguishable from Guillain Barre syndrome. 261 00:17:20,443 --> 00:17:24,953 It's a pretty complex presentation sometimes and again can be very, 262 00:17:24,953 --> 00:17:26,423 very serious and life threatening. 263 00:17:26,924 --> 00:17:27,224 Yeah. 264 00:17:27,224 --> 00:17:35,004 So, it's important to, to discuss what we know about diphtheria now. 265 00:17:35,224 --> 00:17:40,454 Diphtheria was kind of an illness which was declining internationally. 266 00:17:40,454 --> 00:17:44,474 There used to be millions of cases in the 1980s, but we've seen a 267 00:17:44,474 --> 00:17:48,944 resurgence of diptheria primarily in regions that are war torn. 268 00:17:49,284 --> 00:17:53,664 Initially, like in Bangladesh, there was a huge outbreak in the 269 00:17:53,664 --> 00:17:59,254 late 2010s among the Rohingya, which were refugees from Myanmar. 270 00:17:59,614 --> 00:18:02,614 Then there was an outbreak in Yemen, and now currently there's 271 00:18:02,674 --> 00:18:04,474 an outbreak in West Africa. 272 00:18:04,774 --> 00:18:09,424 The latter outbreak is most likely related to declining vaccination 273 00:18:09,424 --> 00:18:11,584 coverage in the context of COVID-19. 274 00:18:12,094 --> 00:18:18,040 Um, but because a lot of previous outbreaks were in eras when 275 00:18:18,040 --> 00:18:23,620 we had less data, there was a paper, uh, that came out in 2020. 276 00:18:24,370 --> 00:18:26,310 Written by Sean Truelove. 277 00:18:26,800 --> 00:18:32,540 They attempted to look at outbreaks over the last 100 years to put together some 278 00:18:32,540 --> 00:18:35,060 of the major features of the illness. 279 00:18:35,430 --> 00:18:38,760 So they looked at like 7,000 articles. 280 00:18:39,105 --> 00:18:43,395 Ended up including about 800 articles, which spanned outbreaks over the 281 00:18:43,395 --> 00:18:48,945 last 100 years and determined the transmissibility of diphtheria, the 282 00:18:48,945 --> 00:18:54,775 case fatality rate overall, and multiple other features of the illness, which are 283 00:18:54,775 --> 00:18:59,135 important to note in an era when we see increasing transmission of the disease. 284 00:18:59,429 --> 00:19:02,369 What they determined is that the case fatality rate of 285 00:19:02,369 --> 00:19:05,189 diptheria is about 29% overall. 286 00:19:05,619 --> 00:19:09,969 Kids who are older are less likely to die. 287 00:19:10,239 --> 00:19:14,109 Kids who are vaccinated obviously are less likely to die. 288 00:19:14,589 --> 00:19:20,229 And those treated with antitoxin are significantly less likely to die. 289 00:19:20,229 --> 00:19:28,354 So the odds of someone dying after being given antitoxin is 0.24 in contrast 290 00:19:28,354 --> 00:19:30,394 to people who are not given antitoxin. 291 00:19:30,694 --> 00:19:37,234 The best way to protect yourself from diphtheria, obviously, is to 292 00:19:37,234 --> 00:19:40,254 have universal vaccine coverage. 293 00:19:40,714 --> 00:19:45,564 Having three doses of vaccination is 87% protective against illness. 294 00:19:45,654 --> 00:19:48,144 It's not 100% protective against illness. 295 00:19:48,564 --> 00:19:52,484 Unfortunately, developing natural infection does not confer 296 00:19:52,484 --> 00:19:54,069 immunity against diptheria. 297 00:19:54,609 --> 00:20:01,529 The typical schedule for diptheria vaccine is obviously the DTaP vaccine. 298 00:20:01,529 --> 00:20:07,189 So it's at two months, four months, six months, 15 to 18 months, and 299 00:20:07,189 --> 00:20:10,199 one dose at four to six years. 300 00:20:10,709 --> 00:20:17,995 Children can get the vaccine afterwards, especially in the context of an outbreak, 301 00:20:18,205 --> 00:20:23,545 the problem if you're greater than seven years old is if you get either 302 00:20:23,545 --> 00:20:26,365 Tdap or the Td containing vaccine. 303 00:20:26,785 --> 00:20:33,725 The amount of diphtheria antigen present in that vaccine is actually 304 00:20:33,725 --> 00:20:37,745 significantly lower than what's present in the DTaP vaccine. 305 00:20:38,570 --> 00:20:44,210 So the protective efficacy of that version of vaccine is not well described 306 00:20:44,750 --> 00:20:46,710 as opposed to the DTaP vaccine. 307 00:20:47,370 --> 00:20:53,610 As far as management of diptheria, there are two things that are critical. 308 00:20:54,090 --> 00:21:01,020 One is antitoxin, which reduces mortality by about 76%. 309 00:21:01,650 --> 00:21:04,350 And the second thing is antibiotics. 310 00:21:05,085 --> 00:21:07,425 Antibiotics reduce transmissibility. 311 00:21:08,355 --> 00:21:11,055 Antitoxin reduces mortality. 312 00:21:11,625 --> 00:21:13,425 The two are mutually exclusive. 313 00:21:13,845 --> 00:21:16,035 Antibiotics do not impact mortality. 314 00:21:16,485 --> 00:21:21,350 Antitoxin does not impact transmissibility, so the problem 315 00:21:21,650 --> 00:21:31,565 is in most cases where diptheria is still present antitoxin is not 316 00:21:31,565 --> 00:21:35,765 widely available, which leads to very, very high mortality rates. 317 00:21:38,375 --> 00:21:44,735 The other issue is that we, we have seen increasing resistance to penicillin, 318 00:21:45,005 --> 00:21:49,145 which was one of the first line treatments for diptheria to reduce 319 00:21:49,145 --> 00:21:54,875 transmissibility, making macrolides kind of the first line treatment. 320 00:21:55,640 --> 00:22:01,440 But macrolides, in some places where diptheria is present may not be as widely 321 00:22:01,440 --> 00:22:05,970 available as penicillin and may not be guaranteed by the government making 322 00:22:05,970 --> 00:22:08,100 it difficult to control transmission. 323 00:22:08,580 --> 00:22:12,120 The other thing is that infection control practices are, are, are 324 00:22:12,120 --> 00:22:15,780 difficult to enforce, especially in resource limited settings. 325 00:22:16,020 --> 00:22:17,910 So if kids are in an open unit. 326 00:22:19,665 --> 00:22:26,195 You can't really enforce droplet transmission precautions, and that kind 327 00:22:26,195 --> 00:22:29,405 of makes it easy for the disease to spread even in the hospital setting. 328 00:22:29,794 --> 00:22:34,784 Now, the main points of diagnosis. 329 00:22:35,084 --> 00:22:41,414 So there are two things that you need to be able to do, especially in the 330 00:22:41,414 --> 00:22:43,694 context of a small number of cases. 331 00:22:43,724 --> 00:22:46,244 In an outbreak, it's a little different. 332 00:22:47,054 --> 00:22:51,104 But when you have a small number of cases, if for instance, someone 333 00:22:51,104 --> 00:22:54,254 presents to the hospital and you think that they have diptheria in the 334 00:22:54,254 --> 00:22:59,684 context of the United States, you need to be able to isolate the organism. 335 00:23:00,074 --> 00:23:05,984 So you take a swab and you want to get either on the tonsils or around the 336 00:23:05,984 --> 00:23:11,394 pseudo membrane, and then send that swab for culture and actually grow it. 337 00:23:11,694 --> 00:23:15,804 And then demonstrate phenotypic toxin production through 338 00:23:15,894 --> 00:23:17,634 something called the Elek Test. 339 00:23:18,174 --> 00:23:25,194 Now, the problem is that the Elek test requires antitoxin as one of its reagents. 340 00:23:25,554 --> 00:23:29,934 If you don't have antitoxin, which is the case in many resource limited 341 00:23:29,934 --> 00:23:36,234 settings, it can be very difficult, um, to actually perform the Elek test. 342 00:23:36,234 --> 00:23:40,284 So you have no evidence of phenotypic toxin production in that setting. 343 00:23:40,944 --> 00:23:45,174 Also, if you don't have great microbiologic capacity in 344 00:23:45,174 --> 00:23:49,734 your country, it can also be difficult to culture the organism. 345 00:23:50,004 --> 00:23:53,274 And keep in mind that many of these patients get pretreated. 346 00:23:53,574 --> 00:23:57,014 So if they're very sick at the time of presentation to another 347 00:23:57,014 --> 00:24:02,774 hospital, then they may get antibiotics as soon as they show up. 348 00:24:03,044 --> 00:24:07,574 So their culture will be sterile by the time that they present to a hospital 349 00:24:07,574 --> 00:24:09,464 where the test is actually performed. 350 00:24:10,184 --> 00:24:15,164 So another way that you can make the diagnosis theoretically, 351 00:24:15,464 --> 00:24:17,204 is through the use of PCR. 352 00:24:17,444 --> 00:24:23,174 The problem with PCR is that you can get what looks like a toxigenic 353 00:24:23,174 --> 00:24:30,489 Corynebacterium diphtheriae, but the presence of the toxigenic gene 354 00:24:30,849 --> 00:24:35,379 doesn't actually mean that the toxin is expressed phenotypically. 355 00:24:35,659 --> 00:24:39,999 So Elek testing actually tells you whether or not the isolate is phenotypically 356 00:24:39,999 --> 00:24:47,049 producing toxin, but PCR can give you an idea of whether or not toxin is 357 00:24:47,139 --> 00:24:50,979 present in the isolate, doesn't tell you whether or not it's actually expressed. 358 00:24:51,399 --> 00:24:55,449 So it's kind of challenging. 359 00:24:55,989 --> 00:25:02,133 You need to demonstrate phenotypic toxin production, but if you don't have 360 00:25:02,133 --> 00:25:06,513 the ability to culture, you can't do that, so sometimes PCR is all you have. 361 00:25:06,993 --> 00:25:11,913 And only toxigenic diptheria can produce the manifestations 362 00:25:11,913 --> 00:25:13,083 that we're talking about. 363 00:25:13,263 --> 00:25:17,223 Non toxigenic Cornyebacterium diphtheriae can produce other things 364 00:25:17,223 --> 00:25:20,683 like myocarditis, conjunctivitis, the things that we were discussing, 365 00:25:20,883 --> 00:25:25,003 especially in immunocompromised patients, but only toxigenic diphtheria 366 00:25:25,053 --> 00:25:28,353 can produce this aggressive tonsillar disease that we're talking about. 367 00:25:28,833 --> 00:25:35,073 So in the context of just a few cases, culture is vital. 368 00:25:35,733 --> 00:25:42,723 But in the context of an outbreak, you either have to use PCR knowing that it's 369 00:25:42,723 --> 00:25:49,713 an imperfect surrogate for culture, or you have to make the clinical diagnosis. 370 00:25:50,523 --> 00:25:54,693 In Mali, oftentimes the clinical diagnosis is all we have. 371 00:25:55,103 --> 00:26:00,293 Most of our patients were pretreated with antibiotics, and about 52 patients 372 00:26:00,293 --> 00:26:04,673 were ultimately tested, but only one or two had positive cultures. 373 00:26:05,063 --> 00:26:09,263 Whereas when we use PCR, we find we found higher positivity rates. 374 00:26:10,523 --> 00:26:14,783 So that is kind of like a primer on the diagnosis of diptheria. 375 00:26:15,543 --> 00:26:19,703 It would be good to talk a little bit about antitoxin, and its 376 00:26:19,733 --> 00:26:22,893 restricted availability in the region. 377 00:26:22,893 --> 00:26:25,893 And I, I think Adama maybe if, if you could talk about that. 378 00:26:26,463 --> 00:26:28,033 Yeah, it's very sad. 379 00:26:28,033 --> 00:26:33,638 It's very heartbreaking hearing that 76% would have been saved 380 00:26:33,698 --> 00:26:36,308 if antitoxin, uh, were available. 381 00:26:36,308 --> 00:26:39,458 So that's something that, uh, uh. 382 00:26:40,928 --> 00:26:44,228 Is, uh, making me very, very sad. 383 00:26:44,828 --> 00:26:50,208 You know, over 50 suspected cases that have been identified in Malian 384 00:26:50,228 --> 00:26:52,588 Bamako here, at Gabriel Toure. 385 00:26:53,313 --> 00:26:55,453 All of them unfortunately died. 386 00:26:55,693 --> 00:27:00,313 So that's very, very sad because the anti-toxin is 387 00:27:00,313 --> 00:27:02,323 not available in the country. 388 00:27:02,413 --> 00:27:06,863 The only thing that we were able to implement is, uh, the vaccination 389 00:27:06,983 --> 00:27:12,323 around, uh, each suspected case, but the case themself, we were not 390 00:27:12,323 --> 00:27:16,733 able to save them with something that is available elsewhere. 391 00:27:17,063 --> 00:27:21,593 So that's really, uh, a big challenge. 392 00:27:22,013 --> 00:27:27,568 So, we also mentioned some of the challenge, that's the vaccine coverage. 393 00:27:27,628 --> 00:27:31,708 Recently, Anna Roose and a team in Mali here. 394 00:27:32,098 --> 00:27:37,468 They publish on vaccine coverage after rotavirus vaccine introduction 395 00:27:37,468 --> 00:27:39,208 in our national immunization. 396 00:27:39,628 --> 00:27:43,908 So the vaccination coverage is really low, below what is 397 00:27:43,918 --> 00:27:46,563 expected to be the acceptable one. 398 00:27:46,563 --> 00:27:50,008 So it was around 86% vaccine coverage. 399 00:27:50,278 --> 00:27:56,598 So with the Covid pandemic and vaccine hesitancy, public unrest 400 00:27:56,668 --> 00:28:00,108 within the country, within the region, all these contribute to 401 00:28:01,083 --> 00:28:03,253 this decreased vaccine coverage. 402 00:28:03,343 --> 00:28:09,203 So making more vulnerable people, uh, and children, subject to 403 00:28:09,263 --> 00:28:11,693 this preventable disease. 404 00:28:12,533 --> 00:28:15,864 I wonder if, do you guys think it would be helpful to talk about 405 00:28:16,921 --> 00:28:19,771 management of household contacts? 406 00:28:19,771 --> 00:28:24,571 Like Adama when with these patients, caretakers, relatives, other members, 407 00:28:24,791 --> 00:28:26,591 did you provide antibiotics to those? 408 00:28:26,591 --> 00:28:29,391 Is that something that was considered. 409 00:28:29,563 --> 00:28:30,133 Yeah, absolutely. 410 00:28:30,133 --> 00:28:35,083 It's really important to prevent the spread of the disease by 411 00:28:35,553 --> 00:28:39,843 preventive antibiotics and vaccination of the close contact. 412 00:28:40,353 --> 00:28:48,573 So this patient, the route from their home to the health facility, the final 413 00:28:48,623 --> 00:28:51,323 endpoint, is really sometime long. 414 00:28:51,323 --> 00:28:53,883 They pass by several parts. 415 00:28:54,303 --> 00:28:57,353 Some are seen by traditional healers. 416 00:28:57,353 --> 00:29:00,023 Some go to, uh, CSComs (Centres de Santé Communauté) level. 417 00:29:00,023 --> 00:29:05,023 CSComs is the first level of the overall health system, so there are a lot of 418 00:29:05,053 --> 00:29:08,538 contact to be monitored, to be treat. 419 00:29:08,538 --> 00:29:12,978 So looking at the resource that is need for that and the, 420 00:29:13,603 --> 00:29:17,893 movement of the, the people in the country, it's really difficult. 421 00:29:17,893 --> 00:29:24,423 It's really very challenging to get hand on all the potential contact and 422 00:29:24,483 --> 00:29:26,613 prevent the spread of the illness. 423 00:29:26,863 --> 00:29:30,958 This approach is used for some of the suspected case administration 424 00:29:30,958 --> 00:29:36,448 of antibiotic and vaccination, but it's not done for all, unfortunately. 425 00:29:37,018 --> 00:29:37,288 Yeah, 426 00:29:37,594 --> 00:29:40,804 And just to piggyback off of that, um, the Red Book actually has 427 00:29:40,804 --> 00:29:44,444 recommendations on how to manage, uh, diptheria and diptheria exposure. 428 00:29:44,444 --> 00:29:47,984 First of all, the, the, the primary thing that you need to do. 429 00:29:48,434 --> 00:29:50,054 This is why cultures are so important. 430 00:29:50,144 --> 00:29:53,024 You need to document elimination of toxigenic strains. 431 00:29:53,474 --> 00:29:57,684 Um, so you need two consecutive negative cultures, taken 24 432 00:29:57,684 --> 00:29:59,784 hours apart after therapy. 433 00:30:00,544 --> 00:30:05,371 You also need to assess everyone in the household and close contacts, to see if 434 00:30:05,371 --> 00:30:07,771 they're carriers of toxigenic strains. 435 00:30:08,506 --> 00:30:13,396 All close contacts should also receive antimicrobial prophylaxis with either 436 00:30:13,426 --> 00:30:15,736 oral erythromycin or penicillin. 437 00:30:16,156 --> 00:30:19,306 Um, and if they're carriers, then they need to be treated. 438 00:30:20,086 --> 00:30:27,006 Those patients who are carriers need to be treated for 10 to 14 days with oral 439 00:30:27,006 --> 00:30:34,596 erythromycin or, or azithromycin for five days, or one dose of IM penicillin. 440 00:30:35,166 --> 00:30:37,476 Now that's what the Red Book says. 441 00:30:37,836 --> 00:30:42,766 Given that globally there are increasing resistance rates to penicillin. 442 00:30:44,596 --> 00:30:51,946 The WHO recommends macrolide antibiotics for diptheria period over penicillin. 443 00:30:52,426 --> 00:30:56,776 Um, if you are a carrier, just like someone who has been treated, you need 444 00:30:56,776 --> 00:30:58,666 two consecutive negative cultures. 445 00:30:59,001 --> 00:31:02,181 If you're still positive, you need an additional 10 days of oral erythromycin. 446 00:31:02,751 --> 00:31:05,661 All patients need to be on droplet precautions until they've completed 447 00:31:05,661 --> 00:31:07,521 therapy and they're culture negative. 448 00:31:07,881 --> 00:31:12,121 And then all close contacts, in addition to being tested for active 449 00:31:12,121 --> 00:31:16,256 surveillance and getting antibiotic prophylaxis to, you need to have 450 00:31:17,221 --> 00:31:20,101 seven days of active surveillance. 451 00:31:20,431 --> 00:31:25,771 Everyone who's a close contact needs to receive a dose of DTaP, T dap or 452 00:31:25,771 --> 00:31:31,601 Td. So just, um, some things to keep in mind, uh, with regards to people 453 00:31:31,601 --> 00:31:36,681 who are, um, exposed to the disease, especially in a high resource setting. 454 00:31:37,067 --> 00:31:40,427 Now, I think we've also discussed the West Africa outbreak a lot. 455 00:31:40,827 --> 00:31:43,197 And I think it's important to put some numbers around it. 456 00:31:43,317 --> 00:31:49,137 We've had around 40,000 cases of diptheria throughout the West African region. 457 00:31:49,467 --> 00:31:52,047 The outbreak, I think, began in Mauritania. 458 00:31:52,452 --> 00:31:55,302 And then spread to regional countries. 459 00:31:55,752 --> 00:32:00,492 Um, there's probably significant undercounting the number of cases 460 00:32:00,492 --> 00:32:05,942 because most of this number is based on cases that are actually confirmed. 461 00:32:06,632 --> 00:32:12,002 Um, so as we discussed, it can be very hard to confirm a case of diptheria 462 00:32:12,302 --> 00:32:13,772 in a resource limited setting. 463 00:32:14,312 --> 00:32:21,002 Um, and we don't have great ideas of what the mortality rate is, but. 464 00:32:21,782 --> 00:32:27,801 You know, at least in a place like Mali, while we don't have the same numbers as 465 00:32:27,891 --> 00:32:33,681 in places like Nigeria, the mortality rate for confirmed cases has been very, very 466 00:32:33,681 --> 00:32:35,811 high because of the lack of antitoxin. 467 00:32:36,176 --> 00:32:40,916 I'll take another opportunity to ask Adama about unvaccinated children, period. 468 00:32:40,916 --> 00:32:44,606 So the reasons for unvaccinated children in the United States 469 00:32:44,846 --> 00:32:48,561 are different from unvaccinated children in a country like Mali. 470 00:32:49,071 --> 00:32:54,446 And I think that, you know, it is very uncommon to actually have unvaccinated 471 00:32:54,446 --> 00:33:00,026 children in Bamako, whereas it is much more common in rural areas. 472 00:33:00,026 --> 00:33:04,706 And I think what, um, Adama brought up is that the route that a baby takes 473 00:33:04,706 --> 00:33:07,586 to get to us in Bamako can be long. 474 00:33:07,616 --> 00:33:11,516 And he brought that up, but I don't know that he actually highlighted the fact 475 00:33:11,546 --> 00:33:16,996 that many of the cases that we saw in Bamako were actually from rural areas. 476 00:33:17,176 --> 00:33:17,506 Yeah. 477 00:33:17,656 --> 00:33:24,166 Um, and so maybe, um, Adama, if you could just talk a little bit more about zero 478 00:33:24,166 --> 00:33:26,746 vaccination, zero vaccinated babies. 479 00:33:26,746 --> 00:33:30,316 And that's actually, I forget what the term is now, Sara, but there is 480 00:33:30,316 --> 00:33:34,276 a term now in public health looking at zero that the zero vaccine 481 00:33:34,276 --> 00:33:35,236 babies or something like that. 482 00:33:35,241 --> 00:33:35,341 Mm-hmm. 483 00:33:35,421 --> 00:33:36,976 There's a term in public health. 484 00:33:36,976 --> 00:33:37,901 It's a zero dose targeting. 485 00:33:38,051 --> 00:33:38,746 Zero, yeah. 486 00:33:38,751 --> 00:33:39,341 Zero dose, thank you. 487 00:33:39,451 --> 00:33:39,941 Zero dose. 488 00:33:39,941 --> 00:33:40,301 Mm-hmm. 489 00:33:41,146 --> 00:33:41,236 Yeah. 490 00:33:41,236 --> 00:33:48,056 I think, uh, we have a lot of zero dose in in Bamako in a area 491 00:33:48,056 --> 00:33:52,066 where we found some suspected case of diphtheria in common six. 492 00:33:52,456 --> 00:33:58,216 So, but as you mentioned, most of the case were coming from the rural area outside 493 00:33:58,216 --> 00:34:04,711 Bamako, and all of them did not have the diphtheria vaccine previously or have a 494 00:34:04,849 --> 00:34:08,754 s reported by the parents few, uh, doses. 495 00:34:08,754 --> 00:34:14,784 So yeah, it's really important to have the zero dose number, the 496 00:34:15,234 --> 00:34:16,674 vulnera vulnerability of the children. 497 00:34:16,704 --> 00:34:20,994 So yeah, there are some project now working on that. 498 00:34:21,324 --> 00:34:27,704 I hope that will con to reduce the zero dose within our uh, region. 499 00:34:28,143 --> 00:34:34,113 Usually people, uh, said in our culturally that you will not die 500 00:34:34,173 --> 00:34:37,133 before the day you set with God. 501 00:34:37,193 --> 00:34:43,733 But, uh, we are seeing that people are dying before that day in our country and 502 00:34:43,913 --> 00:34:46,553 for something that is really preventable. 503 00:34:47,453 --> 00:34:52,073 So I think we need to resolve basic medical need all around the 504 00:34:52,073 --> 00:34:58,503 world to have equity in access of, uh, basic medical needs. 505 00:34:59,668 --> 00:35:00,138 Thank you. 506 00:35:00,644 --> 00:35:04,005 Thanks to Sumanth, Adama and Millie for joining us today. 507 00:35:04,740 --> 00:35:08,730 This is part of a series of vaccine preventable illness topics. 508 00:35:08,823 --> 00:35:13,494 Don't forget to check out episode 1 0 2 called Rubeola Response, as 509 00:35:13,524 --> 00:35:17,934 well as our last episode of Febrile entitled Old Scourges, New Surges. 510 00:35:19,112 --> 00:35:23,132 You can find more info on the website febrile podcast.com, where 511 00:35:23,132 --> 00:35:26,132 we have the Consult Notes, which are written supplements to the 512 00:35:26,132 --> 00:35:29,702 episodes with links to references, our library of ID infographics, 513 00:35:29,732 --> 00:35:30,842 and a link to our merch store. 514 00:35:32,042 --> 00:35:36,062 Febrile is produced with support from the IDSA, Infectious 515 00:35:36,062 --> 00:35:37,592 Diseases Society of America. 516 00:35:38,102 --> 00:35:40,982 Please reach out if you have any suggestions for future shows or want 517 00:35:40,982 --> 00:35:42,302 to be more involved with febrile. 518 00:35:42,602 --> 00:35:43,382 Thanks for listening. 519 00:35:43,562 --> 00:35:45,062 Stay safe and I'll see you next time.