1 00:00:00,000 --> 00:00:10,690 Sara Dong: Hi everyone, welcome to Febrile, a cultured podcast about 2 00:00:10,739 --> 00:00:12,180 all things infectious disease. 3 00:00:13,480 --> 00:00:17,080 We use consult questions to dive into ID clinical reasoning, diagnostics, 4 00:00:17,110 --> 00:00:18,510 and antimicrobial management. 5 00:00:18,950 --> 00:00:21,660 I'm Sara Dong, your host and a MedPeds ID doc. 6 00:00:21,780 --> 00:00:24,570 First, I did just want to announce some wonderful news. 7 00:00:24,889 --> 00:00:29,069 Febrile is now partnering with IDSA, who will be helping to produce 8 00:00:29,070 --> 00:00:31,020 and expand the podcast platform. 9 00:00:31,110 --> 00:00:35,130 So, super excited to continue to share ID knowledge with you and 10 00:00:35,130 --> 00:00:36,880 excitement about the field of ID. 11 00:00:37,019 --> 00:00:40,449 So I, of course, would love to just add a plug that I would always love 12 00:00:40,449 --> 00:00:44,419 to hear from you, especially if you want to join an episode of Febrile. 13 00:00:44,569 --> 00:00:48,660 Febrile really likes to highlight trainees and junior faculty in particular. 14 00:00:48,730 --> 00:00:52,610 So if you would like to come on as a representative for your fellowship 15 00:00:52,619 --> 00:00:56,160 program, or as an individual, I would love to welcome you to the show 16 00:00:56,160 --> 00:00:57,760 for an episode, just let me know. 17 00:00:58,639 --> 00:00:59,109 All right. 18 00:00:59,120 --> 00:01:02,320 So today we have a great multi level learner team from 19 00:01:02,320 --> 00:01:03,660 the University of Minnesota. 20 00:01:03,999 --> 00:01:04,720 Let's meet them. 21 00:01:05,060 --> 00:01:07,090 First up, we have Sophie Samson. 22 00:01:07,429 --> 00:01:10,830 Sophie is currently a third year medical student at the University 23 00:01:10,830 --> 00:01:12,230 of Minnesota Medical School. 24 00:01:12,800 --> 00:01:16,350 She plans to train in pediatrics and has a particular interest 25 00:01:16,379 --> 00:01:18,720 in pediatric ID and neurology. 26 00:01:19,049 --> 00:01:21,810 Sophie Samson: Hi, my name is Sophie, and I'm happy to be here. 27 00:01:22,380 --> 00:01:23,389 Sara Dong: Next, we have Dr. 28 00:01:23,389 --> 00:01:24,610 Kristen Bastug. 29 00:01:25,039 --> 00:01:28,389 Kristen is a pediatric ID fellow from the University of Minnesota. 30 00:01:28,550 --> 00:01:32,660 She is interested in the intersection of ID, global child health, climate 31 00:01:32,660 --> 00:01:34,039 change, and environmental health. 32 00:01:34,189 --> 00:01:35,410 Kristen Bastug: Hi, this is Kristen. 33 00:01:35,429 --> 00:01:36,550 Excited to be doing this. 34 00:01:37,039 --> 00:01:38,429 Sara Dong: And last but not least, we have Dr. 35 00:01:38,430 --> 00:01:39,289 Beth Thielen. 36 00:01:39,730 --> 00:01:43,380 Beth is an adult and pediatric ID physician scientist at 37 00:01:43,380 --> 00:01:44,640 the University of Minnesota. 38 00:01:44,920 --> 00:01:50,619 She was previously on episode number 19, Finding a Needle in a Haystack from 2021. 39 00:01:51,089 --> 00:01:54,619 She currently leads a lab that is particularly interested in understanding 40 00:01:54,619 --> 00:01:58,239 the factors that influence the severity of respiratory viral infections. 41 00:01:58,719 --> 00:02:01,799 In addition to that, she has clinical interest in the care of immunocompromised 42 00:02:01,820 --> 00:02:05,920 patients, travel and tropical medicine, and clinical immunology. 43 00:02:07,020 --> 00:02:08,039 Beth Thielen: Hi, this is Beth. 44 00:02:08,050 --> 00:02:09,150 Happy to be back. 45 00:02:09,540 --> 00:02:10,100 Sara Dong: All right. 46 00:02:10,110 --> 00:02:13,500 And as everyone's favorite cultured podcast, we would love 47 00:02:13,500 --> 00:02:16,930 to hear a little piece of culture that brings you happiness. 48 00:02:17,730 --> 00:02:20,180 Sophie Samson: Well, I am a pretty avid reader. 49 00:02:20,200 --> 00:02:25,370 So one of my favorite books in the past year is called Cloud Cuckoo Land. 50 00:02:25,829 --> 00:02:31,910 And it is, um, set in multiple different centuries with a cast of characters and 51 00:02:31,910 --> 00:02:34,409 they're all intertwined in some way. 52 00:02:34,409 --> 00:02:38,155 And it's kind of a, a book that's an ode to book lovers in 53 00:02:38,155 --> 00:02:40,045 a way, so I really enjoyed that. 54 00:02:41,125 --> 00:02:41,725 Sara Dong: I love that. 55 00:02:41,734 --> 00:02:46,604 So someone mentioned that on Febrile before and I bought it and it's 56 00:02:46,604 --> 00:02:51,835 actually sitting like right off camera as my like next selection to read. 57 00:02:51,894 --> 00:02:52,475 I love it. 58 00:02:52,905 --> 00:02:54,275 Beth Thielen: I think I heard about it from one of the 59 00:02:54,275 --> 00:02:56,085 Curbsiders podcasts, actually. 60 00:02:56,115 --> 00:02:58,695 Sara Dong: Yeah, it's good. 61 00:02:58,695 --> 00:03:00,425 It means multiple people liked it. 62 00:03:00,435 --> 00:03:02,224 Just another endorsement. 63 00:03:03,185 --> 00:03:03,805 Kristen Bastug: Well, that's great. 64 00:03:03,845 --> 00:03:09,745 Um, I like to read as well, but I actually saw a really cool Netflix show recently. 65 00:03:09,860 --> 00:03:11,120 Life on our planet. 66 00:03:11,620 --> 00:03:17,100 Um, so it's a documentary style film with some CGI graphics. 67 00:03:17,170 --> 00:03:20,659 Um, actually Morgan Freeman narrates it, but they go through some of the 68 00:03:20,659 --> 00:03:24,829 really interesting geologic changes of our planet and then the ecosystem 69 00:03:24,829 --> 00:03:25,950 changes that were part of it. 70 00:03:26,270 --> 00:03:29,619 But I just really loved seeing the reimagined like graphic 71 00:03:29,630 --> 00:03:32,940 representation of these weird animals that like hadn't quite evolved yet. 72 00:03:33,530 --> 00:03:34,780 Um, I thought it was a lot of fun. 73 00:03:35,255 --> 00:03:35,815 Sara Dong: Very cool. 74 00:03:36,855 --> 00:03:41,005 Beth Thielen: Well, one of my culture moments is that during the pandemic, 75 00:03:41,025 --> 00:03:44,235 I took up a new hobby, which was learning to play the accordion. 76 00:03:44,645 --> 00:03:47,755 Just a little bit of a realization of a lifelong dream. 77 00:03:48,544 --> 00:03:52,644 And I play in an accordion group, and we had an opportunity for our group 78 00:03:52,644 --> 00:03:57,507 to travel together to eastern Italy to a small town called Castelfidardo, 79 00:03:57,895 --> 00:04:01,415 which is home of both the Guinness Book of World Records world largest 80 00:04:01,415 --> 00:04:05,955 accordion, which I was able to play, um, and we were able to tour an accordion 81 00:04:05,955 --> 00:04:09,765 factory, which is a kind of ground zero for the manufacturer of accordions. 82 00:04:09,795 --> 00:04:13,554 And so, uh, that is, that is the, my, my piece of culture for today. 83 00:04:14,454 --> 00:04:15,915 Sara Dong: That is amazing. 84 00:04:16,854 --> 00:04:17,805 I love it so much. 85 00:04:18,415 --> 00:04:19,055 Awesome. 86 00:04:19,055 --> 00:04:22,335 Well, I will hand it over to Sophie to get us started. 87 00:04:23,065 --> 00:04:23,515 Sophie Samson: Yeah. 88 00:04:23,525 --> 00:04:27,265 So I will start by telling you all a little bit about our patient.. 89 00:04:28,055 --> 00:04:32,525 So, our patient is a seven year old girl who presented to the ED a few days before 90 00:04:32,735 --> 00:04:37,605 with an acute onset seizure, headache, fever, and largely intact cognition. 91 00:04:38,245 --> 00:04:40,825 On the morning of admission, she experienced a right 92 00:04:40,825 --> 00:04:42,115 sided temporal headache. 93 00:04:42,564 --> 00:04:45,834 She then developed abdominal pain with one episode of emesis. 94 00:04:46,615 --> 00:04:50,255 She laid down and was found drooling and chewing with the right side of her mouth. 95 00:04:50,724 --> 00:04:55,245 Her eyes were open, but not focused, and she developed left sided, circular 96 00:04:55,265 --> 00:04:59,015 arm movements with associated urinary incontinence and tongue biting. 97 00:04:59,645 --> 00:05:03,934 She was not interactive, and the episode lasted about one hour, terminating 98 00:05:03,934 --> 00:05:06,205 with benzodiazepine given by EMS. 99 00:05:07,169 --> 00:05:12,559 In the ED, she had a low grade fever to 104 degrees Fahrenheit, and initial 100 00:05:12,559 --> 00:05:18,599 workup showed mild leukocytosis, elevated absolute neutrophil count, normal CMP 101 00:05:18,619 --> 00:05:23,199 except for elevated phosphorus, and inflammatory markers within normal limits. 102 00:05:23,940 --> 00:05:29,940 Infectious workup included a group A strep PCR, and a respiratory viral 103 00:05:29,940 --> 00:05:31,924 panel, which were both negative. 104 00:05:32,844 --> 00:05:36,525 Kristen, if you got a call based on this information, what are you 105 00:05:36,534 --> 00:05:40,184 thinking about at this point in terms of differential diagnosis, and what are 106 00:05:40,184 --> 00:05:42,044 you thinking about doing for management? 107 00:05:43,254 --> 00:05:44,604 Kristen Bastug: Yeah, thanks Sophie. 108 00:05:44,674 --> 00:05:48,224 Um, so at this point, I think we need to keep our differential 109 00:05:48,224 --> 00:05:53,219 pretty broad and consider first any etiologies that could be emergent. 110 00:05:53,659 --> 00:05:57,520 When I hear her presentation, the symptoms of headache, emesis, and 111 00:05:57,520 --> 00:06:01,020 focal seizure like activity raise my concern that there could be an 112 00:06:01,030 --> 00:06:02,770 intracranial process occurring. 113 00:06:03,429 --> 00:06:06,679 An intracranial hemorrhage could present this way, so I think we 114 00:06:06,679 --> 00:06:10,169 need to consider some head imaging to rule out an acute bleed. 115 00:06:10,750 --> 00:06:14,950 Her low grade fever and leukocytosis in the context of a seizure could 116 00:06:14,950 --> 00:06:16,520 be due to the seizure itself. 117 00:06:16,770 --> 00:06:20,359 However, I also want to consider infectious etiologies that could 118 00:06:20,359 --> 00:06:21,409 have triggered the seizure. 119 00:06:21,990 --> 00:06:26,590 At 7 years old, she is older than I would expect for someone having a febrile 120 00:06:26,600 --> 00:06:30,539 seizure, so I would like to obtain some additional diagnostic studies 121 00:06:30,539 --> 00:06:32,299 to help us investigate the etiology. 122 00:06:33,229 --> 00:06:37,000 I would recommend a lumbar puncture so that we can obtain the cerebrospinal 123 00:06:37,000 --> 00:06:40,749 fluid studies in order to evaluate further for an infectious cause. 124 00:06:41,424 --> 00:06:46,145 I would send meningitis and encephalitis PCR panel in addition to the standard 125 00:06:46,145 --> 00:06:50,575 cell count, glucose, protein, and aerobic culture on the CSF fluid. 126 00:06:51,604 --> 00:06:56,014 The meningitis encephalitis panel doesn't test for all pathogens, but 127 00:06:56,015 --> 00:06:59,115 it can test for several pathogens that are on my differential. 128 00:06:59,464 --> 00:07:03,094 These would include Streptococcus pneumoniae and Herpes Simplex Virus. 129 00:07:03,865 --> 00:07:04,655 Listeria and E. 130 00:07:04,655 --> 00:07:08,885 coli are less common at her age of seven, but are still possible. 131 00:07:09,365 --> 00:07:13,945 I would also consider Staphylococcus aureus, and if she is unvaccinated, 132 00:07:13,994 --> 00:07:17,055 then Haemophilus influenzae would be a higher possibility. 133 00:07:17,844 --> 00:07:21,685 Enterovirus is another one that comes to my mind, particularly in the summertime. 134 00:07:23,424 --> 00:07:24,184 Beth Thielen: Thanks, Kristen. 135 00:07:24,195 --> 00:07:27,590 That's a great, uh, kind of, discussion of your thought process. 136 00:07:27,999 --> 00:07:31,419 Um, I did also wanna highlight that since we're discussing the possibility of both 137 00:07:31,649 --> 00:07:36,159 head imaging and an LP in a patient whom we're, uh, ruling out bacterial meningitis 138 00:07:36,164 --> 00:07:39,489 that we should, uh, think, you know, think about some of the literature around this. 139 00:07:39,494 --> 00:07:43,450 And specifically I wanted to bring up a, uh, a, that the topic of CT and, and 140 00:07:43,450 --> 00:07:46,989 lumbar puncture was recently discussed in the Choosing Wisely campaign, uh, 141 00:07:46,989 --> 00:07:48,640 as something that we do for no reason. 142 00:07:48,939 --> 00:07:52,450 And, uh, importantly I think they make this dis-, we make this distinction 143 00:07:52,455 --> 00:07:55,599 between patients at high risk and at low risk for abnormal imaging. 144 00:07:56,169 --> 00:08:00,379 And both the IDSA and ESCMID guidelines for bacterial meningitis do include 145 00:08:00,379 --> 00:08:02,219 new seizures as a high risk feature. 146 00:08:02,409 --> 00:08:05,369 So this is a patient definitely we'd be considering as high risk. 147 00:08:06,830 --> 00:08:09,379 Sophie Samson: So with what we know at this time, would you recommend 148 00:08:09,390 --> 00:08:11,009 empiric antibiotic treatment? 149 00:08:12,269 --> 00:08:14,760 Kristen Bastug: I think that in order to help me answer that, it would be 150 00:08:14,760 --> 00:08:18,820 really helpful to have a, an updated understanding of her neurologic status. 151 00:08:19,200 --> 00:08:22,460 Because in a patient who's minimally responsive, I would have a lower 152 00:08:22,460 --> 00:08:26,819 threshold to start antibiotics and even acyclovir as soon as possible. 153 00:08:27,369 --> 00:08:31,805 If her symptoms have resolved and she is stable, then I think it's reasonable 154 00:08:31,925 --> 00:08:35,914 to first obtain the lumbar puncture promptly and then start the empiric 155 00:08:35,955 --> 00:08:41,385 antibiotic therapy with, um, I would choose ceftriaxone and vancomycin for her. 156 00:08:42,265 --> 00:08:46,385 Given that the meningitis encephalitis panel will result fairly quickly, 157 00:08:46,415 --> 00:08:49,845 typically within a few hours, if her clinical status is stable, 158 00:08:49,845 --> 00:08:53,245 then I would not start empiric acyclovir at this time for her. 159 00:08:54,435 --> 00:08:58,385 Finally, when considering the differential diagnosis for a seizure, we should 160 00:08:58,385 --> 00:09:01,765 also be thinking about alternative causes in case the patient doesn't 161 00:09:01,795 --> 00:09:03,615 respond to treatment as we expect. 162 00:09:04,035 --> 00:09:08,454 A focal seizure could be caused by a focal brain lesion, such as a brain tumor, which 163 00:09:08,454 --> 00:09:12,204 is another reason I favor pursuing head imaging as part of the initial workup. 164 00:09:12,824 --> 00:09:16,604 Other possibilities that are less likely at this time include autoimmune 165 00:09:16,604 --> 00:09:21,474 etiologies, such as acute disseminated encephalomyelitis, toxic substance 166 00:09:21,474 --> 00:09:23,405 ingestion, or a traumatic injury. 167 00:09:25,245 --> 00:09:28,355 Sophie Samson: A lumbar puncture was performed due to persistent headache 168 00:09:28,355 --> 00:09:32,885 that migrated to the back of her head and neck and was notable for CSF neutrophil 169 00:09:32,885 --> 00:09:37,764 predominant pleocytosis, 42 nucleated cells with the normal range being 170 00:09:38,175 --> 00:09:44,425 between 0 to 5 cells per microliter, and normal glucose and protein levels, 171 00:09:44,874 --> 00:09:50,955 and a meningitis encephalitis panel, and aerobic CSF cultures that are in process. 172 00:09:52,084 --> 00:09:54,944 MRI was performed later that day and revealed multiple 173 00:09:54,944 --> 00:09:58,244 bilateral T2 hyperintensities. 174 00:09:58,525 --> 00:10:00,825 MRA showed no vascular lesions. 175 00:10:01,364 --> 00:10:05,804 After the initial LP was performed, she was started on ceftriaxone, 100 mg 176 00:10:05,805 --> 00:10:08,314 per kg per day, divided every 12 hours. 177 00:10:08,930 --> 00:10:13,500 She had a clinical seizure captured on EEG lasting 90 seconds, and she was 178 00:10:13,500 --> 00:10:15,760 subsequently started on levetiracetam. 179 00:10:16,350 --> 00:10:20,129 She then spiked two discrete high fevers up to 104. 180 00:10:20,410 --> 00:10:25,440 2 degrees Fahrenheit, prompting a formal pediatric infectious disease consultation. 181 00:10:26,275 --> 00:10:29,615 Cultures are negative to date after 48 hours in the hospital. 182 00:10:30,355 --> 00:10:34,854 Kristen, as the ID fellow on the team with this new information, how 183 00:10:34,854 --> 00:10:36,415 does this change your differential? 184 00:10:37,664 --> 00:10:41,155 Kristen Bastug: Yeah, I'm glad we got the lumbar puncture because those results will 185 00:10:41,155 --> 00:10:43,005 really help us adjust our differential. 186 00:10:43,885 --> 00:10:49,375 So, her normal CSF glucose, normal protein, and mild to moderately elevated 187 00:10:49,375 --> 00:10:53,775 white blood cell count suggest to me that this is an aseptic meningitis, 188 00:10:53,805 --> 00:10:55,254 which would include viral processes. 189 00:10:55,255 --> 00:10:59,814 The MRI findings of multiple T2 hyperintensities also seems 190 00:10:59,815 --> 00:11:03,005 more consistent with a viral process rather than bacterial. 191 00:11:03,745 --> 00:11:07,465 The aerobic CSF cultures have been negative for 48 hours at this point 192 00:11:07,495 --> 00:11:11,704 without any antibiotic pretreatment, which further supports that a bacterial 193 00:11:11,704 --> 00:11:17,625 cause such as Staph aureus, Strep pneumoniae, or meningococcus are unlikely. 194 00:11:18,335 --> 00:11:21,835 The negative meningitis encephalitis panel offers some reassurance that this 195 00:11:21,855 --> 00:11:27,805 patient does not have HSV or enterovirus, though the sensitivity of the ME panel is 196 00:11:27,805 --> 00:11:33,405 not as high as other testing modalities, such as an HSV 1 or HSV 2 specific PCR. 197 00:11:34,175 --> 00:11:36,785 I would be interested to hear my attending's perspective on when 198 00:11:36,785 --> 00:11:40,465 we should consider ordering those additional specific PCR tests 199 00:11:40,645 --> 00:11:41,975 in addition to the ME panel. 200 00:11:42,905 --> 00:11:47,465 Finally, I note that her fever curve is uptrending to 104, though given 201 00:11:47,465 --> 00:11:51,255 that we have good evidence that this is not a bacterial process, I would not 202 00:11:51,295 --> 00:11:53,704 add any new antibiotics at this time. 203 00:11:54,315 --> 00:11:57,144 We also have good evidence this is not HSV, and so I 204 00:11:57,145 --> 00:11:59,184 would not add acyclovir either. 205 00:11:59,660 --> 00:12:03,590 What I would make sure to do is to follow her neurologic exam closely, and 206 00:12:03,590 --> 00:12:08,460 if she develops any new symptoms, such as areflexia or paralysis, then I would 207 00:12:08,460 --> 00:12:12,549 want rapid imaging of her spinal cord and a neurology consult in order to 208 00:12:12,549 --> 00:12:17,579 evaluate for inflammatory or demyelinating diseases, such as transverse myelitis. 209 00:12:17,659 --> 00:12:20,830 She should be monitored closely if those processes are suspected 210 00:12:20,890 --> 00:12:24,110 because respiratory status can rapidly decompensate in that setting. 211 00:12:25,680 --> 00:12:26,400 Beth Thielen: Thanks, Kristen. 212 00:12:26,430 --> 00:12:30,480 Yeah, I agree that at this point, 48 hours into illness, I think my suspicion 213 00:12:30,480 --> 00:12:34,829 for atypical bacterial meningitis is much, much lower and particularly 214 00:12:34,829 --> 00:12:38,759 given we have negative cultures and negative meningitis encephalitis panel 215 00:12:38,759 --> 00:12:42,929 and fevers that have persisted despite appropriately doses of ceftriaxone. 216 00:12:43,569 --> 00:12:46,720 I think at this point where I'm thinking about going is moving on to our next 217 00:12:46,720 --> 00:12:49,010 tier testing for more unusual pathogens. 218 00:12:49,500 --> 00:12:52,869 Um, but I also want to spend a couple minutes just talking about the performance 219 00:12:52,869 --> 00:12:54,900 characteristics of the testing thus far. 220 00:12:55,359 --> 00:12:59,189 And so I'm a little bit less reassured that we've adequately ruled out HSV 221 00:12:59,220 --> 00:13:03,139 when the clinical picture and in this case, new onset focal seizures would 222 00:13:03,139 --> 00:13:05,159 potentially be clinically compatible. 223 00:13:05,889 --> 00:13:09,290 And so it's well described that HSV PCR can be falsely negative, 224 00:13:09,310 --> 00:13:11,720 particularly early in the disease course. 225 00:13:12,079 --> 00:13:15,300 Um, and I think there's also, there's also been several systematic reviews 226 00:13:15,300 --> 00:13:19,084 now with increasing number of patients that have showed lower sensitivity 227 00:13:19,084 --> 00:13:21,954 of the multiplex panels for HSV. 228 00:13:21,954 --> 00:13:25,425 So I'm really thinking about wanting to repeat the LP, both for more 229 00:13:25,425 --> 00:13:29,424 specific testing for things like HSV, but also to see how the CSF 230 00:13:29,464 --> 00:13:31,284 parameters have evolved over time. 231 00:13:31,665 --> 00:13:34,824 And I think this would also have the benefit of allowing us to get additional 232 00:13:34,885 --> 00:13:38,714 specimen volume to send for that second tier testing, and oftentimes we're 233 00:13:38,714 --> 00:13:43,129 limited in terms of CSF volume for the things that we we want to test for. 234 00:13:43,129 --> 00:13:45,260 And so we have to be a little bit strategic sometimes about 235 00:13:45,260 --> 00:13:48,169 prioritizing our testing and making sure that we have enough sample 236 00:13:48,169 --> 00:13:49,760 to get those high priority tests. 237 00:13:50,229 --> 00:13:54,909 Um, in terms of specific microbes, and I'm thinking about, so I think things 238 00:13:54,909 --> 00:13:59,389 like arboviruses, LCMV, and Lyme disease or some of the pathogens that aren't 239 00:13:59,389 --> 00:14:01,319 included on those multiplex panels. 240 00:14:01,780 --> 00:14:05,444 Um, certainly respiratory viruses like flu are associated sometimes 241 00:14:05,444 --> 00:14:06,754 with neurological symptoms. 242 00:14:07,024 --> 00:14:10,244 Like in her case, we have a negative respiratory panel on admission, 243 00:14:10,254 --> 00:14:12,074 so those seem less likely. 244 00:14:12,384 --> 00:14:16,184 Um, I think I also want to ask about TB risk factors, and so that's one of the 245 00:14:16,184 --> 00:14:19,594 other, uh, you know, disease processes that wouldn't come up on routine 246 00:14:19,594 --> 00:14:24,395 testing and could present with seizures and, and a meningitis type picture. 247 00:14:27,304 --> 00:14:29,984 Sophie Samson: And a big question brought up by the neurology team was 248 00:14:29,994 --> 00:14:34,685 whether to treat with steroids or IVIG for a possible autoimmune encephalitis. 249 00:14:35,254 --> 00:14:37,304 Beth, what were the considerations there? 250 00:14:38,115 --> 00:14:41,224 Beth Thielen: Yeah, so I think I'd want to know a bit more about how 251 00:14:41,254 --> 00:14:45,385 consistent the neurology team thinks the features are with an autoimmune process. 252 00:14:45,854 --> 00:14:50,425 Um, and in this case, talking with them, I feel like they, um, were not, really 253 00:14:50,625 --> 00:14:54,405 super convinced that this is what they thought was going on and at this point, I 254 00:14:54,415 --> 00:14:58,545 don't feel like we have a clear diagnosis and so in cases like that when we have 255 00:14:58,545 --> 00:15:03,764 the two immunomodulatory therapies mentioned, I think IVIG would be the 256 00:15:03,764 --> 00:15:06,524 safer option, but it still has downsides. 257 00:15:06,914 --> 00:15:09,514 Um, so some of the infectious processes that I'm thinking about, 258 00:15:09,515 --> 00:15:14,675 maybe we may need serology to diagnose them and IVIG would impact, um, our 259 00:15:14,685 --> 00:15:16,194 ability to make those diagnoses. 260 00:15:16,685 --> 00:15:20,275 Um, furthermore, when an untreated infection is in the differential, 261 00:15:20,275 --> 00:15:22,135 I prefer to hold off on steroids. 262 00:15:22,535 --> 00:15:25,334 There's definitely some infections where steroids may make things look better 263 00:15:25,334 --> 00:15:28,954 for a while before they get worse due to the impairment to the immune control. 264 00:15:29,254 --> 00:15:31,834 And so I think if there's not a compelling reason why urgent treatment 265 00:15:31,834 --> 00:15:35,079 is needed, I would, really focus our efforts on making the diagnosis 266 00:15:35,079 --> 00:15:36,790 before we embark on a treatment. 267 00:15:38,679 --> 00:15:42,349 Kristen Bastug: Yeah, it sounds like we are in agreement that a viral process is 268 00:15:42,389 --> 00:15:46,779 at least very likely, um, and we want to recommend additional studies at this time. 269 00:15:47,200 --> 00:15:50,369 It would be helpful to also obtain additional exposure history for 270 00:15:50,369 --> 00:15:55,099 this patient, particularly outdoor exposure, travel history, animal 271 00:15:55,099 --> 00:15:56,720 exposures, and social history. 272 00:15:57,109 --> 00:15:59,174 Sophie, do you have any more of that for us? 273 00:15:59,885 --> 00:16:03,285 Sophie Samson: Yeah, um, and the neurology team doesn't feel strongly 274 00:16:03,285 --> 00:16:07,075 that this looks like an autoimmune process, but don't have any other ideas. 275 00:16:07,505 --> 00:16:10,995 They've sent autoantibodies, but these will take days to come back. 276 00:16:11,295 --> 00:16:15,964 Um, so to fill you in on some of the social history, it's currently mid July. 277 00:16:16,324 --> 00:16:18,935 The patient lives in a suburb of the Twin Cities and has been 278 00:16:18,944 --> 00:16:22,235 regularly active outside around the family's home this summer. 279 00:16:22,805 --> 00:16:24,815 The family has dogs, cats, and chickens. 280 00:16:25,365 --> 00:16:27,875 And one of the dogs had ticks earlier in the spring, but no 281 00:16:27,875 --> 00:16:29,575 ticks were found on family members. 282 00:16:29,994 --> 00:16:32,574 She did not have any rodent or bat exposures. 283 00:16:33,014 --> 00:16:36,484 Her family camped along a river five days before symptom onset. 284 00:16:37,264 --> 00:16:41,315 The patient's mom recalls that there was a transient red bump on her torso 285 00:16:41,325 --> 00:16:44,564 present at the time of her initial seizure, but has since resolved. 286 00:16:45,480 --> 00:16:47,829 She has not traveled outside of Minnesota, notably. 287 00:16:48,700 --> 00:16:52,560 How does this additional information influence the differential 288 00:16:52,560 --> 00:16:53,920 diagnosis and management? 289 00:16:54,759 --> 00:16:55,400 Kristen Bastug: Thanks, Sophie. 290 00:16:55,430 --> 00:16:56,720 That history is really helpful. 291 00:16:57,200 --> 00:17:00,250 It stands out to me that her symptoms started five days after 292 00:17:00,250 --> 00:17:01,889 the family went camping in July. 293 00:17:02,399 --> 00:17:05,210 I wonder if the skin bump that was described could be a mosquito bite. 294 00:17:05,860 --> 00:17:09,880 The outdoor exposure brings into question if her illness is potentially caused by 295 00:17:09,880 --> 00:17:13,810 a vector borne disease, which we do see more of in the summer months in Minnesota. 296 00:17:14,370 --> 00:17:17,019 There are many diseases in this category, so I'm glad that we have 297 00:17:17,020 --> 00:17:20,140 obtained her travel history to help narrow the list down a little bit. 298 00:17:20,599 --> 00:17:24,045 It sounds like she and her family have only been in in Minnesota, so I 299 00:17:24,045 --> 00:17:26,675 would start building my differential with this location in mind. 300 00:17:27,115 --> 00:17:31,274 Given that we already suspect a viral process based on her CSF results, I'm 301 00:17:31,274 --> 00:17:33,314 suspicious of an arboviral infection. 302 00:17:33,864 --> 00:17:38,255 West Nile virus, Western Equine Encephalitis, and La Crosse encephalitis 303 00:17:38,295 --> 00:17:39,965 are considered endemic to Minnesota. 304 00:17:40,514 --> 00:17:43,774 More recently, Jamestown Canyon virus is also emerging as a 305 00:17:43,774 --> 00:17:45,095 cause of disease in our state. 306 00:17:45,900 --> 00:17:49,230 Of these possibilities, La Crosse encephalitis more often affects 307 00:17:49,230 --> 00:17:50,530 children compared to adults. 308 00:17:51,130 --> 00:17:54,890 In fact, the most common arboviral cause of central nervous system 309 00:17:54,890 --> 00:17:58,240 infection in children in the United States is La Crosse virus. 310 00:17:58,639 --> 00:18:01,559 There are about 80 to 100 cases reported annually in the U. 311 00:18:01,560 --> 00:18:04,260 S., and 90 percent of those occur in children. 312 00:18:04,860 --> 00:18:08,080 This is in contrast to West Nile virus, which shows a peak incidence 313 00:18:08,080 --> 00:18:09,820 in adults over 60 years old. 314 00:18:10,695 --> 00:18:15,665 Jamestown Canyon epidemiology also indicates a lower percent of children 315 00:18:15,675 --> 00:18:17,705 with these cases, at about 7%. 316 00:18:18,665 --> 00:18:23,304 These viruses are all spread from animal reservoirs to humans through mosquitoes. 317 00:18:23,645 --> 00:18:27,004 However, we do have other important vector borne diseases in Minnesota. 318 00:18:27,624 --> 00:18:30,274 With the outdoor exposure, I think it's worth considering if there are 319 00:18:30,325 --> 00:18:32,205 other etiologies we could be missing. 320 00:18:32,675 --> 00:18:36,374 Sophie, what are some additional vector borne diseases that we could consider? 321 00:18:37,095 --> 00:18:40,405 Sophie Samson: Well, Kristen, thanks for covering viruses spread by mosquitoes 322 00:18:40,405 --> 00:18:41,715 that we think about in Minnesota. 323 00:18:42,350 --> 00:18:46,200 We also want to think about vector borne diseases spread by ticks in this area. 324 00:18:46,540 --> 00:18:50,119 This includes Lyme and other Borrelia species, Anaplasma and 325 00:18:50,120 --> 00:18:55,839 Babesia, as well as tularemia, ehrlichiosis, and Powassan virus. 326 00:18:56,299 --> 00:18:59,350 It's important to note that lacking known exposure has a low negative 327 00:18:59,389 --> 00:19:03,850 predictive value for these vector borne diseases since bites often go unnoticed. 328 00:19:04,389 --> 00:19:07,530 Knowing a patient is in a general location where they may have been 329 00:19:07,530 --> 00:19:11,139 exposed to a specific tick or mosquito is more helpful to keep in mind. 330 00:19:11,914 --> 00:19:12,554 Kristen Bastug: Thanks, Sophie. 331 00:19:13,335 --> 00:19:16,524 At this point for our patient, I think we need to obtain additional testing 332 00:19:16,524 --> 00:19:18,554 to evaluate for arboviral disease. 333 00:19:19,225 --> 00:19:22,094 I want to contact the Minnesota Department of Health at this time 334 00:19:22,094 --> 00:19:25,054 because their laboratory will be the one to process the studies. 335 00:19:25,504 --> 00:19:28,454 I often find it helpful to know ahead of time what types of specimens 336 00:19:28,455 --> 00:19:29,824 they'll require for the testing. 337 00:19:30,194 --> 00:19:33,594 Particularly for samples such as cerebrospinal fluid, I want 338 00:19:33,594 --> 00:19:36,225 to make sure that it's processed appropriately and not wasted. 339 00:19:36,815 --> 00:19:41,095 The Minnesota Department of Health requested blood, serum, and CSF samples 340 00:19:41,365 --> 00:19:43,785 for IgM antibody and RNA detection. 341 00:19:44,665 --> 00:19:49,125 They had listed some specific tests, such as an IgM for West Nile virus, 342 00:19:49,255 --> 00:19:54,544 Powassan virus, Jamestown Canyon, Western and Eastern Equine Encephalitis, 343 00:19:54,545 --> 00:19:56,715 California Group Encephalitis, and St. 344 00:19:56,715 --> 00:19:59,675 Louis encephalitis, which was ordered. 345 00:20:00,205 --> 00:20:04,665 Urine, blood, and urine RT PCR for West Nile virus was also ordered. 346 00:20:05,455 --> 00:20:09,214 Given this large panel of viruses, I'm bracing myself for the potential of 347 00:20:09,215 --> 00:20:12,764 some cross reactivity and I'll need to discuss these results carefully with my 348 00:20:12,765 --> 00:20:14,365 attending in order to interpret them. 349 00:20:14,844 --> 00:20:18,345 In the event that we had used our in house laboratory for testing, I 350 00:20:18,355 --> 00:20:21,555 think it's important for everyone to note that arbovirus disease is 351 00:20:21,555 --> 00:20:25,225 reportable, at least in Minnesota, to our state health department. 352 00:20:25,725 --> 00:20:28,225 And it has to be reported within one working day. 353 00:20:29,815 --> 00:20:33,105 Sophie Samson: A lumbar puncture was repeated for this patient due to her 354 00:20:33,105 --> 00:20:37,195 high grade fevers despite starting ceftriaxone, as well as the seizures. 355 00:20:37,754 --> 00:20:41,364 Opening pressure of the repeat lumbar puncture was 21. 356 00:20:41,405 --> 00:20:43,375 5 centimeters of water. 357 00:20:44,155 --> 00:20:50,355 CSF studies show evolution over time with an increase to 578 nucleated cells per 358 00:20:50,355 --> 00:20:56,010 microliter with 78 percent lymphocytes, stable glucose, and now protein elevation. 359 00:20:56,580 --> 00:21:00,250 Kristen, how does this new information impact your diagnostic thinking? 360 00:21:01,190 --> 00:21:03,850 Kristen Bastug: This lumbar puncture shows an increased white blood cell 361 00:21:03,850 --> 00:21:06,119 count that is predominantly lymphocytic. 362 00:21:06,460 --> 00:21:09,990 As long as her clinical status is stable, this is consistent with the evolution 363 00:21:09,990 --> 00:21:11,860 of a viral central nervous infection. 364 00:21:12,260 --> 00:21:14,630 I'm glad that we can send a CSF to the health department and 365 00:21:14,640 --> 00:21:16,290 hopefully identify the etiology. 366 00:21:17,165 --> 00:21:20,855 Sophie Samson: You mentioned that both serology and nucleic acid based testing 367 00:21:20,995 --> 00:21:22,265 was sent to the health department. 368 00:21:22,960 --> 00:21:27,100 What is the role of serology versus molecular or nucleic acid 369 00:21:27,100 --> 00:21:29,280 based tests in arboviral disease? 370 00:21:29,979 --> 00:21:33,239 Beth Thielen: Yeah, so for many arboviral infections, the period during 371 00:21:33,239 --> 00:21:36,769 which virus can be detected in any body fluid is typically quite short. 372 00:21:37,170 --> 00:21:40,500 And for this reason, PCRs can be helpful if they're positive, but 373 00:21:40,500 --> 00:21:43,280 are not necessarily sensitive enough to rule out disease. 374 00:21:43,810 --> 00:21:47,240 So our health department offers a PCR for West Nile virus, but not the 375 00:21:47,240 --> 00:21:48,990 other viruses in our differential. 376 00:21:49,040 --> 00:21:52,649 And so therefore, serological testing is the mainstay for diagnosis. 377 00:21:53,754 --> 00:21:58,485 Focusing in on those serologies, a single positive IgG is difficult to 378 00:21:58,485 --> 00:22:02,794 interpret given the relatively high risk of past undiagnosed exposure 379 00:22:02,794 --> 00:22:06,724 in our region, but a fourfold rise between an acute and a convalescent 380 00:22:06,724 --> 00:22:08,635 collected sample would be supportive. 381 00:22:09,395 --> 00:22:12,874 For this case where we're looking at acute testing, we're really looking for 382 00:22:12,875 --> 00:22:17,320 positive IgMs to indicate that acute infection, but they may be falsely 383 00:22:17,320 --> 00:22:22,530 positive in other inflammatory disorders or cross reactive against related viruses. 384 00:22:22,570 --> 00:22:26,899 And so, uh, typically a positive result in an IgM is followed up with a plaque 385 00:22:26,899 --> 00:22:31,120 reduction neutralization assay in which serial dilutions of patient serum or 386 00:22:31,120 --> 00:22:35,634 CSF are incubated with virus in vitro to determine the concentration of the virus 387 00:22:35,754 --> 00:22:39,305 at which antibodies are able to inactivate viruses such that they can no longer 388 00:22:39,305 --> 00:22:41,735 infect cells and replicate in culture. 389 00:22:42,025 --> 00:22:45,035 So in this case, higher titers would be indicate a more specific 390 00:22:45,035 --> 00:22:48,355 reaction against a particular virus and would support it being a true 391 00:22:48,365 --> 00:22:50,205 pathogen and not cross reactive. 392 00:22:50,774 --> 00:22:55,155 So such confirmatory plaque neutralization assays are really commonly used 393 00:22:55,155 --> 00:22:58,774 in arbovirology to distinguish between cross reactive viruses. 394 00:22:59,074 --> 00:23:02,365 So, examples would be the California serogroup bunyaviruses, which 395 00:23:02,365 --> 00:23:06,004 would include Jamestown Canyon virus and La Crosse virus, and then 396 00:23:06,004 --> 00:23:09,574 also the flaviviruses like West Nile, yellow fever, and dengue. 397 00:23:10,924 --> 00:23:15,704 Sophie Samson: So, for our patient, an initial screening arbovirus IgM 398 00:23:15,705 --> 00:23:24,840 IFA that tests for California group encephalitis viruses, EEEV, WEV, and SLEV 399 00:23:25,050 --> 00:23:26,850 was positive for the California group. 400 00:23:27,629 --> 00:23:34,110 Initial IgM EIA testing done at MDH on serum was positive for Jamestown 401 00:23:34,159 --> 00:23:39,080 Canyon virus, equivocal for Powassan and negative for West Nile virus. 402 00:23:40,070 --> 00:23:42,860 Serum PCR was negative for West Nile virus. 403 00:23:43,940 --> 00:23:50,179 CSF IgM EIA testing was positive for Jamestown Canyon virus and 404 00:23:50,179 --> 00:23:54,520 Powassan and negative for West Nile virus by both IgM and PCR. 405 00:23:55,300 --> 00:23:58,400 Urine PCR for West Nile virus was also negative. 406 00:23:59,225 --> 00:24:03,804 Confirmatory testing was sent to Arboviral Diseases Branch Diagnostic and Reference 407 00:24:03,804 --> 00:24:05,764 Laboratory in Fort Collins, Colorado. 408 00:24:06,265 --> 00:24:10,405 Serum testing revealed positive IgM for Jamestown Canyon Virus 409 00:24:10,645 --> 00:24:18,125 and La Crosse by IgM capture ELISA and negative for IgM for Powassan. 410 00:24:18,625 --> 00:24:25,239 La Crosse plaque reduction neutralization occurred at a greater than 1:4096 titer, 411 00:24:25,540 --> 00:24:30,010 but unfortunately there was not sufficient sample for Jamestown Canyon virus testing. 412 00:24:30,730 --> 00:24:36,180 Plaque duction, neutralization testing was also performed on CSF 413 00:24:36,450 --> 00:24:44,100 and was positive at a 1:128 titer against La Crosse, 1:4 for Jamestown 414 00:24:44,250 --> 00:24:47,199 Canyon and was negative for Powassan. 415 00:24:47,814 --> 00:24:50,655 Beth, can you discuss the interpretation of these results? 416 00:24:51,524 --> 00:24:51,925 Sure 417 00:24:52,534 --> 00:24:54,675 Beth Thielen: In this case, our initial testing was a little bit 418 00:24:54,675 --> 00:24:58,845 confusing because the results supported, uh, potential, potentially 419 00:24:58,845 --> 00:25:02,664 either or both, uh, California group encephalitis virus, of which Jamestown 420 00:25:02,665 --> 00:25:05,315 Canyon was one, uh, and Powassan. 421 00:25:05,574 --> 00:25:09,024 Uh, and there's, uh, since there was not a specific screening IgM for La 422 00:25:09,024 --> 00:25:12,475 Crosse, uh, we, we were not able to test for that and then specifically 423 00:25:12,475 --> 00:25:13,845 in the initial round of testing. 424 00:25:14,325 --> 00:25:17,635 And this is an example where the confirmatory plaque 425 00:25:17,635 --> 00:25:20,145 reduction neutralization assays were really critical. 426 00:25:20,534 --> 00:25:24,284 So the results came back with very high titers against La Crosse virus 427 00:25:24,284 --> 00:25:28,215 encephalitis pathogen with much lower titers against the Jamestown 428 00:25:28,215 --> 00:25:32,154 Canyon virus and a negative capture IgM against Powassan. 429 00:25:32,495 --> 00:25:35,875 So overall, these results were interpreted as being confirmatory 430 00:25:35,915 --> 00:25:39,844 of La Crosse virus infection being the primary pathogen in this case. 431 00:25:40,675 --> 00:25:43,075 Sophie Samson: And Beth, what do we know about the epidemiology 432 00:25:43,075 --> 00:25:44,084 of La Crosse encephalitis? 433 00:25:45,100 --> 00:25:47,770 Beth Thielen: Yeah, so this, uh, this pathogen was first described 434 00:25:47,770 --> 00:25:52,720 in the literature in 1965, uh, in a 4-year-old child from south southeastern 435 00:25:52,720 --> 00:25:56,320 Minnesota who sought care in La Crosse, Wisconsin, and ultimately died 436 00:25:56,320 --> 00:25:57,910 from an acute neurological illness. 437 00:25:57,910 --> 00:25:59,800 So that's the, hence the origin of the name. 438 00:26:00,220 --> 00:26:03,460 Um, so as, as Kristen mentioned, there's really a range of any, anywhere 439 00:26:03,460 --> 00:26:08,050 as low as 30 up to 90 or, or more, uh, cases per year of neuro invasive 440 00:26:08,050 --> 00:26:09,670 disease reported in the United States. 441 00:26:10,030 --> 00:26:12,460 Uh, and the vast, vast majority of those are among children. 442 00:26:13,070 --> 00:26:13,130 Um. 443 00:26:14,035 --> 00:26:17,875 The neurological disease is probably just the tip of the iceberg as there's 444 00:26:17,875 --> 00:26:21,595 substantial under-diagnosis and under-reporting of less severe cases. 445 00:26:22,045 --> 00:26:23,755 And so, so how do we know this? 446 00:26:23,845 --> 00:26:27,865 So there was a serological survey that was done, um, in, in a town in 447 00:26:27,865 --> 00:26:31,945 southeastern Minnesota called Winona, and they had sero positivity rates of 448 00:26:31,945 --> 00:26:34,255 up to 28% in some of the rural areas. 449 00:26:34,315 --> 00:26:37,525 So I think in places where there's the right geographic exposure in 450 00:26:37,525 --> 00:26:40,735 sort of a high risk population, like residents in a rural region, there's 451 00:26:40,735 --> 00:26:43,705 probably quite a lot of exposure on an infection that we're not - it's not, 452 00:26:43,745 --> 00:26:45,305 it's not coming to medical attention. 453 00:26:45,735 --> 00:26:49,015 Um, and so there's really a couple of pockets of this, of where this 454 00:26:49,015 --> 00:26:50,765 disease is predominantly diagnosed. 455 00:26:51,105 --> 00:26:55,545 So it's the upper Midwest, so Minnesota and Wisconsin are really high, high areas, 456 00:26:55,565 --> 00:26:57,454 and then also through, through Appalachia. 457 00:26:57,744 --> 00:27:02,044 So Ohio, Kentucky, West Virginia, North Carolina are big pockets of this disease. 458 00:27:02,765 --> 00:27:06,125 Um, it's really not clear why only a small fraction of the people who are 459 00:27:06,125 --> 00:27:08,475 exposed develop neuroinvasive disease. 460 00:27:08,745 --> 00:27:11,425 Um, And something that my lab is particularly interested in 461 00:27:11,425 --> 00:27:13,055 is, is host susceptibility. 462 00:27:13,355 --> 00:27:15,615 Um, and there's really been some interesting data that have come out 463 00:27:15,635 --> 00:27:19,295 in the last year, looking at, uh, the prevalence of auto antibodies against 464 00:27:19,305 --> 00:27:22,734 type one interferons in patients who develop neuroinvasive West Nile. 465 00:27:22,995 --> 00:27:25,784 And so I think there's more, more to come and more to learn about what, 466 00:27:25,795 --> 00:27:29,405 why it is that some people are more susceptible to these severe manifestations 467 00:27:29,405 --> 00:27:30,805 of viral pathogens than others. 468 00:27:32,315 --> 00:27:35,655 So Sophie, you had some time to interact with our health department. 469 00:27:35,975 --> 00:27:39,545 Uh, what can you tell us about what can be done to prevent lacrosse encephalitis? 470 00:27:40,155 --> 00:27:42,875 Sophie Samson: Yeah, so as the medical student on the team, I was able to 471 00:27:42,875 --> 00:27:46,915 speak with an epidemiologist on the Vector Borne Disease Unit at the 472 00:27:46,915 --> 00:27:49,864 Minnesota Department of Health and learn more about the follow up and 473 00:27:49,864 --> 00:27:51,795 prevention measures taken at this case. 474 00:27:52,495 --> 00:27:57,534 So early on, MDH involved the Metropolitan Mosquito Control District and the family 475 00:27:57,534 --> 00:27:59,405 allowed them to inspect their property. 476 00:27:59,825 --> 00:28:03,135 The initial evaluation involved removal of old tires and 477 00:28:03,135 --> 00:28:04,735 containers from the family's yard. 478 00:28:05,645 --> 00:28:10,264 The mosquito control district removed 8 tires, 4 of which had larvae, and 479 00:28:10,264 --> 00:28:12,465 32 containers, 20 of which had larvae. 480 00:28:12,895 --> 00:28:17,405 Aedes triseriatus was found in seven of the larval habitats. 481 00:28:18,035 --> 00:28:21,775 The family was educated on the importance of dumping standing water in toys and 482 00:28:21,775 --> 00:28:25,115 containers since they can serve as a breeding site for this mosquito. 483 00:28:25,884 --> 00:28:29,884 They filled one tree hole near the residence with soil, although mosquito 484 00:28:29,884 --> 00:28:32,345 larvae was absent upon further inspection. 485 00:28:33,100 --> 00:28:36,400 The Mosquito Control District also sampled adult mosquitoes and sprayed 486 00:28:36,400 --> 00:28:38,160 adulticides the following day. 487 00:28:38,740 --> 00:28:41,880 They attempted similar surveillance and control measures in the surrounding 488 00:28:41,890 --> 00:28:45,760 area and notified neighboring houses about lacrosse risk in the area. 489 00:28:46,630 --> 00:28:48,909 The neighborhood will have continued surveillance for 490 00:28:49,510 --> 00:28:53,709 several years to eliminate larvae that may carry lacrosse virus. 491 00:28:54,360 --> 00:28:57,660 MDH provided their unique perspective on the epidemiology of 492 00:28:57,670 --> 00:29:01,250 previous La Crosse cases they've been involved in and educated the 493 00:29:01,250 --> 00:29:03,060 family on mosquito bite prevention. 494 00:29:03,875 --> 00:29:08,064 Kristen, can you tell us more about standard mosquito precautions? 495 00:29:08,485 --> 00:29:09,495 Kristen Bastug: Absolutely, Sophie. 496 00:29:09,865 --> 00:29:12,715 There are several approaches to reduce the risk of mosquito bites. 497 00:29:13,004 --> 00:29:16,635 First, bug spray can be used on the skin whenever there's a risk for 498 00:29:16,635 --> 00:29:20,455 exposure to mosquitoes or ticks, particularly during the months of 499 00:29:20,475 --> 00:29:22,175 April through November in Minnesota. 500 00:29:22,915 --> 00:29:25,924 There are many products available, but you want to make sure it's a 501 00:29:25,935 --> 00:29:29,574 product registered by the Environmental Protection Agency, or the EPA. 502 00:29:30,205 --> 00:29:33,935 The most common active ingredients include DEET, picaridin, 503 00:29:34,025 --> 00:29:35,945 and oil of lemon eucalyptus. 504 00:29:36,510 --> 00:29:40,040 The American Academy of Pediatrics recommends selecting a concentration 505 00:29:40,040 --> 00:29:42,760 of DEET that matches your expected outdoor exposure time. 506 00:29:43,190 --> 00:29:46,780 For example, 10 percent DEET provides protection for about 2 507 00:29:46,810 --> 00:29:51,300 hours and 30 percent DEET provides protection for about 5 hours. 508 00:29:51,630 --> 00:29:55,540 The maximum concentration you should buy is 50 percent because anything 509 00:29:55,540 --> 00:29:59,190 beyond that does not actually provide longer protection, despite 510 00:29:59,190 --> 00:30:02,330 a potentially higher price for something that says 100 percent DEET. 511 00:30:03,440 --> 00:30:06,960 Picaridin is another active ingredient that can repel mosquitos and ticks. 512 00:30:07,360 --> 00:30:10,970 Similar to DEET, the concentration correlates with duration of protection. 513 00:30:11,529 --> 00:30:15,960 5 percent picaridin provides about 3 4 hours of protection, while 20 percent 514 00:30:15,960 --> 00:30:18,090 can provide protection for 8-12 hours. 515 00:30:19,250 --> 00:30:22,509 Oil of lemon eucalyptus is the other option I mentioned, but 516 00:30:22,510 --> 00:30:25,740 it's important to know that this is not the same as lemon oil. 517 00:30:26,170 --> 00:30:30,310 You should make sure that your OLE product is registered by the EPA and it should 518 00:30:30,310 --> 00:30:32,490 not be used in children under 3 years old. 519 00:30:33,410 --> 00:30:37,950 OLE of a concentration of 8-10 percent can protect for up to 2 520 00:30:37,950 --> 00:30:42,879 hours and 30 percent concentration, up to 40 percent concentration 521 00:30:42,879 --> 00:30:44,480 can protect for about 6 hours. 522 00:30:44,980 --> 00:30:48,860 For all of these products, it's important to read the label and avoid applying them 523 00:30:48,860 --> 00:30:52,709 directly to a child's hands because we all know that the hands are going to end 524 00:30:52,709 --> 00:30:57,050 up in the mouth and the eyes and increase risk for ingestion or eye irritation. 525 00:30:57,870 --> 00:31:01,100 When using insect repellent with sunscreen, the sunscreen 526 00:31:01,110 --> 00:31:02,330 should be applied first. 527 00:31:03,200 --> 00:31:07,770 Other than topical bug spray, you can also choose to wear long sleeve clothing and 528 00:31:07,770 --> 00:31:09,380 pre treat the clothing with permethrin. 529 00:31:09,850 --> 00:31:12,620 You could also choose to avoid areas with dense vegetation. 530 00:31:12,980 --> 00:31:16,159 Finally, mosquito nets are a great option and you can pre treat 531 00:31:16,159 --> 00:31:17,739 those with an insecticide as well. 532 00:31:18,270 --> 00:31:22,820 So for our patient, it sounds like Sophie, you had some excellent communication with 533 00:31:22,830 --> 00:31:26,470 the Department of Health and they worked with the family to talk about prevention. 534 00:31:27,260 --> 00:31:30,769 What did you learn from talking to the family or from MDH about 535 00:31:30,970 --> 00:31:33,600 how the child's doing now and what the future might look like? 536 00:31:34,010 --> 00:31:36,860 Sophie Samson: Well, when I was able to speak with the family, they updated 537 00:31:36,860 --> 00:31:41,740 me on her six week follow up after discharge and shared that at that time 538 00:31:41,740 --> 00:31:45,749 she was having headaches about every two weeks, but she has had no new seizures. 539 00:31:46,210 --> 00:31:48,939 She's doing well in school and remains social and active with 540 00:31:48,949 --> 00:31:51,900 some activity modification to follow seizure precautions, 541 00:31:52,440 --> 00:31:54,949 but overall is doing excellent. 542 00:31:55,695 --> 00:32:01,205 Repeat brain imaging, um, both MRI and EEG done at the follow up 543 00:32:01,265 --> 00:32:03,225 showed resolution of prior lesions. 544 00:32:03,734 --> 00:32:07,894 She's tapering off levetiracetam and will continue to follow up with neurology. 545 00:32:08,595 --> 00:32:12,545 The parents shared that while seeing their daughter so sick and having seizures was 546 00:32:12,545 --> 00:32:16,225 incredibly scary, they felt supported by all the teams involved in her care, 547 00:32:16,495 --> 00:32:19,625 and they're happy to see her back on track and doing the things she enjoys. 548 00:32:22,080 --> 00:32:24,530 Sara Dong: Thanks again to Sophie, Kristen, and Beth 549 00:32:24,540 --> 00:32:26,120 for joining Febrile today. 550 00:32:26,590 --> 00:32:29,200 Febrile is produced with support from the Infectious Diseases 551 00:32:29,210 --> 00:32:31,100 Society of America, or IDSA. 552 00:32:31,400 --> 00:32:34,010 Don't forget to check out the website, febrilepodcast. 553 00:32:34,010 --> 00:32:38,020 com, where you can find the Consult Notes, which are written complements 554 00:32:38,020 --> 00:32:42,039 of the show with links to references, our library of ID infographics, 555 00:32:42,590 --> 00:32:43,930 and a link to our merch store. 556 00:32:44,080 --> 00:32:45,000 Thanks for listening. 557 00:32:45,030 --> 00:32:46,590 Stay safe and we'll see you next time.