1 00:00:08,460 --> 00:00:09,360 Sara Dong: Hi everyone. 2 00:00:09,420 --> 00:00:13,380 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:13,740 --> 00:00:19,320 We use consult questions to dive into ID clinical reasoning, diagnostics, and antimicrobial management. 4 00:00:19,530 --> 00:00:22,290 I'm Sara Dong, your host and Med-Peds ID fellow. 5 00:00:22,470 --> 00:00:29,095 Here on Febrile, we use patient cases and chat with ID discussants to learn more about high yield ID topics. 6 00:00:29,155 --> 00:00:30,565 I am joined today by Dr. 7 00:00:30,565 --> 00:00:31,595 Kruti Yagnik. 8 00:00:31,745 --> 00:00:38,995 Kruti is the ID staff physician and co-director of antibiotic stewardship at Cleveland Clinic Florida Indian River Hospital. 9 00:00:39,085 --> 00:00:49,964 She completed her ID fellowship at UT Southwestern Medical Center, her internship and residency at the University of Florida, and her med school education at Nova Southeastern University. 10 00:00:50,505 --> 00:00:57,525 She has a particular interest in general ID, HIV and opportunistic infections and antibiotic stewardship. 11 00:00:57,765 --> 00:00:58,815 Welcome to the show. 12 00:00:58,935 --> 00:00:59,665 Kruti Yagnik: Hi Sara. 13 00:00:59,685 --> 00:01:00,045 Thanks so 14 00:01:00,045 --> 00:01:00,735 much for having me. 15 00:01:00,740 --> 00:01:01,935 I'm so excited to be here. 16 00:01:02,205 --> 00:01:07,544 Sara Dong: Uh, so before we get started, we, like to pride ourselves as everyone's favorite culture podcast. 17 00:01:07,994 --> 00:01:12,304 So I'd love to hear a little piece of culture or, you know, something that you like to do outside of work. 18 00:01:12,630 --> 00:01:16,229 Kruti Yagnik: So I am like a big fan of movies and TV shows. 19 00:01:16,259 --> 00:01:17,549 And I would say, 20 00:01:17,639 --> 00:01:17,699 Sara Dong: yeah, 21 00:01:17,699 --> 00:01:21,389 Kruti Yagnik: probably my top favorite shows are probably like Schitts Creek. 22 00:01:21,449 --> 00:01:22,499 Um, obviously 23 00:01:22,499 --> 00:01:22,949 Sara Dong: it's so good 24 00:01:22,949 --> 00:01:26,579 Kruti Yagnik: medical, so scrubs, um, Breaking Bad. 25 00:01:26,999 --> 00:01:29,429 Stranger Things, season four was pretty sweet, 26 00:01:29,789 --> 00:01:30,475 Sara Dong: so good 27 00:01:30,475 --> 00:01:33,660 Kruti Yagnik: I know it was like, I can't believe have to wait so long for the next one. 28 00:01:34,410 --> 00:01:34,829 Sara Dong: I know. 29 00:01:35,489 --> 00:01:37,559 Kruti Yagnik: And then probably Game of Thrones. 30 00:01:37,589 --> 00:01:39,299 Um, and the Marvelous Mrs. 31 00:01:39,299 --> 00:01:41,679 Maisal are probably like my top favorite shows. 32 00:01:41,899 --> 00:01:43,009 Sara Dong: Yeah, I love it so much. 33 00:01:43,249 --> 00:01:43,549 Yeah. 34 00:01:43,549 --> 00:01:46,940 That's the only thing about these amazing high quality television shows. 35 00:01:46,940 --> 00:01:49,490 Now you have to wait so much longer between seasons. 36 00:01:49,490 --> 00:01:54,619 Kruti Yagnik: I know it's like just that countdown that you have, that you have to just wait for that, that next season to come on. 37 00:01:54,619 --> 00:01:54,979 But. 38 00:01:55,560 --> 00:01:57,210 Yeah, it makes it worth it, I guess. 39 00:01:58,260 --> 00:01:58,740 Sara Dong: Yeah. 40 00:01:58,830 --> 00:02:07,350 And so if listeners had not already noticed, this summer, I've had a few, uh, fever in a returning traveler episodes, and we're gonna keep the theme going today. 41 00:02:07,470 --> 00:02:15,659 I really thought this would be a nice introduction because new fellows are getting settled in, but also we're finally seeing people travel a lot more this summer. 42 00:02:16,110 --> 00:02:18,990 I, I guess if their flights aren't canceled, they're traveling. 43 00:02:19,529 --> 00:02:25,140 Um, and so I wanted us to have a couple episodes that focused on things that we might see more commonly. 44 00:02:25,170 --> 00:02:27,329 So if people listen to the last two episodes. 45 00:02:27,420 --> 00:02:30,959 Um, but today we're actually gonna talk about an interesting case that you saw on fellowship. 46 00:02:31,050 --> 00:02:37,800 And I'm not gonna give any spoilers yet, but we thought we would just start with a kind of a review and a reminder. 47 00:02:38,175 --> 00:02:41,265 Reemphasizing what we've talked about in some of the prior episodes. 48 00:02:41,295 --> 00:02:47,055 And that would be how to evaluate these patients who come in with a fever that have recently traveled somewhere. 49 00:02:47,535 --> 00:02:55,695 And from a history standpoint, we talk a lot about symptoms and really the time period of those symptoms. 50 00:02:55,700 --> 00:03:02,330 How important that timeline and comparing it to incubation periods is, and then certainly all the other things we like to know. 51 00:03:03,075 --> 00:03:04,815 What did you do while you were traveling? 52 00:03:04,815 --> 00:03:07,395 Were you spelunking, were you swimming? 53 00:03:08,115 --> 00:03:10,155 Were you around animals, insects. 54 00:03:10,275 --> 00:03:23,205 Um, and then we certainly talk about food and water consumption and then something that we also have emphasized is vaccinations and whether or not patients have had some sort of chemoprophylaxis provided before their trip. 55 00:03:23,385 --> 00:03:27,315 And so a couple of our last guests have included places. 56 00:03:28,110 --> 00:03:32,070 Or references that they point learners to when they're encountering these cases. 57 00:03:32,070 --> 00:03:41,020 I thought I would start by asking if you had a favorite thing that you like to mention to everyone and any other sort of special pearls when approaching these patients. 58 00:03:41,200 --> 00:03:42,070 Kruti Yagnik: Yeah, absolutely. 59 00:03:42,070 --> 00:03:55,790 So I think as you mentioned, history is so important, especially in the infectious disease world and a lot of things you can just find out by just talking to your patients and getting a better idea of what exactly they did when they were traveling, who they were around. 60 00:03:56,380 --> 00:04:01,090 You know, if animal exposures, activities, I think all those things are really, really important. 61 00:04:01,360 --> 00:04:08,290 And then of course, if these people did get their pre travel vaccinations or prophylaxis, cause that makes a huge difference. 62 00:04:08,590 --> 00:04:12,820 One of the websites that I really like is the CDC Travelers Health website. 63 00:04:13,480 --> 00:04:20,890 What's really great about it is if you go to that website and you actually can, can click down to exactly which country they may have traveled to. 64 00:04:21,190 --> 00:04:30,700 And it tells you based on that country, kind of the risk factors of what they may be exposed to, and then the recommendations on if they need certain types of vaccinations or prophylaxis. 65 00:04:31,120 --> 00:04:35,290 So I think that's a great start to look for kind of exposure risk by country. 66 00:04:35,590 --> 00:04:37,510 And I know we will include that. 67 00:04:38,735 --> 00:04:51,010 and I think another important thing is always kind of when you get a patient like this, that comes through your ER or to your hospital, and you get that call as that fellow on call that night, you should always ask yourself, does this patient need isolation? 68 00:04:51,010 --> 00:04:52,030 Because that's huge. 69 00:04:52,360 --> 00:05:00,490 And we always have to consider things like Ebola, severe respiratory viruses, diarrhea illnesses, and things that can actually be contagious to other patients. 70 00:05:00,940 --> 00:05:12,835 So the way I approach this is if you don't know what this patient has yet, but it sounds contagious or it sounds like it's something severe, always when in doubt, just place them in isolation until you can see them. 71 00:05:12,895 --> 00:05:19,555 You know, if it's an overnight call until you see them the next morning, until you can get some more lab work back, until you can rule out a couple things. 72 00:05:19,825 --> 00:05:22,825 It's better to kind of are on that side of caution and put them in isolation. 73 00:05:23,575 --> 00:05:30,820 and I know we already kind of talked a little bit about it, but you know, don't ever forget that you have to rule out malaria cuz malaria is an infectious disease emergency. 74 00:05:31,330 --> 00:05:31,630 Sara Dong: Yeah. 75 00:05:32,080 --> 00:05:32,260 Yeah. 76 00:05:32,265 --> 00:05:38,560 I feel like all the lists that you have for fever and returning traveler probably should have malaria one through like 10. 77 00:05:38,620 --> 00:05:39,400 Kruti Yagnik: Absolutely. 78 00:05:39,460 --> 00:05:40,780 Sara Dong: And then add on everything else. 79 00:05:40,780 --> 00:05:41,770 Kruti Yagnik: Always, always 80 00:05:41,830 --> 00:05:44,570 Sara Dong: um, Uh, great. 81 00:05:44,660 --> 00:05:50,780 So we're gonna jump to the case and today's consult question, not surprisingly is fever in a returning traveler. 82 00:05:50,840 --> 00:06:00,680 So we have a 51 year old man with a history of hypertension who presented for evaluation of fevers, confusion, lethargy, and a 35 pound weight loss. 83 00:06:00,710 --> 00:06:05,240 And so he had been confused at home and had some difficulty with word finding. 84 00:06:05,300 --> 00:06:13,175 His sister is with him and reports that he had been completely well or at his baseline until about five months prior to presentation. 85 00:06:13,235 --> 00:06:21,695 And then the family had started to notice generalized weakness, confusion, and then really progression to what was more of somnolence. 86 00:06:21,745 --> 00:06:24,409 Around this time he started to have fevers and weight loss. 87 00:06:24,440 --> 00:06:31,969 He did not have any other associated symptoms, such as headache, cough, dyspnea, rash, joint pain, or diarrhea. 88 00:06:32,060 --> 00:06:35,840 And so for a little background about the patient, he was born in Cameroon. 89 00:06:36,119 --> 00:06:42,900 Attended college in Nigeria and then returned to Cameroon to work as a missionary and a theological professor. 90 00:06:42,969 --> 00:06:45,159 He has a pretty extensive travel history. 91 00:06:45,669 --> 00:06:53,520 Um, back in 2001, he had traveled to Mali, Senegal, Algeria, and Guinea, um, immigrated to the US. 92 00:06:54,080 --> 00:06:57,229 And then has had a couple trips since living in the US. 93 00:06:57,320 --> 00:07:10,480 So in 2013, he traveled to several countries, including back to Cameroon, Nigeria, South Africa, Ghana, the Central African Republic, and many other non-African countries. 94 00:07:10,930 --> 00:07:13,870 His last trip to Cameroon was in 2017. 95 00:07:13,990 --> 00:07:22,300 Um, and then in November of 2018, he did have a trip in Ghana where he spent some time outdoors and mentions that he had an insect bite on his thigh. 96 00:07:22,300 --> 00:07:25,330 That was a little bit red, a little bit painful. 97 00:07:25,390 --> 00:07:32,260 Uh, he did have some weakness and fatigue around this time, which was similar to a prior episode of malaria. 98 00:07:32,460 --> 00:07:33,780 This improved though. 99 00:07:33,840 --> 00:07:41,910 He had been doing a little bit better, but then in May of 2019, he developed fever, night sweats, and weight loss. 100 00:07:42,000 --> 00:07:47,989 Uh, he had been traveling at the time, continued traveling, visited Jerusalem in June of 2019. 101 00:07:47,989 --> 00:07:57,099 So about a month into these, uh, newer symptoms and he had a syncopal event requiring hospitalization, but we don't really have any other details available to us. 102 00:07:57,250 --> 00:08:01,310 He is back in the US as of July of 2019. 103 00:08:01,370 --> 00:08:06,229 And when he got back, he went to a local hospital for fever, weight loss, and this weakness. 104 00:08:06,260 --> 00:08:11,599 He had a CT scan of his chest, abdomen and pelvis, which showed diffuse lymphadenopathy. 105 00:08:12,080 --> 00:08:19,634 And ultimately had a supraclavicular lymph node biopsy, but the results were benign, didn't show any evidence on malignancy. 106 00:08:19,724 --> 00:08:24,344 And so the patient was discharged home without really a clear diagnosis of what was going on. 107 00:08:24,344 --> 00:08:29,474 And unfortunately his symptoms progressed to the point where he was having nightly fevers. 108 00:08:29,565 --> 00:08:32,625 And this sort of ties us back to where we were talking earlier. 109 00:08:32,625 --> 00:08:35,194 He had been increasingly confused and weak. 110 00:08:35,774 --> 00:08:40,164 He has stopped working completely and actually has been using a wheelchair to get around. 111 00:08:40,194 --> 00:08:44,795 He came to your hospital with this confusion, weakness, and now somnolence. 112 00:08:44,815 --> 00:08:50,375 When you meet him on exam, he is cachetic, he is febrile and tachycardic. 113 00:08:50,545 --> 00:08:53,365 He has no evidence of lymph adenopathy at this point. 114 00:08:53,454 --> 00:08:58,885 And his cardiac, respiratory, abdominal and skin exams were normal. 115 00:08:59,420 --> 00:09:03,949 And then on neurology exam, I mentioned he was, uh, slow to respond. 116 00:09:04,100 --> 00:09:09,620 We have all this information about his travel, thankfully with a lot of details right now, and then these symptoms. 117 00:09:09,650 --> 00:09:11,660 So what are you thinking about at this point? 118 00:09:11,660 --> 00:09:13,460 How are you gonna approach this case? 119 00:09:13,850 --> 00:09:21,770 Kruti Yagnik: Yeah, so, I mean, just to kind of summarize this, we have this elderly gentleman, um, with an extensive travel history, he's kind of traveled all over the world. 120 00:09:21,770 --> 00:09:23,150 This is what he does for work. 121 00:09:23,689 --> 00:09:32,959 And he's presenting with fevers, weight loss, confusion and just progressively worsening neurological symptoms to the point that he's now somnolent. 122 00:09:33,910 --> 00:09:44,680 Over in this case, I think the most important thing is his travel history is extremely important because he's been to so many places and you have to really think about where he's been and what could he have been exposed to. 123 00:09:45,130 --> 00:09:52,420 So by looking at his travel history, I think that that could definitely shorten our differential because the places that he's been to would point us to certain things. 124 00:09:53,249 --> 00:09:57,219 and then you also have to think about which infections are most prevalent in those countries. 125 00:09:57,699 --> 00:10:03,219 So the way I kind of approach this is that, you know, this case would be a typical case of kind of fever of unknown origin. 126 00:10:03,459 --> 00:10:19,899 So this person has had fevers for many weeks now, has had a little bit of a workup, with no answer at this point and kind of going back to kind of what we think of when a patient comes in with fever of unknown origin, the most common causes are usually infectious, rheumatologic, or malignancy. 127 00:10:20,349 --> 00:10:24,760 So, you know, you have to definitely think about all those things and roll these things out in these patients. 128 00:10:25,240 --> 00:10:40,180 So our initial differential here is, you know, obviously we considered rheumatologic and malignancy and we did run, um, certain autoimmune tests, ANA, things to look for lupus, Sjogrens disease, um, some other things. 129 00:10:40,180 --> 00:10:58,555 And then our initial infectious differential was along the lines of tuberculosis, HIV, obviously, malaria, african trypanosomiasis, other endemic fungal infections, and then just other vector born infections, just because he had recalled that insect bite that he had in the past. 130 00:10:59,185 --> 00:11:03,024 So what we do at this point is, you know, we develop a differential in our mind. 131 00:11:03,029 --> 00:11:06,954 We say based on where he's been, these are the things he could have been exposed to. 132 00:11:07,045 --> 00:11:08,514 These are the things that he might have. 133 00:11:08,904 --> 00:11:09,954 So where do we go next? 134 00:11:09,954 --> 00:11:13,644 And you always wanna start with kind of a basic initial workup. 135 00:11:14,185 --> 00:11:17,814 So that usually considers into fact things like basic labs. 136 00:11:17,814 --> 00:11:23,694 So obviously check blood counts, check kidney function, liver function, CBC, CMP. 137 00:11:24,275 --> 00:11:26,994 To rule out malaria, you always have to check those blood smears. 138 00:11:27,504 --> 00:11:32,664 And then based on kind of what symptoms they have, you wanna go a little bit further and you can consider imaging. 139 00:11:33,144 --> 00:11:37,675 You know, if patients came in with respiratory symptoms, you would do a chest x-ray or a CT scan of the chest. 140 00:11:38,419 --> 00:11:41,454 and you always wanna kind of start there and go further. 141 00:11:41,454 --> 00:11:49,014 If they're having urinary symptoms, you can check a urinalysis, check a urine culture, check blood cultures, kind of start with your basic infectious workup. 142 00:11:49,554 --> 00:11:57,114 And then if they're having diarrhea symptoms, you can check a stool culture, stool ova parasites, if they had exposure in other countries. 143 00:11:57,564 --> 00:12:04,254 And then if you are concerned about things like dengue, Zika, chikungunya then you can check viral serologies. 144 00:12:05,109 --> 00:12:13,869 Patients that always travel to other countries, there's always a risk of hepatitis A, you can do hepatitis testing and then also get further imaging based on their symptoms. 145 00:12:14,379 --> 00:12:25,709 So in this patient's case, you know, one of his main concerning symptoms was his confusion, his lethargy, his somnolence, you know, obviously we were concerned that something was going on neurologically. 146 00:12:26,214 --> 00:12:31,134 So in his case, we did definitely get a CT scan, CT of the head, an MRI of the brain. 147 00:12:31,434 --> 00:12:35,614 And we got a lumbar puncture because, you know, we have to rule out neurological things in this patient. 148 00:12:36,094 --> 00:12:38,934 Sara Dong: Yeah, I'll update everyone on our results. 149 00:12:39,174 --> 00:12:42,474 We had our CBC and our chemistries, which were normal. 150 00:12:42,504 --> 00:12:47,400 We had some of the autoimmune rheumatologic screens that you mentioned that were unrevealing. 151 00:12:47,430 --> 00:12:57,750 His CT chest abdomen pelvis showed some scattered bilateral axillary and inguinal lymph nodes, largest at about a centimeter in size. 152 00:12:57,870 --> 00:13:02,910 And then we had mentioned those lymph node biopsies from our prior admission, which were negative for malignancy. 153 00:13:03,164 --> 00:13:08,489 And comparing the images there wasn't something that stood out as new or concerning for malignancy. 154 00:13:08,609 --> 00:13:13,109 And then as you mentioned, from a ID standpoint, the workup was quite broad. 155 00:13:13,109 --> 00:13:16,290 We had blood cultures, we had peripheral blood smears. 156 00:13:16,349 --> 00:13:23,670 We had, uh, MTB interferon gamma release, assay, syphilis screening, E BV and CMV blood PCR. 157 00:13:24,000 --> 00:13:35,339 We have urine Histoplasma antigen, endemic fungal antibody tests, so including Blasto[myces] and Coccioidio[ides] and then serum beta D-glucan and Cryptococcal antigen. 158 00:13:35,400 --> 00:13:40,860 We had Ricketssia antibodies, West Nile virus testing, and a Lyme antibody. 159 00:13:40,920 --> 00:13:44,119 All of which, everything I just mentioned were negative. 160 00:13:44,179 --> 00:13:52,729 There was a HIV test that had a indeterminate HIV-2 antibody result, but confirmatory testing confirmed this as a false positive. 161 00:13:52,879 --> 00:13:55,129 Um, he also had a CD4 count, which was normal. 162 00:13:55,180 --> 00:13:58,020 We have the MRI and CT of the brain, which was normal. 163 00:13:58,479 --> 00:14:06,969 His LP was done, at this point, we're sort of on the second day of admission and the cerebral spinal fluid shows 638 nucleated cells. 164 00:14:06,999 --> 00:14:09,249 And on that diff, a hundred percent lymphocytes. 165 00:14:09,339 --> 00:14:12,310 The cytology did not show any malignant cells. 166 00:14:12,729 --> 00:14:22,865 And then we'll sort of fast forward and already let you know that the CSF testing for arboviruses, VDRL, HSV, VZV and Enterovirus are all negative. 167 00:14:22,895 --> 00:14:30,844 So we've done all these tests and unfortunately we don't have a definitive answer here, but the patient continues to have some intermittent fevers. 168 00:14:30,905 --> 00:14:37,459 Initially it was about daily and now is starting to space out, but still persistent, at least every couple days. 169 00:14:37,519 --> 00:14:41,839 And his somnolence seems to be worsening despite broad spectrum antimicrobial. 170 00:14:41,839 --> 00:14:48,049 So vancomycin, ceftriaxone, piperacillin-tazobactam, acyclovir and doxycyclin. 171 00:14:48,079 --> 00:14:49,609 So what's your next step here? 172 00:14:49,609 --> 00:14:51,169 What do you think we might be missing? 173 00:14:51,679 --> 00:14:52,009 Kruti Yagnik: Yeah. 174 00:14:52,009 --> 00:14:53,419 So this is definitely a tough case. 175 00:14:53,419 --> 00:14:57,319 You know, we've kind of looked at malignancy, we've looked at rheumatological things. 176 00:14:57,649 --> 00:15:03,259 We've done a huge infectious workup on, on things that we would expect something to have come up positive. 177 00:15:03,259 --> 00:15:04,759 And so far we didn't see anything. 178 00:15:05,354 --> 00:15:09,525 So we're kind of in a position where everything was negative, but the patient continued to worsen. 179 00:15:09,525 --> 00:15:12,015 And, you know, we put him on broad spectrum antibiotics. 180 00:15:12,015 --> 00:15:13,995 He was on antivirals with acyclovir. 181 00:15:13,995 --> 00:15:17,354 He was on doxycyclin for tickborne illnesses. 182 00:15:17,895 --> 00:15:21,015 And we thought at this point, you know, we really need to broaden our workup. 183 00:15:21,314 --> 00:15:24,675 So we looked at some of the not so common causes of the patient's symptoms. 184 00:15:25,035 --> 00:15:33,435 The main thing that we were really edging on here was his extensive travel history, you know, that did put him at risk for many infections that we don't typically see in the United States. 185 00:15:33,975 --> 00:15:35,835 And then kind of looking at his lumbar puncture. 186 00:15:35,835 --> 00:15:38,475 This was the interesting part because it was definitely not normal. 187 00:15:38,475 --> 00:15:43,035 He had 638 nucleated cells with a hundred percent lymphocyte predominance. 188 00:15:43,215 --> 00:15:44,954 So there was definitely some inflammation there. 189 00:15:45,405 --> 00:15:49,985 And we were kind of wondering where to go from here because all of his CSF studies were negative. 190 00:15:50,615 --> 00:15:57,375 We decided at that point, you know, he was having these fevers, he's having weight loss and he's having scattered lymphadenopathy. 191 00:15:57,860 --> 00:16:00,410 He had negative biopsies of his lymph nodes. 192 00:16:00,410 --> 00:16:04,610 So at this point we said, why don't we get a bone marrow biopsy and see what's going on there? 193 00:16:04,969 --> 00:16:05,360 Sara Dong: Yeah. 194 00:16:05,420 --> 00:16:09,290 And as we always say, a diagnostic test was performed. 195 00:16:09,319 --> 00:16:17,900 So the bone marrow aspirate, which at this point was about day 10 of admission, revealed normal cellular marrow with necrotizing granulomatous inflammation. 196 00:16:18,410 --> 00:16:25,610 The fungal and acid fast bacilli stains were negative, but we do get some information that reveals our answer. 197 00:16:26,449 --> 00:16:36,729 Two trypanosomes were identified on the marrow aspirate smear by the ID pathologist and microbiologist, and the morphology was consistent with Trypanosoma brucei. 198 00:16:37,189 --> 00:16:41,530 So here we have a final diagnosis of human African trypanosomiasis! 199 00:16:41,530 --> 00:16:46,670 Also known as African sleeping sickness, um, something that we definitely don't see commonly. 200 00:16:46,670 --> 00:16:51,560 So can you tell us about what you learned about human African trypanosomiasis with this case? 201 00:16:51,560 --> 00:16:52,189 Kruti Yagnik: Absolutely. 202 00:16:52,189 --> 00:16:52,839 I'd love to. 203 00:16:52,889 --> 00:16:59,789 So this was an incredibly fascinating case because it's something that I feel like most of us have never seen and may not ever see. 204 00:17:00,209 --> 00:17:10,860 And I just wanna give like a huge thank you to our amazing pathologist that we had because they did such an amazing job looking at that slide to be able to identify those trypanosomes. 205 00:17:11,219 --> 00:17:14,969 Um, and we actually had them go back a couple of times and look at his CSF. 206 00:17:15,299 --> 00:17:20,549 , we were telling them about this patient and saying, you know, we don't know what's going on, and they spent a lot of time being very thorough. 207 00:17:20,549 --> 00:17:25,739 So if it wasn't for the extensive evaluation they did, we may have never made this diagnosis. 208 00:17:26,189 --> 00:17:29,729 Human African trypanosomiasis is known as African sleeping sickness. 209 00:17:29,879 --> 00:17:33,899 And it's an infectious disease that's endemic to Sub-Saharan Africa. 210 00:17:34,649 --> 00:17:41,639 It's caused by the parasite Trypanosoma brucei, which is transmitted by a tsetse fly, which is the Glossina genus. 211 00:17:42,470 --> 00:17:51,955 And most people that are exposed to the tsetse fly and to the disease usually live in rural areas and they depend on agriculture, fishing and animal husbandry and hunting. 212 00:17:52,014 --> 00:17:56,065 So there are two forms of the disease that are caused by a different subspecies. 213 00:17:56,395 --> 00:18:01,525 You have T.brucei gambiense, which is endemic to West and Central Africa. 214 00:18:01,975 --> 00:18:04,765 And this is usually kind of a slowly progressive disease. 215 00:18:05,155 --> 00:18:08,515 This is the one that's most prevalent, about 95% of cases. 216 00:18:09,175 --> 00:18:14,905 These patients can be infected for kind of many months or years without any major signs of symptoms. 217 00:18:15,264 --> 00:18:21,114 And then when they finally have symptoms, they're usually pretty far advanced with CNS findings. 218 00:18:21,114 --> 00:18:26,304 So that's when you talk about things like the lethargy, the somnolence, um, all those neurological issues. 219 00:18:26,935 --> 00:18:31,945 And then you have T.brucei rhodesiense, which is, is endemic in Eastern and Southern Africa. 220 00:18:32,424 --> 00:18:35,904 This is more of an acute illness that kind of comes on over a span of weeks. 221 00:18:35,904 --> 00:18:42,384 So, you know, when you're thinking about this, you have to really distinguish between the two, because the way they present is extremely different. 222 00:18:42,985 --> 00:18:47,874 And the most important thing about this is that this disease is considered fatal if it's left untreated. 223 00:18:48,024 --> 00:18:50,194 The disease usually goes through kind of two different stages. 224 00:18:51,144 --> 00:18:59,604 You have a hemo lymphatic stage, which is when it's in the blood followed by a meningoencephalitic stage when they actually cross the blood brain barrier. 225 00:19:00,145 --> 00:19:16,315 And then once the parasites go into the blood brain barrier, you get these typical neurological symptoms like our patient had, which consists of things like mental confusion, abnormal behavior, tremors, weakness, issues with speech, they can even have seizures. 226 00:19:16,615 --> 00:19:20,215 And then eventually this does progress to somnolence , which is what happened to our patient. 227 00:19:21,235 --> 00:19:32,125 So transmission is usually through the tsetse fly bite, but it can also be including things like mechanical transmission, accidental in the lab, and also sexual contact. 228 00:19:32,754 --> 00:19:34,645 Our patient had an extensive travel history. 229 00:19:34,645 --> 00:19:48,315 He had been ill for several months, but at that time, you know, human African trypanosomiasis was considered unlikely just because it's, it's pretty rare for us to see it here, but he did report travel to only urban areas in both Ghana and Cameroon. 230 00:19:48,675 --> 00:19:55,545 So that was another thing that, where we thought, you know, he was in only in these urban areas and this is usually more prevalent in the rural areas. 231 00:19:55,545 --> 00:19:57,915 So that's why we didn't really think that it was possible. 232 00:19:58,335 --> 00:20:04,695 And you know, there's been a lot of reports saying that in those urban areas, HAT maybe eliminated. 233 00:20:04,695 --> 00:20:09,615 What was really interesting in this case is because it was such a complex travel history and there was so much involved. 234 00:20:09,975 --> 00:20:12,115 We did report this case to the WHO. 235 00:20:12,915 --> 00:20:17,235 And the patient reported travel to only urban areas in Ghana and Cameroon. 236 00:20:17,805 --> 00:20:29,115 But we were told that the distinction between the urban and the rural areas in Mamfe, Cameroon, which is where he, where went, was kind of blurred and there has been recorded transmission in the periurban areas. 237 00:20:29,295 --> 00:20:39,929 So we were told that it was possible that he may have acquired this infection when he was in Mamfe, Cameroon, where, you know, even though he was in an, um, an urban area, He may have still caught it there. 238 00:20:40,139 --> 00:20:44,850 What's really interesting here is that this is a very, very rare diagnosis in returning travelers. 239 00:20:45,360 --> 00:20:55,379 There's something called a Geosentinel Surveillance Network, which kind of monitors returning travelers and Trypanosoma brucei gambiense, human African trypanosomiasis, is very rare. 240 00:20:55,754 --> 00:21:02,715 There was only a single case reported amongst over 42,000 ill returning travelers between 2007 and 2011. 241 00:21:03,135 --> 00:21:05,625 So that tells you that this is not something that we see very often. 242 00:21:06,044 --> 00:21:06,435 Sara Dong: Yeah. 243 00:21:06,435 --> 00:21:17,340 And something I learned when reviewing this is that Uganda is the only location that potentially would have both forms of disease, although they're sort of in separate zones. 244 00:21:17,399 --> 00:21:18,659 Um, and so we'll put a link. 245 00:21:18,659 --> 00:21:21,149 I think a really good reference is the WHO fact sheet. 246 00:21:21,149 --> 00:21:24,305 So if people want a good summary of the highlights. 247 00:21:24,305 --> 00:21:25,595 That's a great place to go. 248 00:21:25,775 --> 00:21:27,035 I think the next question is. 249 00:21:27,995 --> 00:21:30,965 Let's say we were more concerned about this early on. 250 00:21:30,995 --> 00:21:35,914 Are there other diagnostics that we could have used if we were highly suspicious of this? 251 00:21:36,394 --> 00:21:37,264 Kruti Yagnik: Yeah, absolutely. 252 00:21:37,264 --> 00:21:43,504 So usually definitive diagnosis relies on microscopic visualization of parasite, which is what we did in our case. 253 00:21:43,509 --> 00:21:47,014 Uh, we actually were able to see the parasite on that bone marrow smear. 254 00:21:47,044 --> 00:21:53,084 However, there is a card agglutination test for trypanosomiasis it's called a CATT. 255 00:21:53,779 --> 00:21:55,370 It's very fast and sensitive. 256 00:21:55,429 --> 00:22:01,009 And it screens for Trypanosoma brucei gambiense antibodies in blood, plasma, or serum. 257 00:22:01,489 --> 00:22:05,179 There's also a PCR test in the blood, which is very sensitive and specific. 258 00:22:05,689 --> 00:22:13,279 Serological and PCR tests are unfortunately not available in the United States, but they can be performed at several reference labs outside the US. 259 00:22:13,279 --> 00:22:24,665 So we actually did have to send our samples to a couple of reference labs, not in the United States to confirm our diagnosis because although we did visualize the parasite on smear, we did wanna confirm it before we started appropriate treatment. 260 00:22:25,409 --> 00:22:30,084 There's, there's a couple different ways that you can look at it, but usually have a multidisciplinary approach to get it done. 261 00:22:30,564 --> 00:22:30,895 Sara Dong: Yeah. 262 00:22:30,895 --> 00:22:41,354 And I was, I was gonna say that's a perfect transition, cuz I think we're gonna finish up and talk a little bit about treatment and what are the options available if we have the unlikely chance that we see a patient with this? 263 00:22:41,414 --> 00:22:42,314 Kruti Yagnik: Yeah, of course. 264 00:22:42,314 --> 00:22:50,334 So, uh, the diagnosis and treatment for this case was done in collaboration with the CDC Division for Parasitic Diseases and Malaria and the WHO. 265 00:22:50,669 --> 00:22:55,320 So they helped us with sending out the samples, confirming the diagnosis, and obtaining the treatment. 266 00:22:55,949 --> 00:23:03,259 So there's actually been significant progress made in the development of new oral agents, capable of curing both stages of gambiense HAT. 267 00:23:04,350 --> 00:23:10,210 And we actually followed the WHO guidelines for treatment of severe disease with nifurtimox-eflornithine. 268 00:23:10,919 --> 00:23:21,409 And what was interesting is this was actually the first time that that combination therapy N E CT was used for treatment of meningoencephalitc stage of T brucei gambiense HAT in the United States. 269 00:23:21,789 --> 00:23:28,500 So we had to coordinate with the CDC and we used an investigational new drug application to obtain those medications and to give it to our patient. 270 00:23:28,560 --> 00:23:32,530 Sara Dong: Well, this is, this is such an awesome case and this was published in OFID. 271 00:23:32,554 --> 00:23:41,040 So for, uh, anyone who's listening that wants to read a little bit more or check out some of the images and figures that came with that we'll have a link, but most importantly, how did the patient do? 272 00:23:41,189 --> 00:23:43,350 Kruti Yagnik: Yeah, so very exciting news. 273 00:23:43,350 --> 00:23:45,540 He did great pretty much, you know, he had. 274 00:23:46,040 --> 00:23:48,320 Having these symptoms for months, not doing well. 275 00:23:48,649 --> 00:23:53,479 And then as soon as we gave him the medications in about four days, his mental status significantly improved. 276 00:23:53,870 --> 00:24:04,340 He obviously did require, um, some time in rehab, but he was discharged from the hospital about a month after he was admitted, fully recovered, had some time in rehab and then was discharged home. 277 00:24:04,870 --> 00:24:11,149 And, you know, I think last time we had spoken with him during a couple follow ups, he was back to working and pretty much back to his baseline. 278 00:24:11,149 --> 00:24:14,729 So just amazing how quickly he got better after getting the medication. 279 00:24:15,194 --> 00:24:23,084 And I just wanted to also put out there that I really appreciated all the work of my co-authors, who were really, you know, instrumental in every part of this case. 280 00:24:23,144 --> 00:24:35,894 Um, all of the faculty at UT Southwestern, you know, even though not everybody was able to be published on the case, we had so many people that we were running this case by people that were giving us advice, helping us with testing, just people to bounce ideas off of. 281 00:24:35,894 --> 00:24:38,414 And they were all just amazing in helping us with this. 282 00:24:38,745 --> 00:24:44,594 And then obviously also thank the CDC and the WHO who were all integral in diagnosis and treating this patient. 283 00:24:45,224 --> 00:24:51,104 And, you know, what's important is in then the last 20 years, there's been a lot of concerted efforts diagnosed, treat and eliminate this. 284 00:24:52,079 --> 00:24:57,659 And the World Health Organization has actually targeted the interruption of transmission of this by 2030. 285 00:24:57,779 --> 00:24:58,169 Sara Dong: Yeah. 286 00:24:58,169 --> 00:25:06,659 Well, this is a really interesting zebra case really meant to complement the prior episodes, which focus on what we're gonna see much more commonly. 287 00:25:06,689 --> 00:25:16,219 But I think this is also a really great example of the amazing multidisciplinary teams that we often get to be a part of and, and really to learn from in ID. 288 00:25:16,435 --> 00:25:16,915 All right. 289 00:25:16,915 --> 00:25:21,834 Well, I leave a little space at the end to see if you have any closing thoughts for our listeners. 290 00:25:22,195 --> 00:25:23,905 Kruti Yagnik: Yeah, no, I mean, thank you so much for having me. 291 00:25:23,905 --> 00:25:25,165 This has been really awesome. 292 00:25:25,165 --> 00:25:28,044 This was just such a great case and I just love sharing it with people. 293 00:25:28,584 --> 00:25:34,105 And I think again, just, you know, as, as ID doctors and in what we do, the main thing is. 294 00:25:34,659 --> 00:25:38,290 Always get a good history, trust your instincts, you know, ask around. 295 00:25:38,439 --> 00:25:50,820 Um, that was one of the things that we did where, you know, when we hit a couple roadblocks or we just didn't know where to go with this, you know, we talked to other people in our group, we, you know, called people and other departments, utilized the people around you. 296 00:25:51,509 --> 00:25:55,559 If you don't have an answer yet, keep looking because you will find one as ID doctors. 297 00:25:55,559 --> 00:25:58,679 I know we always keep looking, but I think that's the most important thing. 298 00:25:59,219 --> 00:25:59,309 Yeah. 299 00:25:59,309 --> 00:26:02,489 And always kind of keep an open mind and keep reading. 300 00:26:02,669 --> 00:26:04,679 Um, and I think that's kind of the most important stuff here. 301 00:26:05,099 --> 00:26:05,279 Sara Dong: Yeah. 302 00:26:05,519 --> 00:26:06,539 Well, I love it. 303 00:26:06,839 --> 00:26:09,599 Well, thank you so much for coming on and sharing your case. 304 00:26:10,259 --> 00:26:11,099 Kruti Yagnik: Thanks for having me. 305 00:26:11,519 --> 00:26:17,099 Sara Dong: If you haven't already, please be sure to check out the last two episodes, which also tackle fever and returning travel. 306 00:26:17,459 --> 00:26:28,080 You can also check out our website febrilepodcast.com to find the Consult Notes, which are written complements of the show with links to references, our library of ID infographics, and a link to our merch store. 307 00:26:28,320 --> 00:26:32,850 Please reach out if you have any suggestions for future shows or wanna be more involved with Febrile. 308 00:26:33,209 --> 00:26:33,989 Thanks for listening. 309 00:26:33,989 --> 00:26:35,639 Stay safe, and I'll see you next time.