1 00:00:05,197 --> 00:00:06,037 Hi everyone. 2 00:00:06,067 --> 00:00:10,327 Welcome to Febrile, a cultured podcast about all things infectious disease. 3 00:00:10,717 --> 00:00:14,527 We use consult questions to dive into ID clinical reasoning, diagnostics 4 00:00:14,527 --> 00:00:15,787 and antimicrobial management. 5 00:00:15,984 --> 00:00:18,834 I'm Sara Dong, your host and a Med Peds ID doc. 6 00:00:19,055 --> 00:00:23,945 Today we are joined by a team from Sultan Qaboos University in Muscat, Oman. 7 00:00:24,185 --> 00:00:28,535 First up, I'll introduce Dr. Raghad Al-abdwani, who is a Senior 8 00:00:28,535 --> 00:00:31,595 Consultant and the Head of the Pediatric Intensive Care Unit. 9 00:00:32,081 --> 00:00:33,261 Hi, it's Raghad. 10 00:00:33,281 --> 00:00:35,266 Thank you very much for having us here today. 11 00:00:35,680 --> 00:00:39,990 Next we have Dr. Badriya Al Adawi, who is a medical microbiologist. 12 00:00:40,359 --> 00:00:44,344 Hi, this is Badriya, thank you for having us today. 13 00:00:44,410 --> 00:00:47,540 And rounding out our team, we have Dr. Zaid Al Hinai. 14 00:00:47,737 --> 00:00:50,917 Zaid serves currently as the Head of the Pediatric ID Unit 15 00:00:50,917 --> 00:00:52,147 at the Child Health Department. 16 00:00:52,422 --> 00:00:53,022 This is Zaid. 17 00:00:53,292 --> 00:00:54,642 Thank you for hosting us. 18 00:00:54,824 --> 00:00:55,334 All right. 19 00:00:55,334 --> 00:01:00,194 So as everyone's favorite cultured podcast, we always like to start by 20 00:01:00,194 --> 00:01:04,424 asking if folks would share a little piece of culture, really just something 21 00:01:04,429 --> 00:01:06,854 non-medical that brings you happiness. 22 00:01:07,064 --> 00:01:12,594 So I have a particular knack or interest in hiking, trekking, abseiling. 23 00:01:12,614 --> 00:01:16,634 And though I've done a number of international tracks, like, uh, Machu 24 00:01:16,634 --> 00:01:21,884 Picchu, Kilimanjaro, Everest Base Camp, but, Oman itself offers a lot of really 25 00:01:21,884 --> 00:01:26,524 beautiful mountains and caves and a number of very challenging canyons. 26 00:01:27,029 --> 00:01:32,069 So sometimes people ask me like, don't you get enough adrenaline, uh, in the PICU? 27 00:01:32,729 --> 00:01:36,029 But I always say to them that the adrenaline in these 28 00:01:36,029 --> 00:01:37,619 adventures are quite different. 29 00:01:37,619 --> 00:01:41,969 And I see it as a way to help in like, um, you know, pressing the reset button. 30 00:01:42,119 --> 00:01:42,629 Love it. 31 00:01:42,839 --> 00:01:47,399 I don't know, I feel like the, um, the extreme hiking and PICU in 32 00:01:47,399 --> 00:01:49,049 my mind goes together perfectly. 33 00:01:49,514 --> 00:01:49,934 It does. 34 00:01:49,934 --> 00:01:52,754 It kind, it balances each other how I see it. 35 00:01:55,165 --> 00:02:02,865 Um, so for me, I enjoy going back to my hometown Nizwa and, uh, a few 36 00:02:02,865 --> 00:02:08,615 months ago, I went with my kids and we went to the fort, the Fort of Nizwa. 37 00:02:09,700 --> 00:02:11,410 And it was an amazing feeling. 38 00:02:11,410 --> 00:02:16,540 I haven't been there for a very long time, so just walking around with 39 00:02:16,540 --> 00:02:21,670 my kids, it was just like, really, I cannot describe the feeling. 40 00:02:21,670 --> 00:02:26,765 It felt like I went into a time machine with my kids and went, went to the past. 41 00:02:28,185 --> 00:02:30,310 So it was really, really great. 42 00:02:30,434 --> 00:02:31,214 That's lovely. 43 00:02:32,249 --> 00:02:32,469 Mm. 44 00:02:32,469 --> 00:02:32,829 Okay. 45 00:02:32,889 --> 00:02:36,729 Uh, for me, actually, one thing that's really nice about living 46 00:02:36,729 --> 00:02:38,949 in the Middle East is the food. 47 00:02:39,639 --> 00:02:44,379 There is like this really ancient recipes that have been perfected 48 00:02:44,439 --> 00:02:46,359 over like thousands of years. 49 00:02:46,839 --> 00:02:51,729 And so, uh, I really enjoy learning some of these really old recipes. 50 00:02:51,729 --> 00:02:54,519 Like ones my grandmother would, would have made. 51 00:02:55,009 --> 00:02:59,289 I did learn, actually, one of the Middle Eastern recipes is a Palestinian 52 00:02:59,289 --> 00:03:01,659 recipe called, uh, musakhan. 53 00:03:02,219 --> 00:03:06,109 Musakhan in Arabic just means something that's warmed up or cooked. 54 00:03:06,349 --> 00:03:12,574 This one is really uniquely Palestinian and it's got this, uh, unique 55 00:03:12,574 --> 00:03:14,494 ingredients, onions and chicken. 56 00:03:14,524 --> 00:03:18,824 Not, not very unique, but then they put sumac, which is a very, 57 00:03:18,824 --> 00:03:24,874 uh, unique Middle Eastern, like, kind of, uh, tangy, a sour spice. 58 00:03:25,294 --> 00:03:28,594 And, uh, I, I learned how to make it, and they make it usually with bread. 59 00:03:29,074 --> 00:03:32,164 And knowing me, like I always like to put a twist on things. 60 00:03:32,164 --> 00:03:35,704 So what I did is I made it in a pie. 61 00:03:36,034 --> 00:03:41,674 And that's from my years in America, put all this chicken into 62 00:03:41,674 --> 00:03:44,119 a pie and it came out really good. 63 00:03:44,239 --> 00:03:46,659 I had good beginners luck on that. 64 00:03:46,809 --> 00:03:50,369 You're going to have to share that with us Zaid! 65 00:03:50,704 --> 00:03:51,724 that sounds really good. 66 00:03:55,594 --> 00:04:00,559 Well, I think I've, I think I've told people on the podcast before, but, um, I 67 00:04:00,559 --> 00:04:03,389 love cooking and learning about cooking. 68 00:04:03,389 --> 00:04:07,049 And I originally wanted to find some way to tie it in where people 69 00:04:07,049 --> 00:04:10,169 brought a recipe or a dish that they like to just talk about. 70 00:04:10,649 --> 00:04:13,529 Um, but I couldn't find something clever to tie them together. 71 00:04:13,529 --> 00:04:17,689 But I still have a special place in my heart for when people bring recipe or 72 00:04:17,689 --> 00:04:20,719 food related things as their culture. 73 00:04:21,664 --> 00:04:24,694 Well, we have a very interesting case today. 74 00:04:24,694 --> 00:04:28,594 I think Raghad is gonna, um, introduce us to the patient 75 00:04:28,594 --> 00:04:29,794 who's shown up in the hospital. 76 00:04:29,899 --> 00:04:34,849 Yeah, so we started off with a PICU team visiting the emergency department. 77 00:04:34,849 --> 00:04:39,499 Uh, we went to see a 4-year-old boy with sickle cell disease, Hemoglobin 78 00:04:39,499 --> 00:04:44,764 SS, on hydroxyurea and he had presented to the emergency department with a five 79 00:04:44,764 --> 00:04:49,444 day history of fever and fatigue, which was just getting worse over the days. 80 00:04:49,444 --> 00:04:52,804 He even then started having significant abdominal pain. 81 00:04:53,104 --> 00:04:56,974 He vomited a couple of times and he was looking quite pale to the parents. 82 00:04:57,329 --> 00:05:00,419 And even had a yellowish discoloration as they described. 83 00:05:00,959 --> 00:05:04,469 So they took him to the local health center just a day prior to 84 00:05:04,469 --> 00:05:08,249 presenting to us, and they did a CBC at that time, which showed that the 85 00:05:08,249 --> 00:05:11,399 hemoglobin was 5.4 grams per deciliter. 86 00:05:11,729 --> 00:05:15,329 So basically much lower than his baseline, which is about eight 87 00:05:15,329 --> 00:05:17,049 or nine grams per deciliter. 88 00:05:18,244 --> 00:05:22,144 So in the emergency department, um, the child appeared quite pale. 89 00:05:22,174 --> 00:05:24,034 He was jaundiced and drowsy. 90 00:05:24,364 --> 00:05:28,324 He was quite tachycardic with heart rates in the 160s, tachypneic and 91 00:05:28,324 --> 00:05:32,464 desaturating with sats of 85% in room air. 92 00:05:32,764 --> 00:05:36,454 But with giving him supplemental oxygen, it was above 95%. 93 00:05:37,114 --> 00:05:40,724 What was striking is that he was extremely cold to touch and he had 94 00:05:40,764 --> 00:05:45,964 poor peripheral pulses and delayed capillary refill of about five seconds, 95 00:05:46,294 --> 00:05:51,314 but his blood pressure was actually normal, normal high, even 120/70. 96 00:05:52,054 --> 00:05:56,104 So when examined his chest, he had a hyperdynamic precordium and he 97 00:05:56,104 --> 00:05:59,854 had an ejection systolic murmur at the apex, but good air entry 98 00:05:59,854 --> 00:06:01,504 bilaterally with no added sounds. 99 00:06:02,469 --> 00:06:06,729 His abdomen was very, very distended and it revealed also a very 100 00:06:06,729 --> 00:06:12,079 tender big liver, palpable at 15 centimeters below the costal margin. 101 00:06:12,319 --> 00:06:15,019 But we couldn't palpate, uh, spleen, which is, you know, what 102 00:06:15,019 --> 00:06:16,879 we tend to see in those patients. 103 00:06:17,419 --> 00:06:22,159 Um, he was drowsy and irritable, but he didn't have any meningeal signs and he 104 00:06:22,159 --> 00:06:25,039 had no apparent focal neurologic deficits. 105 00:06:25,609 --> 00:06:29,869 We examined his ears, his nose, and his throat, and they were unremarkable. 106 00:06:30,884 --> 00:06:34,754 Now in the emergency department, we have access to a blood gas machine. 107 00:06:34,754 --> 00:06:39,104 So we did a venous blood gas, which showed that he had severe anemia 108 00:06:39,134 --> 00:06:44,714 with a hemoglobin of 2.3, and he had severe lactic metabolic acidosis. 109 00:06:44,714 --> 00:06:46,964 So his pH was 7.05. 110 00:06:47,384 --> 00:06:52,454 His bicarb was seven with a base deficit of 15, and his lactate 111 00:06:52,454 --> 00:06:54,324 was 22 milli moles per liter. 112 00:06:55,379 --> 00:06:59,489 So taking all that into consideration our impressions that we've got a 4-year-old 113 00:06:59,489 --> 00:07:04,619 boy with sickle cell disease and he had shock and take into consideration that 114 00:07:04,619 --> 00:07:08,459 these kids are prone to encapsulated organisms, and the fever, you know, 115 00:07:08,459 --> 00:07:12,579 we thought along the lines of septic shock, and likely a sequestration 116 00:07:12,579 --> 00:07:17,499 because of the severe anemia plus minus a sickle cell, uh, crisis. 117 00:07:17,649 --> 00:07:21,674 And of course, we were yet to look for evidence of multi-organ dysfunction. 118 00:07:23,239 --> 00:07:25,459 So just a little about his past medical history. 119 00:07:25,459 --> 00:07:29,839 As I mentioned, his sickle cell disease, and he had history of previous 120 00:07:29,839 --> 00:07:34,189 admissions because of vaso-occlusive crises and needs for blood transfusion. 121 00:07:34,579 --> 00:07:38,869 But in the past, one year after starting hydroxyurea, the frequency 122 00:07:38,869 --> 00:07:40,879 of his admissions were much less. 123 00:07:41,869 --> 00:07:47,269 So Zaid, now with all the above, are there any other additional information that 124 00:07:47,269 --> 00:07:48,859 you'd like to know about the patient? 125 00:07:49,332 --> 00:07:49,722 Yeah. 126 00:07:49,752 --> 00:07:54,372 So it sounds like the child is in the critical condition, septic shock. 127 00:07:54,402 --> 00:07:56,532 There's some liver involvement. 128 00:07:56,962 --> 00:08:02,212 You guys did a great job to look at a lot of the uh, systems that could be involved. 129 00:08:02,662 --> 00:08:07,282 Uh, we also would like to know a little bit if there's any skin manifestations 130 00:08:07,282 --> 00:08:09,502 or joint manifestations in this child. 131 00:08:09,982 --> 00:08:13,012 Uh, from the ID point of view, we always like to ask about 132 00:08:13,012 --> 00:08:15,052 exposure history, very important. 133 00:08:15,052 --> 00:08:17,012 So, where does he live? 134 00:08:17,042 --> 00:08:18,302 What kind of setting? 135 00:08:18,352 --> 00:08:22,672 Was there anybody sick that he could have uh, been in contact with? 136 00:08:23,072 --> 00:08:24,662 Did he travel anywhere? 137 00:08:24,962 --> 00:08:26,642 Uh, does he, do they have any pets? 138 00:08:26,642 --> 00:08:28,982 Do they, uh, go to any farms? 139 00:08:29,042 --> 00:08:30,992 Is there any other animal exposure? 140 00:08:30,992 --> 00:08:35,102 Do they consume un pasteurized dairy products or undercooked meat? 141 00:08:35,632 --> 00:08:38,842 Is there anybody with tuberculosis potentially? 142 00:08:39,182 --> 00:08:44,302 And did he have any insect bites or tick bites or mosquito bites? 143 00:08:44,382 --> 00:08:46,872 And did he go swimming anywhere? 144 00:08:46,872 --> 00:08:47,967 What is the water source? 145 00:08:48,667 --> 00:08:48,947 Mm-hmm. 146 00:08:49,792 --> 00:08:52,552 So, you know, it's interesting you mentioned that 'cause we did notice 147 00:08:52,552 --> 00:08:56,512 at that time that, you know, he had these multiple round hyper pigment, 148 00:08:56,512 --> 00:09:01,822 hyperpigmented macular rashes of about, I would say, two to three centimeters in 149 00:09:01,822 --> 00:09:06,022 diameter in his upper, but especially in his lower extremities, especially like in 150 00:09:06,022 --> 00:09:09,112 the pretibial, the bony prominences areas. 151 00:09:09,382 --> 00:09:13,072 But, you know, uh, taking the nature of his dark skin, it was really hard to tell 152 00:09:13,072 --> 00:09:18,442 that time if these were bruises or there were insect, uh, like healing insect bites 153 00:09:18,442 --> 00:09:20,812 or maybe a rash of a different etiology. 154 00:09:21,112 --> 00:09:25,232 It's not unusual that we see these dark pigmented, uh, spots in kids, 155 00:09:25,232 --> 00:09:27,062 generally speaking here with dark skin. 156 00:09:27,392 --> 00:09:30,772 But his joint examination was otherwise unremarkable. 157 00:09:31,342 --> 00:09:36,652 But in terms of exposures, um, he does live in a rural area of Oman 158 00:09:36,682 --> 00:09:38,932 in a house with a nearby farm. 159 00:09:38,932 --> 00:09:43,462 But the parents, uh, upon asking them, had mentioned that they couldn't 160 00:09:43,462 --> 00:09:48,022 remember any history of contacts with any animals or cattle or birds, 161 00:09:48,292 --> 00:09:51,952 but they did say that he does get occasional ticks or mosquito bites. 162 00:09:52,372 --> 00:09:56,442 Um, nothing about unpasteurized products that they had taken. 163 00:09:56,802 --> 00:10:01,212 Um, and water source, they usually have like drink from bottles, bottled water. 164 00:10:01,692 --> 00:10:04,782 Um, and there was no history of any recent travel. 165 00:10:05,292 --> 00:10:07,362 His immunization was up to date. 166 00:10:07,362 --> 00:10:10,062 The thing is, we, as you know, we have a really good immunization 167 00:10:10,062 --> 00:10:15,102 program in Oman, and locals tend to really adhere to it, uh, fortunately. 168 00:10:15,602 --> 00:10:19,622 In terms of family history, I would say that, um, there wasn't anything 169 00:10:19,622 --> 00:10:22,982 that was really remarkable except from another, another family member 170 00:10:22,982 --> 00:10:24,752 who also has sickle cell disease. 171 00:10:26,327 --> 00:10:31,097 And in terms of the immunizations, did he get any of those special immunizations 172 00:10:31,097 --> 00:10:34,367 additionally for sickle cell disease, like the pneumococcal vaccine? 173 00:10:35,057 --> 00:10:35,477 Yes. 174 00:10:35,477 --> 00:10:39,317 So, I mean, you know, again, it's integrated as part of what 175 00:10:39,317 --> 00:10:40,907 we have in the health centers. 176 00:10:41,207 --> 00:10:44,447 Um, I'm really proud actually, of our immunization program here. 177 00:10:44,447 --> 00:10:46,127 So yes, he, he, he did. 178 00:10:46,992 --> 00:10:51,372 Um, so Zaid, I mean, take into consideration, you know, that impression 179 00:10:51,372 --> 00:10:55,892 of the septic shock and all this history into account, what infections do you think 180 00:10:55,897 --> 00:10:58,127 would be, uh, a likely cause over here? 181 00:11:00,382 --> 00:11:02,392 I mean, this child is coming in very sick. 182 00:11:02,662 --> 00:11:04,282 He's coming in from the community. 183 00:11:04,672 --> 00:11:07,347 Uh, he's been progressively sick over five days. 184 00:11:08,137 --> 00:11:10,507 You have to think about common things being common. 185 00:11:10,957 --> 00:11:16,172 Um, as you mentioned, they can be susceptible to Streptococcus pneumonia, 186 00:11:16,562 --> 00:11:20,762 um, and salmonella in particular with, with sickle cell disease. 187 00:11:21,062 --> 00:11:24,302 So those would be pretty high on the differential as far as septicemia. 188 00:11:24,802 --> 00:11:29,632 Additionally, other organisms like Staph aureus, Haemophilus influenzae, 189 00:11:29,912 --> 00:11:31,672 Neisseria, should be in consideration. 190 00:11:32,047 --> 00:11:36,307 Cholecystitis can happen in sickle cell disease and maybe that 191 00:11:36,307 --> 00:11:42,097 can, uh, perhaps, uh, predispose to septicemia and bacteremia. 192 00:11:42,607 --> 00:11:46,667 I think although it's, it's looking more like a very acute maybe 193 00:11:46,667 --> 00:11:51,137 bacterial infection, they probably could be a respiratory virus 194 00:11:51,137 --> 00:11:55,457 involved, especially some viruses that have, uh, tropism to the liver. 195 00:11:55,547 --> 00:11:59,417 Since the liver here is uniquely addedly involved. 196 00:11:59,417 --> 00:12:07,007 So I would think about Enteroviruses, adenovirus, influenza, COVID, uh, EBV, 197 00:12:07,187 --> 00:12:12,272 uh, maybe some other herpes viruses, although we don't see specific, uh, 198 00:12:12,302 --> 00:12:16,802 vesicular skin manifestations, like for varicella or herpes simplex? 199 00:12:17,342 --> 00:12:20,712 I think the hepatitis viruses definitely would think about, at 200 00:12:20,712 --> 00:12:26,472 that time that this child presented the Hepatitis A, uh, vaccine hadn't 201 00:12:26,472 --> 00:12:29,082 yet been in the schedule, it is now. 202 00:12:29,532 --> 00:12:32,622 Um, so that was something that we would see from time to time. 203 00:12:33,102 --> 00:12:37,572 Never discount something like HIV as being maybe potentially 204 00:12:37,572 --> 00:12:39,492 part of this, or, or dengue. 205 00:12:39,767 --> 00:12:42,432 And dengue also is mosquito-borne illness. 206 00:12:42,432 --> 00:12:44,412 There's a history here of insect bites. 207 00:12:44,882 --> 00:12:49,952 And at that time, again, dengue was not an issue in, in, in Oman, but now has become 208 00:12:49,952 --> 00:12:52,262 endemic, so now we have to think about it. 209 00:12:53,122 --> 00:12:56,032 So those would be, I think, the most common places to start. 210 00:12:56,032 --> 00:13:00,172 You always have to keep an open mind though for other things, 211 00:13:00,172 --> 00:13:04,252 potentially fungal, although I can't think of much there, maybe 212 00:13:04,252 --> 00:13:07,882 histoplasmosis or uh, atypical bacteria. 213 00:13:07,882 --> 00:13:12,362 Mycoplasma does tend to cause more significant disease and sickle cell 214 00:13:12,362 --> 00:13:16,862 disease and other rickettsia, Brucella, Q fever, tularemia leishmania. 215 00:13:18,272 --> 00:13:21,782 Uh, mycobacterial, TB, parasitic, malaria. 216 00:13:22,172 --> 00:13:25,802 Um, malaria would be, I think, an important differential, although we 217 00:13:25,802 --> 00:13:30,372 don't have much local transmission at all in Oman, usually always, 218 00:13:30,432 --> 00:13:31,872 uh, associated with travel. 219 00:13:31,872 --> 00:13:34,522 But, it can also be always a consideration. 220 00:13:34,982 --> 00:13:39,722 So, uh, besides that, maybe after infection, you, you should think about 221 00:13:39,722 --> 00:13:46,592 maybe some autoimmune diseases, uh uh, or, uh, maybe could this be an unusual 222 00:13:46,592 --> 00:13:49,232 presentation of MIS-C or Kawasaki? 223 00:13:49,562 --> 00:13:51,737 But I think those are less likely possibilities. 224 00:13:53,087 --> 00:13:53,477 Right? 225 00:13:53,477 --> 00:13:53,777 Yes. 226 00:13:53,777 --> 00:13:54,227 Thank you. 227 00:13:54,737 --> 00:13:57,587 So, you know, at that point of time in the emergency department, 228 00:13:57,587 --> 00:13:59,567 we immediately started management. 229 00:13:59,567 --> 00:14:04,667 So, you know, your usual ABCs, oxygen therapy, we gave him a small fluid bolus. 230 00:14:04,697 --> 00:14:07,847 Not too much because we don't want him to go into heart failure when 231 00:14:07,847 --> 00:14:09,617 his hemoglobin is already 2.3. 232 00:14:10,007 --> 00:14:13,877 Um, we started him with small aliquots of blood transfusions. 233 00:14:13,877 --> 00:14:18,257 He got three small aliquots of packed red blood cells and again, small 234 00:14:18,347 --> 00:14:20,647 and slow to avoid heart failure. 235 00:14:21,007 --> 00:14:24,517 Uh, we ended up intubating him, uh, with mechanical ventilation, taking to 236 00:14:24,517 --> 00:14:28,867 consideration, you know, his shocked state, uh, severe lactic acidosis. 237 00:14:29,077 --> 00:14:33,137 His abdomen was quite distended, so, you know, compressing on his lungs. 238 00:14:33,557 --> 00:14:36,947 Um, and also he was in a lot of pain and needed narcotics. 239 00:14:36,947 --> 00:14:38,747 So, you know, that would make him even drowsier. 240 00:14:39,347 --> 00:14:40,697 So he was intubated. 241 00:14:40,747 --> 00:14:44,377 We sent off all the routine labs as well as, you know, those looking for 242 00:14:44,377 --> 00:14:48,787 multiorgan dysfunction, but also, those needed for looking for sepsis, 243 00:14:48,787 --> 00:14:50,977 inflammatory markers, cultures. 244 00:14:51,222 --> 00:14:54,732 Blood, urine, tracheal secretions, you know, taking the fact 245 00:14:54,732 --> 00:14:58,482 that he was initially, um, tachypneic and desaturating. 246 00:14:58,722 --> 00:15:03,012 We sent off the respiratory viral panel, mycoplasma PCR, in some 247 00:15:03,012 --> 00:15:04,542 serologies, as you'd mentioned. 248 00:15:04,542 --> 00:15:09,342 EBV, CMV, HIV, and hepatitis especially because he was jaundiced 249 00:15:09,342 --> 00:15:11,772 and had a tender large liver. 250 00:15:12,202 --> 00:15:17,872 Of course it was started on broad spectrum antimicrobials, so cefotaxime, vancomycin, 251 00:15:17,872 --> 00:15:20,392 and a, a dose of amikacin as well. 252 00:15:21,052 --> 00:15:24,202 And that's when we started getting the lab results back. 253 00:15:24,622 --> 00:15:29,752 Um, his, uh, CBC showed again, confirmed the hemoglobin of 2.3 with 254 00:15:29,752 --> 00:15:32,122 a reticulocytes percentage of 4%. 255 00:15:32,422 --> 00:15:35,632 Um, he had some leukocytosis of 18.6. 256 00:15:36,552 --> 00:15:42,102 Of which 34% were neutrophils, and he was thrombocytopenic, 73,000. 257 00:15:42,492 --> 00:15:47,022 His CRP was quite elevated at almost 350, and his liver 258 00:15:47,352 --> 00:15:49,122 transaminases were quite high. 259 00:15:49,182 --> 00:15:53,052 Um, his ALT was almost a thousand units per liter and 260 00:15:53,052 --> 00:15:56,257 AST was 4,200 right off the bat. 261 00:15:56,767 --> 00:15:59,267 Um, he had hyperbilirubinemia. 262 00:15:59,287 --> 00:16:05,017 Most of it was direct, some hypoalbuminemia 37, not too, too bad. 263 00:16:05,377 --> 00:16:07,087 And he had some coagulopathy. 264 00:16:07,087 --> 00:16:12,397 His INR was 1.6 with D Dimers of 12.9, but his electrolytes and 265 00:16:12,397 --> 00:16:13,507 renal parameters were normal. 266 00:16:14,372 --> 00:16:19,652 His chest x-ray was unremarkable and his abdominal x-ray didn't show any evidence 267 00:16:19,682 --> 00:16:22,952 of perforation or intestinal obstruction. 268 00:16:22,952 --> 00:16:26,067 You know, take into consideration that significant abdominal pain that he had. 269 00:16:27,177 --> 00:16:30,807 So we did a quick bedside echo and it showed that ejection 270 00:16:30,807 --> 00:16:34,957 fraction was about 50%, so, you know, the lower side of normal. 271 00:16:35,827 --> 00:16:39,667 So taking all the above, our findings confirmed that, you know, 272 00:16:39,667 --> 00:16:43,987 our initial thought that this is severe anemia, septic shock. 273 00:16:44,317 --> 00:16:48,487 Um, and he had what, like it looked like hepatic sequestration 274 00:16:48,817 --> 00:16:50,797 with some multiorgan dysfunction. 275 00:16:50,797 --> 00:16:55,082 And we took him for a quick CT, which which actually confirmed the 276 00:16:55,082 --> 00:16:57,242 evidence of hepatic sequestration. 277 00:16:58,867 --> 00:17:02,257 So, um, we took him to the ICU after that. 278 00:17:02,767 --> 00:17:07,117 We worked really hard on him for the first couple of days, and then the next like 279 00:17:07,117 --> 00:17:13,237 24 to 36 hours, you know, by then we had raised his hemoglobin to his baseline. 280 00:17:13,537 --> 00:17:17,467 He, after topping him up, we gave him an exchange transfusion as well to make 281 00:17:17,467 --> 00:17:19,447 sure his hemoglobin S levels were okay. 282 00:17:20,217 --> 00:17:22,887 We made sure he was well volume repleted. 283 00:17:22,947 --> 00:17:25,737 He was already on broad spectrum antimicrobials. 284 00:17:26,097 --> 00:17:29,127 He was on a good amount of sedatives, analgesics. 285 00:17:29,127 --> 00:17:34,437 He was supported with a ventilator and his blood gas is even normalized, but 286 00:17:34,437 --> 00:17:38,757 something was off because we noticed that at that time he was still really, really 287 00:17:38,787 --> 00:17:41,697 tachycardic even when he was afebrile. 288 00:17:42,167 --> 00:17:46,577 And he was still quite vaso constricted and really cold to touch. 289 00:17:46,907 --> 00:17:50,597 And we even started him on milrinone, which is, uh, as intensivist. 290 00:17:50,597 --> 00:17:52,327 We call it an inodilator. 291 00:17:52,667 --> 00:17:56,147 It helps with, uh, inotropy with a contraction, but it 292 00:17:56,147 --> 00:17:58,997 also helps in vasodilating and, you know, warming them up. 293 00:17:59,597 --> 00:18:04,217 Um, we noted that he continued to have high fever, and also his 294 00:18:04,217 --> 00:18:06,227 inflammatory markers continued to rise. 295 00:18:06,227 --> 00:18:07,817 It even reached to 500. 296 00:18:08,602 --> 00:18:11,962 And so, although with the other biochemical profile, like his blood 297 00:18:11,962 --> 00:18:17,902 gases, the electrolytes were all fine, but his clinical picture wasn't still okay, 298 00:18:18,202 --> 00:18:20,512 and something just didn't feel right. 299 00:18:21,082 --> 00:18:25,462 So at that point of time, I picked up the phone and I called my friend from the ID 300 00:18:25,462 --> 00:18:30,712 team Zaid, and I said, you know, Zaid, you know, are we missing out on something? 301 00:18:30,712 --> 00:18:33,172 Should we be investigating for anything else? 302 00:18:33,172 --> 00:18:35,542 Should I be adding another antimicrobial? 303 00:18:35,812 --> 00:18:37,222 I can't put my finger on it. 304 00:18:37,427 --> 00:18:39,827 But I feel something is not right. 305 00:18:40,367 --> 00:18:41,497 So what did you say, Zaid? 306 00:18:43,192 --> 00:18:45,922 Yes, I, I totally agreed at that point. 307 00:18:45,922 --> 00:18:50,092 I remember driving into work that morning and this child was on my mind. 308 00:18:50,092 --> 00:18:55,732 And I went first into the ICU before any morning meetings to see 309 00:18:55,732 --> 00:19:00,112 what is going on with this child, because, uh, he's quite critical. 310 00:19:00,322 --> 00:19:03,722 Uh, he's maintaining his blood pressure, but extremities are 311 00:19:03,722 --> 00:19:06,392 very cold, um, turning dusky. 312 00:19:06,812 --> 00:19:11,582 His laboratory parameters are not really improving and it's only been 24 hours. 313 00:19:11,582 --> 00:19:15,512 But as you said, something really doesn't seem quite right with 314 00:19:15,512 --> 00:19:20,642 this child, and he's very, uh, critical or very worried about him. 315 00:19:20,702 --> 00:19:25,442 Um, I was relatively new as an ID consultant and uh, I was really 316 00:19:25,442 --> 00:19:27,872 starting to panic a little bit. 317 00:19:28,422 --> 00:19:33,827 Um, and, uh, and, um, so at, at this point, you know, we talked 318 00:19:33,827 --> 00:19:39,117 about, uh, atypical causes, like mycoplasma, rickettsia, things 319 00:19:39,117 --> 00:19:42,722 like anaplasmosis and ehrlichiosis, Rocky Mountain Spotted Fever. 320 00:19:42,722 --> 00:19:47,372 These exist in the eastern coast of the United States and the northeast 321 00:19:47,372 --> 00:19:49,952 areas, maybe some other areas as well. 322 00:19:50,342 --> 00:19:54,482 Uh, but, uh, we haven't, we don't see them so much in Oman, but in my 323 00:19:54,482 --> 00:20:01,132 training back in the day, going back to, um, our mentors, Dr. Penelope 324 00:20:01,132 --> 00:20:05,432 Dennehy, uh, she taught us that, you know, you, you gotta think about these 325 00:20:05,432 --> 00:20:10,482 things in such situations, and you gotta also think about empiric doxycycline. 326 00:20:10,922 --> 00:20:16,022 Um, in, in our mind, we, I tried to look around and, call for some help. 327 00:20:16,442 --> 00:20:22,442 Um, and, uh, and there are some atypical bacteria and rickettsia-like, 328 00:20:22,532 --> 00:20:27,212 uh, organisms and, and more things that can involve the liver as well, 329 00:20:27,212 --> 00:20:32,042 and not respond to the usual empiric antibiotics like brucellosis, Q Fever 330 00:20:32,432 --> 00:20:35,192 possibilities for tularemia leishmaniasis. 331 00:20:35,777 --> 00:20:41,537 Maybe syphilis, uh, is, uh, would be quite acute, but unusual presentation for that. 332 00:20:41,537 --> 00:20:48,347 So, I decided to recommend to start empiric doxycycline and also call my good 333 00:20:48,347 --> 00:20:54,197 friend Dr. Badriya from the microbiology lab to help me because we're really 334 00:20:54,227 --> 00:20:57,707 worried about this child and we're not making the progress we'd like to make. 335 00:20:58,097 --> 00:21:00,917 So, Dr. Badriya had some good ideas as well. 336 00:21:01,712 --> 00:21:08,162 Yeah, so I actually bumped into Zaid while I was running to a meeting and, 337 00:21:08,162 --> 00:21:13,252 he expressed his concern about, uh, this child and lots of investigations 338 00:21:13,252 --> 00:21:17,392 were already done and some were already negative and some were still 339 00:21:17,392 --> 00:21:20,032 pending, but nothing positive so far. 340 00:21:20,542 --> 00:21:24,232 So Zaid was particularly concerned about atypical causes, 341 00:21:24,292 --> 00:21:26,182 uh, like he just mentioned. 342 00:21:26,662 --> 00:21:33,457 So we agreed that, uh, we need to do Brucella serology, uh, Q Fever serology, 343 00:21:33,457 --> 00:21:38,257 and because this is an acute presentation, so we thought of acute Q Fever. 344 00:21:38,977 --> 00:21:43,707 So we specifically, uh, wanted a PCR from whole Blood. 345 00:21:44,517 --> 00:21:49,977 So serology and PCR and the PCR we usually send to our reference lab 346 00:21:50,237 --> 00:21:56,177 in Oman, uh, along with, uh, Q fever PCR, they can do also Rickettsia PCR. 347 00:21:56,177 --> 00:21:59,912 So that would be two, uh, in the differential list 348 00:21:59,912 --> 00:22:01,922 of Zaid to be tested for. 349 00:22:02,672 --> 00:22:05,552 And again from the list of differentials. 350 00:22:05,612 --> 00:22:11,042 Uh, Zaid was also still concerned about some viruses, uh, like herpes simplex, 351 00:22:11,102 --> 00:22:14,002 uh, VZV, human herpes virus six. 352 00:22:14,452 --> 00:22:17,162 So PCRs for these were also requested. 353 00:22:17,820 --> 00:22:18,120 Right. 354 00:22:18,120 --> 00:22:21,060 So, um, we added the doxycycline. 355 00:22:21,240 --> 00:22:26,100 It was, um, on day two now, going to day three, uh, for potential zoonosis. 356 00:22:26,130 --> 00:22:30,990 And within 24 hours of initiation, we started seeing an improvement in terms 357 00:22:30,990 --> 00:22:33,320 of the fever pattern, the transaminases. 358 00:22:34,235 --> 00:22:38,705 Um, thereafter the CRP levels started coming down as well, and we were able to 359 00:22:38,705 --> 00:22:40,625 start weaning the supportive measures. 360 00:22:40,625 --> 00:22:45,085 So by day four, the fevers had resolved and, we were off inotropes 361 00:22:45,085 --> 00:22:50,245 and actually extubated, uh, the child, um, thereafter sending him to the ward. 362 00:22:50,655 --> 00:22:54,105 And then during this, uh, period of time, we received a call from a 363 00:22:54,105 --> 00:22:59,205 very smart microbiologist Badriya, with some updates, uh, from the lab. 364 00:22:59,505 --> 00:23:01,845 So, Badriya, would you like to describe them for us? 365 00:23:02,290 --> 00:23:06,820 Yeah, so I actually myself got a phone call as well from the Central Public 366 00:23:06,820 --> 00:23:13,150 Health Lab, telling us that Coxiella burnetti DNA was detected in that 367 00:23:13,150 --> 00:23:15,470 whole blood specimen that we sent. 368 00:23:15,530 --> 00:23:23,030 Uh, it was around, uh, hospital day two it was collected, and, uh, soon after 369 00:23:23,030 --> 00:23:25,580 that we also had the serology result. 370 00:23:26,210 --> 00:23:28,230 So we only do ELISA. 371 00:23:28,320 --> 00:23:29,790 We don't have IFA. 372 00:23:30,480 --> 00:23:33,670 So Coxiella phase two antibodies were positive. 373 00:23:34,180 --> 00:23:37,660 Uh, IGM was strongly positive and IgG was just above the cutoff. 374 00:23:38,920 --> 00:23:42,790 Uh, whereas the phase one antibodies were both negative. 375 00:23:43,017 --> 00:23:48,617 We repeated PCR after two weeks of the child's presentation, and it 376 00:23:48,617 --> 00:23:50,937 was negative, which was reassuring. 377 00:23:51,787 --> 00:23:56,167 We also repeated serology, uh, after two weeks and then again after four weeks. 378 00:23:56,717 --> 00:24:00,497 Phase two antibodies, both IGM and IgG remained positive. 379 00:24:01,227 --> 00:24:06,267 Phase one IgG transiently appeared, uh, at the two week sample, but 380 00:24:06,267 --> 00:24:09,797 then disappeared from the following one, which was again, reassuring. 381 00:24:10,547 --> 00:24:13,427 So, Zaid, uh, would you like to tell us what happened after that? 382 00:24:13,665 --> 00:24:13,845 Yeah. 383 00:24:13,845 --> 00:24:16,215 So the first thing we did is we went back. 384 00:24:16,545 --> 00:24:20,925 So the patient's now doing much better, uh, after a few days of doxycycline. 385 00:24:22,065 --> 00:24:24,825 And then we got this, uh, result about the Q fever. 386 00:24:24,825 --> 00:24:29,325 So the first we go back to the family and say, are you sure there was no animal 387 00:24:29,325 --> 00:24:34,605 exposure and they're like, well, uh, he actually spent likes to spend a lot of 388 00:24:34,605 --> 00:24:40,815 time at grandma's house and she has a bunch of goats in her yard and he helps, 389 00:24:40,815 --> 00:24:45,255 he spent a lot of time with her helping her tend to her goats, and some of them 390 00:24:45,255 --> 00:24:47,535 had given birth recently and all of that. 391 00:24:47,535 --> 00:24:48,210 And like, okay. 392 00:24:48,435 --> 00:24:53,655 So, so that's, that's the, that's the exposure where, where this came from. 393 00:24:54,095 --> 00:24:56,815 Thankfully everything was going very well at this point. 394 00:24:56,815 --> 00:24:59,995 He had been transferred from the ICU to the ward. 395 00:25:00,385 --> 00:25:04,165 The fever resolved for a few days, then started to come back. 396 00:25:05,005 --> 00:25:08,095 But alone, and he was otherwise, everything else was getting 397 00:25:08,095 --> 00:25:12,085 better, and so we kept extending the doxycycline duration. 398 00:25:12,175 --> 00:25:16,015 We did repeat blood cultures, we did the repeat Q fever, coxiella 399 00:25:16,045 --> 00:25:19,375 PCR, and nothing came back positive. 400 00:25:19,375 --> 00:25:23,705 And so after being on doxycycline for three weeks, we decided that 401 00:25:23,705 --> 00:25:27,155 maybe this, uh, fever was, uh, at this point, maybe a drug fever. 402 00:25:27,155 --> 00:25:30,965 We changed azithromycin and then the fever resolved. 403 00:25:30,965 --> 00:25:36,325 And then, after one week of azithromycin, we stopped all of the antibiotics 404 00:25:36,565 --> 00:25:38,325 and he did really well after that. 405 00:25:38,415 --> 00:25:40,785 Um, he recovered essentially fully. 406 00:25:41,215 --> 00:25:47,490 The bilirubin, the albumin, the ALT, they took about three weeks to normalize. 407 00:25:47,850 --> 00:25:52,680 The coagulation profile took about six weeks to, to normalize, and he kept 408 00:25:52,680 --> 00:25:58,320 following up in the hematology clinic and the sickle cell clinic for, uh, we 409 00:25:58,320 --> 00:26:02,010 have, uh, more than two years of follow up since then, and he's done very well. 410 00:26:02,415 --> 00:26:06,905 Um, so he didn't have any kind of chronic complications or chronic infection as far 411 00:26:06,905 --> 00:26:09,485 as we can, we can tell, uh, after that. 412 00:26:09,485 --> 00:26:14,495 So it was a happy ending to a very, uh, tense situation initially. 413 00:26:16,235 --> 00:26:18,185 Yeah, I mean, what an incredible case. 414 00:26:18,185 --> 00:26:23,095 I have not had a case of this, but the best part is hearing that he's doing well. 415 00:26:23,525 --> 00:26:26,315 So maybe we can talk about, what is Q Fever? 416 00:26:26,585 --> 00:26:29,705 I'm sure a lot of us need refreshers and we don't see it that often. 417 00:26:29,945 --> 00:26:30,995 How's it present? 418 00:26:30,995 --> 00:26:32,105 What should we look for? 419 00:26:32,435 --> 00:26:35,765 Um, Zaid, maybe you can tell us about some more info about Q Fever. 420 00:26:35,800 --> 00:26:36,280 Right. 421 00:26:36,280 --> 00:26:38,590 So Q fever, it has this funny name. 422 00:26:38,950 --> 00:26:43,030 It starts with the letter Q, and that apparently comes from query. 423 00:26:43,030 --> 00:26:47,290 So the initial cases were not very clear as far as the etiology. 424 00:26:47,995 --> 00:26:51,835 So they used to call them query fever, and then it became eventually Q Fever. 425 00:26:51,835 --> 00:26:57,755 And then later on the bacteria was discovered, which is a Coxiella burnetii. 426 00:26:57,775 --> 00:27:00,745 It's named after the people who, who discovered it. 427 00:27:01,255 --> 00:27:03,415 Uh, it's an intracellular bacteria. 428 00:27:03,505 --> 00:27:04,665 It's a zoonosis. 429 00:27:05,125 --> 00:27:10,040 The main reservoir are, uh, there, different animals can be the reservoir, 430 00:27:10,040 --> 00:27:15,320 but for as far as human infection, uh, the most significant would be farm animals. 431 00:27:15,320 --> 00:27:22,460 So, cattle, sheep, goats, they tend to get infected with this organism a lot. 432 00:27:22,460 --> 00:27:27,890 Sometimes there can be also outbreaks that can cause kind of abortion outbreaks. 433 00:27:27,890 --> 00:27:30,680 So like in a farm, there can be a lot of abortions all of 434 00:27:30,680 --> 00:27:32,660 a sudden among the animals. 435 00:27:32,660 --> 00:27:35,770 And that could be related to the Coxiella. 436 00:27:35,975 --> 00:27:41,755 So humans who are in close contact with farm animals mostly are the, uh, the 437 00:27:41,755 --> 00:27:43,855 highest risk usually to get infected. 438 00:27:44,345 --> 00:27:49,945 The distribution is quite worldwide, so in the US there are dozens, sometimes 439 00:27:50,005 --> 00:27:52,675 over a hundred cases, uh, in a year. 440 00:27:53,045 --> 00:27:57,260 Australia is another country where, uh, there's usually a lot 441 00:27:57,260 --> 00:27:59,660 of reports, uh, in the Middle East. 442 00:27:59,660 --> 00:28:05,450 We also have a lot of Q fever, uh, and there's a lot of communities and farmers 443 00:28:05,450 --> 00:28:09,560 and people who spend a lot of time with the sheep and with other farm animals. 444 00:28:10,170 --> 00:28:15,385 In Oman, our country specifically, the first case was diagnosed 445 00:28:15,385 --> 00:28:17,575 officially in the year 2000. 446 00:28:18,145 --> 00:28:21,665 So our, our healthcare system was a little bit late to develop, 447 00:28:21,665 --> 00:28:24,045 more like in the 1970s and 1980s. 448 00:28:24,065 --> 00:28:27,535 And so some of these diseases were not recognized by laboratory 449 00:28:27,535 --> 00:28:30,205 confirmation until maybe more recently. 450 00:28:30,565 --> 00:28:34,255 At that time, they did a sero prevalence study, and they found 451 00:28:34,255 --> 00:28:39,525 about 10% of adults were seropositive at that time in our country. 452 00:28:39,925 --> 00:28:41,455 So it's not that, uh, uncommon. 453 00:28:41,855 --> 00:28:45,655 The fever itself, the symptomatic infection, is seen a lot more 454 00:28:45,655 --> 00:28:47,450 in adults than in children. 455 00:28:47,450 --> 00:28:51,050 So children are only about 5% of all of the cases. 456 00:28:51,500 --> 00:28:54,890 Uh, so it tends to be maybe more asymptomatic and self-limited 457 00:28:54,890 --> 00:28:56,960 when occurring in children. 458 00:28:57,470 --> 00:29:04,040 The symptoms usually are a non-specific flu-like illness with fevers and 459 00:29:04,040 --> 00:29:05,840 maybe headaches and body aches. 460 00:29:06,410 --> 00:29:09,680 It can be sometimes presenting as fever of unknown origin. 461 00:29:10,190 --> 00:29:13,620 Uh, it has a tropism for the lungs and for the liver. 462 00:29:13,620 --> 00:29:16,410 So you can see atypical pneumonia. 463 00:29:16,680 --> 00:29:18,000 You can see hepatitis. 464 00:29:18,280 --> 00:29:22,220 Sometimes less commonly, it can be associated with encephalitis 465 00:29:22,220 --> 00:29:24,590 or, or, uh, pericarditis. 466 00:29:25,400 --> 00:29:29,630 Um, in children, the prognosis is usually good, but there are reports 467 00:29:29,630 --> 00:29:32,270 of severe cases, including deaths. 468 00:29:32,640 --> 00:29:37,260 One of the severe manifestations is acute fulminant hepatitis, and, and that's 469 00:29:37,260 --> 00:29:39,870 been described in children and in adults. 470 00:29:40,320 --> 00:29:45,450 There is also in about 1 - 5% patients, there's progression to chronic 471 00:29:45,450 --> 00:29:50,265 infection, and that usually manifests with osteomyelitis, which can be 472 00:29:50,265 --> 00:29:53,985 multifocal and also endocarditis. 473 00:29:53,985 --> 00:29:58,455 And endocarditis usually here happens in the setting of patients who 474 00:29:58,455 --> 00:30:04,275 already have underlying, uh, heart disease like valvular heart disease. 475 00:30:04,572 --> 00:30:04,812 Right. 476 00:30:04,812 --> 00:30:08,942 So, uh, Badriya, As Zaid was just mentioning that, it's through reservoirs 477 00:30:08,942 --> 00:30:13,472 or farm animals, but what is the actual mode of transmission, uh, for Q Fever? 478 00:30:14,807 --> 00:30:20,132 So, transmission to humans occurs mainly through the inhalation of 479 00:30:21,297 --> 00:30:25,497 contaminated aerosols from infected animals or infected environments. 480 00:30:25,947 --> 00:30:30,162 Um, Coxiella is able to survive in the environment for a very long time. 481 00:30:30,892 --> 00:30:37,462 So, even non-direct exposure to animals can still cause, uh, Q Fever and 482 00:30:37,462 --> 00:30:43,102 as Zaid mentioned, birth byproducts like placenta and amniotic fluid. 483 00:30:43,162 --> 00:30:47,917 These particularly have very high numbers of bacteria. 484 00:30:48,577 --> 00:30:53,547 And so exposure to these is a very high risk like this child had. 485 00:30:53,547 --> 00:30:56,627 So he was basically, there at the wrong time. 486 00:30:56,627 --> 00:31:00,757 So he was there in an environment where goats gave birth recently. 487 00:31:01,567 --> 00:31:05,737 Uh, and so I think that's probably the way he got it unfortunately. 488 00:31:06,487 --> 00:31:11,107 There are some other less common modes of transmission, but these are less common. 489 00:31:11,107 --> 00:31:14,667 And some of them are actually rare and some are not even proven. 490 00:31:15,357 --> 00:31:19,017 And these include, uh, percutaneous exposure like for example, 491 00:31:19,017 --> 00:31:21,892 through cuts in the skin while dealing with animal products. 492 00:31:22,922 --> 00:31:27,212 It could also be through ingestion of, for example, unpasteurized milk. 493 00:31:28,262 --> 00:31:32,912 Uh, and possibly it could be tick bone, possibly. 494 00:31:33,632 --> 00:31:37,652 And there has been some rare instances of person to person transmission, 495 00:31:37,652 --> 00:31:41,402 like for example, vertical transmission, sexual, uh, through 496 00:31:41,402 --> 00:31:43,772 transfusion and through transplants. 497 00:31:43,974 --> 00:31:47,089 Yeah, and you know, we talked a little bit about the testing that was sent 498 00:31:47,089 --> 00:31:51,589 for this patient, but maybe Badriya, if you could summarize again for 499 00:31:51,589 --> 00:31:56,089 us, how do we think about screening and confirming this diagnosis, 500 00:31:56,089 --> 00:31:57,559 particularly since it's so uncommon. 501 00:31:57,604 --> 00:31:58,114 Right. 502 00:31:58,114 --> 00:32:01,654 So, so to start with, uh, you know, a disclaimer, uh, 503 00:32:01,654 --> 00:32:03,064 I'm not an expert in Q Fever. 504 00:32:04,114 --> 00:32:07,504 Maybe we should have invited somebody from Australia to go through this. 505 00:32:07,554 --> 00:32:14,574 The CDC has actually published, uh, a very useful document in 2013, and I 506 00:32:14,574 --> 00:32:16,704 always go back, uh, to that document. 507 00:32:16,754 --> 00:32:20,174 It's basically describes the diagnosis and the management of Q Fever. 508 00:32:20,989 --> 00:32:26,799 And it also provides criteria for labeling a case as confirmed or as probable. 509 00:32:27,769 --> 00:32:33,449 So in general, when it comes to testing for Q Fever, testing basically aims 510 00:32:33,449 --> 00:32:38,879 to either detect the organism itself, and that would be mostly by PCR. 511 00:32:39,599 --> 00:32:42,119 But there are some other methods like, for example, culture. 512 00:32:43,029 --> 00:32:48,219 Uh, which is generally not recommended as it is difficult and it has, 513 00:32:48,249 --> 00:32:53,259 you know, exposure risk, and, uh, there's also immunohistochemistry. 514 00:32:54,219 --> 00:32:56,829 Uh, so this allows us to detect the organism. 515 00:32:56,889 --> 00:33:00,549 The other way is to detect the antibodies against the organism, 516 00:33:00,579 --> 00:33:02,679 so that would be using serology. 517 00:33:03,549 --> 00:33:08,529 And the best method would be by indirect immunofluorescence assay, because that 518 00:33:08,529 --> 00:33:12,699 actually provides titers and titers are very important in the diagnosis 519 00:33:12,699 --> 00:33:19,039 of Q Fever because, for example, a confirmed acute case of Q Fever requires 520 00:33:19,579 --> 00:33:24,869 either the detection of Coxiella in a clinical sample, or, the demonstration 521 00:33:24,869 --> 00:33:30,599 of a fourfold rise in phase two IgG titers between paired serum that are 522 00:33:30,599 --> 00:33:33,239 collected three to six weeks apart. 523 00:33:34,209 --> 00:33:39,804 For, uh, chronic Q Fever, again, laboratory confirmation requires either 524 00:33:39,804 --> 00:33:44,484 the detection of the organism in a clinical sample or the demonstration 525 00:33:44,484 --> 00:33:50,094 of antibodies, but this time against phase one antigens that goes with 526 00:33:50,094 --> 00:33:56,464 chronic Q fever and the titers that are diagnostic are more than or equal to 800. 527 00:33:57,184 --> 00:34:01,204 Uh, or if using doubling dilution, it'll be, uh, 1024. 528 00:34:02,394 --> 00:34:07,334 So, in our lab, as I have mentioned earlier, we use ELISA, 529 00:34:07,724 --> 00:34:09,704 which does not provide titers. 530 00:34:10,034 --> 00:34:14,674 However, fortunately because we managed to catch the organism on time and we 531 00:34:14,674 --> 00:34:19,944 managed to get a positive PCR result, this was a confirmed case by definition. 532 00:34:20,187 --> 00:34:20,547 Yeah. 533 00:34:21,447 --> 00:34:25,557 And you know, thinking about the other features about this case that are a bit 534 00:34:25,557 --> 00:34:30,917 unique is, um, this patient's history of sickle cell disease and I thought maybe 535 00:34:30,917 --> 00:34:36,137 I'd ask about this concept of acute sickle hepatopathy and and what that means. 536 00:34:37,087 --> 00:34:37,417 Right. 537 00:34:37,417 --> 00:34:42,337 So the, this case was very fascinating because of the presence of the 538 00:34:42,337 --> 00:34:46,007 sickle cell disease, the severe liver involvement, and then the Q fever. 539 00:34:46,027 --> 00:34:50,317 So we really looked at the literature to see what is there about sickle 540 00:34:50,317 --> 00:34:53,147 cell disease and Q fever, and actually we couldn't find any case 541 00:34:53,747 --> 00:34:59,032 of Q fever reported in the setting of sickle cell disease itself. 542 00:34:59,032 --> 00:35:03,372 So it's very fascinating in case this one, showing like the 543 00:35:03,372 --> 00:35:06,282 intersection of these two diseases. 544 00:35:06,672 --> 00:35:11,362 Uh, so, but acute sickle hepatopathies, this is an entity that's quite 545 00:35:11,362 --> 00:35:15,337 known in patients with sickle cell disease, some studies estimate 546 00:35:15,337 --> 00:35:21,187 that up to 10% of patients with vaso-occlusive crisis can have, uh, 547 00:35:21,277 --> 00:35:23,677 hepatopathy or liver involvement. 548 00:35:24,167 --> 00:35:25,667 It actually, they're quite dangerous. 549 00:35:25,667 --> 00:35:29,117 So there can be, the mortality in some studies can be 11 to 550 00:35:29,117 --> 00:35:33,947 14% in, in adults, uh, probably lower in children, thankfully. 551 00:35:34,837 --> 00:35:38,107 There are different types of acute sickle hepatopathy. 552 00:35:38,107 --> 00:35:44,247 So, the first one is, uh, thought to be the, uh, hepatic crisis, uh, 553 00:35:44,277 --> 00:35:48,017 which is basically vaso-occlusive crisis involving the liver. 554 00:35:49,162 --> 00:35:52,822 There, there would be some tender hepatomegaly, elevated liver 555 00:35:52,822 --> 00:35:55,042 enzymes, fever, and mild jaundice. 556 00:35:55,042 --> 00:35:58,072 But it's not very severe presentation. 557 00:35:58,432 --> 00:36:04,042 Uh, but the next is what we started to see in our patient is hepatic sequestration. 558 00:36:04,462 --> 00:36:08,842 And here there's sequestration within the sinusoids of the, of 559 00:36:08,842 --> 00:36:13,932 the liver and, and, and there you get very massive hepatomegaly. 560 00:36:14,262 --> 00:36:19,422 It's very tender and you get severe anemia and you start to see direct 561 00:36:19,422 --> 00:36:24,072 hyperbilirubinemia, but the liver transminases are not yet severely 562 00:36:24,462 --> 00:36:28,542 elevated and maybe the most severe form, probably progressing from there 563 00:36:28,872 --> 00:36:34,847 is intra hepatic cholestasis, where then you have all of the previous findings 564 00:36:34,847 --> 00:36:39,997 plus the, uh, marked elevation of the transaminases and progressive liver 565 00:36:40,297 --> 00:36:44,587 failure, which is what we started to, which we we're seeing in in our patients. 566 00:36:45,862 --> 00:36:51,052 And so, so what we think happened here is that the, the Coxiella having 567 00:36:51,052 --> 00:36:56,932 the hepatic tropism probably caused this liver inflammation, and that 568 00:36:56,962 --> 00:37:02,067 triggered maybe the more sickling of the red blood cells in the sinusoids 569 00:37:02,752 --> 00:37:07,267 leading to hepatic sequestration, which then leads to maybe sinusoidal 570 00:37:07,597 --> 00:37:13,117 dilatation, compression of the biliary tree, and intrahepatic cholestasis. 571 00:37:13,487 --> 00:37:16,727 That's, you know, our hypothesis of the, of the process. 572 00:37:17,127 --> 00:37:20,667 These acute sickle hepatopathies are well described with a lot of 573 00:37:20,667 --> 00:37:24,057 other infectious agents, especially those that affect the liver, like 574 00:37:24,057 --> 00:37:29,097 hepatitis viruses and Epstein-Barr virus and even autoimmune disease. 575 00:37:29,517 --> 00:37:30,687 Uh, they can happen. 576 00:37:30,687 --> 00:37:34,647 But with Q Fever, this seems to be for us as, as far as we could 577 00:37:34,647 --> 00:37:36,687 tell, this was the first report. 578 00:37:36,687 --> 00:37:39,817 We also looked at maybe other Rickettsia. 579 00:37:40,027 --> 00:37:42,367 Well, Q fever is not exactly a rickettsia disease. 580 00:37:42,367 --> 00:37:45,727 It's a category of its own, but it's related, uh, they're kind of 581 00:37:45,727 --> 00:37:49,192 like cousins with rickettsia and legionella, if you could say, um. 582 00:37:50,072 --> 00:37:55,832 So we, we did find there was some cases of uh, anaplasmosis, uh, 583 00:37:55,832 --> 00:37:58,682 there's one case of anaplasmosis and hemoglobin SC that was quite 584 00:37:58,682 --> 00:38:01,502 severe, presented multi-organ failure. 585 00:38:01,922 --> 00:38:07,892 Uh, but besides that, I suppose there could be some similar presentations with 586 00:38:07,922 --> 00:38:12,597 ricketssial disease or maybe anaplasmosis or, or any hepatotropic basically, 587 00:38:12,597 --> 00:38:17,587 uh, bacteria or infectious agent could present with acute sickle hepatopathy. 588 00:38:17,897 --> 00:38:22,697 So that was a very, uh, unique and fascinating aspect to, to this case. 589 00:38:22,697 --> 00:38:27,017 And, uh, and we could be at, at least happy that the child had 590 00:38:27,017 --> 00:38:29,987 a very good recovery, although we were really worried about him 591 00:38:29,992 --> 00:38:31,547 at, at, at the time he presented. 592 00:38:31,692 --> 00:38:31,932 Yeah. 593 00:38:33,072 --> 00:38:37,422 Well, I always like to wrap up by opening it up just to ask if 594 00:38:37,422 --> 00:38:41,442 you have any additional comments or lessons that you've learned. 595 00:38:41,442 --> 00:38:46,002 You've been really great at pointing out things that stood out to you as we went, 596 00:38:46,002 --> 00:38:47,742 but anything else you'd like to add? 597 00:38:48,432 --> 00:38:52,512 Well, I mean, I would say is that, you know, whenever the clinical course 598 00:38:52,512 --> 00:38:56,442 doesn't go as expected, sometimes you get this gut feeling, even if 599 00:38:56,442 --> 00:38:57,527 you can't put your finger on it. 600 00:38:58,182 --> 00:39:01,692 You know, think again, go back to the beginning, you know, what did we miss? 601 00:39:01,842 --> 00:39:05,412 And don't hesitate to call up a friend and ask for help. 602 00:39:05,652 --> 00:39:08,442 You know, different specialties, just putting their heads together and 603 00:39:08,442 --> 00:39:09,607 trying to come up with a solution. 604 00:39:09,973 --> 00:39:17,803 From my side, I have to say that I really admired, um, Zaid's perseverance and 605 00:39:17,803 --> 00:39:22,543 he went back and actually asked again about the exposure history, even though 606 00:39:22,543 --> 00:39:25,213 he got a no, no, no, the first time. 607 00:39:25,843 --> 00:39:29,593 Uh, but you know, he went again and he asked again. 608 00:39:29,593 --> 00:39:32,773 So, uh, I really admired that and. 609 00:39:33,288 --> 00:39:38,308 Another thing I would add is sometimes you really have to seize 610 00:39:38,308 --> 00:39:43,048 the moment, like they say, and catch the organisms at the right time. 611 00:39:43,048 --> 00:39:47,743 So I'm really glad that we got that first sample for Coxiella PCR, because 612 00:39:48,433 --> 00:39:54,073 it soon disappears after that, and it did actually disappear after two weeks. 613 00:39:54,133 --> 00:39:59,363 And since we don't have IFA, our ELISA wouldn't have been diagnostic. 614 00:39:59,423 --> 00:40:01,873 Uh, but we caught it at the right time. 615 00:40:01,933 --> 00:40:03,103 So I'm glad we did that. 616 00:40:03,343 --> 00:40:05,833 From my, uh, point, uh, of view. 617 00:40:06,043 --> 00:40:08,143 So one, one thing that was interesting about this case, 618 00:40:08,143 --> 00:40:10,603 why did we send the Q fever PCR? 619 00:40:10,603 --> 00:40:15,373 And I was like, um, running around the hospital, worried about this patient, 620 00:40:15,403 --> 00:40:19,158 and, different people would offer their ideas as to what's going on. 621 00:40:19,353 --> 00:40:22,138 And one of the residents, he stood in front of me and said, 622 00:40:22,168 --> 00:40:23,608 have you thought about Q Fever? 623 00:40:24,343 --> 00:40:26,398 And I'm like, why? 624 00:40:26,758 --> 00:40:28,678 Why are you thinking about Q Fever? 625 00:40:32,338 --> 00:40:35,818 And apparently he had seen some cases in, in adults, like in 626 00:40:36,238 --> 00:40:37,918 adult in medicine rotations. 627 00:40:38,548 --> 00:40:41,608 Uh, and, and that got me like reading about it. 628 00:40:42,508 --> 00:40:46,278 I asked Badriya about it and she's like, yeah, we can send a PCR, I, 629 00:40:46,408 --> 00:40:49,048 because I, I never seen a case before. 630 00:40:49,048 --> 00:40:53,068 It's not very common in children and we just read about it in textbooks. 631 00:40:53,068 --> 00:40:57,748 Like it, uh, it's very rare to see the actual symptomatic case in a child, 632 00:40:57,748 --> 00:41:03,053 and so, uh, thankfully I had the humility to listen to the resident and 633 00:41:03,053 --> 00:41:07,313 go with that and, you know, so I think that's very important to, to listen 634 00:41:07,313 --> 00:41:12,773 to people even as we progress in our career, to always listen to everyone 635 00:41:12,803 --> 00:41:15,083 and take their ideas very seriously. 636 00:41:15,513 --> 00:41:20,993 And I think that another important point here, empiric doxycycline sometimes when 637 00:41:20,993 --> 00:41:25,513 things are looking unusual atypical. 638 00:41:25,513 --> 00:41:27,988 Um, I think it saved this child's life. 639 00:41:28,498 --> 00:41:32,218 Uh, and in fact, if anything, I would say maybe we start a little 640 00:41:32,218 --> 00:41:33,478 bit late on the second day. 641 00:41:33,568 --> 00:41:36,948 Maybe we could have even started earlier with the empiric doxycycline. 642 00:41:37,058 --> 00:41:40,718 So, uh, that's I think another important lesson here. 643 00:41:41,308 --> 00:41:47,158 Uh, so yeah and thank god for microbiologists, right? 644 00:41:48,675 --> 00:41:51,045 Thanks so much to our guests today for joining Febrile. 645 00:41:51,405 --> 00:41:54,735 Don't forget to check out the website febrilepodcast.com where 646 00:41:54,735 --> 00:41:57,225 we post the Consult Notes, which are written supplements of the 647 00:41:57,225 --> 00:42:01,245 episodes with links to references, our library of ID infographics, 648 00:42:01,305 --> 00:42:02,685 and a link to our merch store. 649 00:42:03,555 --> 00:42:07,365 Febrile is produced with support from the Infectious Diseases Society of America. 650 00:42:08,205 --> 00:42:11,175 Please reach out if you have any suggestions for future shows or 651 00:42:11,175 --> 00:42:12,675 wanna be more involved with Febrile. 652 00:42:13,035 --> 00:42:13,845 Thanks for listening. 653 00:42:14,025 --> 00:42:15,595 Stay safe and I'll see you next time.