Infectious Disease Puscast #91

From Microbe TV, this is Infectious Disease Puscast, episode 91, recorded Hello everyone. I'm Dr. Daniel Griffin and unfortunately this is solo, no Dr. Sarah Dowing today, but she will be back in two weeks. Uh she's busy with her uh clinical and teaching responsibilities. So uh I guess this teaching responsibility didn't fit in this time, but uh she she will be back. So uh

Without the banter, we will just move forward. Um, welcome to another podcast. References, as always, are available in our uh show notes. Um at microbe.tv, the home of our growing multimedia empire. Uh Puscast is a review of the infectious disease literature for the last two weeks that we found interesting or entertaining. And now on to the literature, shall we?

I'm gonna start off with our uh our viral section and reminding all our listeners to listen to uh TWIV this weekend virology, both the uh clinical update and the deep dive. Uh sometimes things kind of at both areas, but uh sort of try to have um each of them stay a little bit in their own lane. So if you listen to both you get more of a full picture of what's been going on.

Um, but let us start off with the first article, the article comparison of two doses versus one dose in the first season, children are vaccinated against influenza. uh systematic review and meta-analysis published in JAMA Network Open. I feel like this one I may have actually also discussed on the uh clinical update because it was just that good.

And and and some of the things I mentioned on the clinical update, we always keep talking about influenza. And one of the things I like to try to remind everyone is that influenza really causes considerable pediatric morbidity and mortality. Um an estimated 20% of children, so one in five children each year are infected. Children younger than five have the highest hospitalization rates for influenza of any age.

Did you get that? Under five highest hospitalization rates for flu of any age group. Um last year almost three hundred children got sick enough that they died from the flu. So the WHO recommends that flu vaccine naive children aged under nine receive two doses of influenza vaccine at least four weeks apart with one dose each year thereafter.

A A P the American Academy of Pediatric recommends that children aged six months through eight years receive two doses of flu vaccine in the same season if it's their first time. Um so think about it as the first time your child has not gotten the flu shot before, you get one, four weeks later, boom, you get the second, and then after that it'll be a yearly.

Um that's great and all, right? That's American Academy of Pediatrics, that's CDC, that's WHO. Um, but here these researchers ask the very important research question, which is does research evidence support? a two-dose schedule in the first year of vaccination for influenza vaccine naive children younger than nine years.

They performed a meta analysis that included fifty one studies four hundred and fifteen thousand fifty participants to estimate the increase in vacu vaccine effectiveness of a second inactivated influenza vaccine dose. The pooled absolute increase in vaccine effectiveness of a second inactivated influenza vaccine dose in the first year of vaccination was 15 percentage point. Um

For those younger than nine and twenty-eight percentage points for those younger than three. So really making a a big difference um you know in the sort of the highest risk group. Um some really nice figures. There's a nice uh figure three uh where we get forest plus. uh is another figure two, I'm kinda doing these backwards um uh where you you look again getting forest plots. So really really nice um really compelling data saying that those recommendations do make.

All right, and so for more virology related stuff, be sure to listen to Pluto.

All right, moving right into bacterial. Will say on this infectious disease podcast. A lot of interesting um articles. So bacterial, be sure to listen to this week in microbiology. A lot. great stuff I was just listening to to today about how the microbiome um is associated with increased risk of pancreatic cancer, um, how the the oral microbiome actually influences uh Sleep and frailty, fascinating stuff.

Um, well here we have a couple articles. And the first article is performance of different versions of Duke criteria in diagnosing infective endocarditis in patients with intracardiac prosthetic materials published in Open Form Infectious Disease. So the authors start off the article with the sentence, diagnosing infective endocarditis.

is a significant challenge. And I I like that opening sentence, um, as I think it can be often overlooked um in retrospect or once the time has gone by and all the information um is is then available. Um, you know, when we see the large vegetation have persistently positive blood cultures despite twenty-four hours of appropriate antibiotics, it seems so straightforward.

Um to perhaps demonstrate how the challenge here is that this study brings up that the Duke criteria is not the only criteria employed in making the The study aimed to compare the diagnostic performance of the twenty fifteen sixty. and 2023 European Society of Cardiology and the 2023 International Society for Cardiovascular Infectious Diseases, ISCBID Duke Clinical Criteria.

in a cohort of patients with suspected um infectious endocarditis and intracardiac prosthetic material. So so for background. Yes, I think, you know, I guess I guess I've sorta came into this game in the middle. I w I was not a practicing physician in nineteen eighty one. Um, but the first Duke criteria were published in nineteen ninety four.

Um and these replaced the nineteen eighty one Rhine Beth Israel criteria, right? So quite a quite a gap there, right? Say thirteen years. We'll talk about why. Um, so then we get the 1994, the first two criteria, and then we get a number of validation studies, and then In two thousand, we get the updated modified Duke criteria, so published in two thousand. And then we have this

gap until the most recent, at least when it comes to Duke criteria, a gap until the most recent Duke criteria updated twenty twenty three, right? So for twenty three years. We've been using the same modified Duke criteria, but here we get the most recent. Duke criteria updated 2023. And and we discussed that updated 2023 Duke criteria on the infectious disease Puscast 28. And I'll leave a link in there. Sarah was discussing that.

So here we have the results of a retrospective study conducted at two Swiss university hospitals. The reference standard was the diagnosis of the endocarditis team or expert clinicians. Patients with infectious endocarditis, the reference standard, classified as definite infective endocarditis by the DU criteria are considered true positives, while those without Um infectious endocarditis classified as rejected, i.e., or considered true negatives.

So just sort of what what's going on here and why are there all these gaps between. Um so you come out with criteria. the expert panel puts these out there. And then you end up with studies like this where they look through and they basically test the criteria. D do they work? Do they do they actually validate when we look at them? So Of the 1025 episodes with suspected I.E., infective endocarditis. I'm just gonna say endocarditis, but no, I guess I'll say infective.

Um so of the 1,025 episodes with suspected IE and intracardiac prosthetic materials, um 61% had IE. Um using the 2015 ESC, 2023 ESC, and the 2023 ISCVID, that's the updated Duke clinical criteria, 32%. thirty six percent and forty two percent episodes were classified as definite, i.e. respectively. Um they they calculate sensitivity for the 2015 Duke, the 2023 Duke.

The 2023 Duke, and so that's a 2015 Duke ESC, the 2023 Duke ESC, and the 2023 Duke ISCBID. The clinical criteria were calculated to be 56%. sixty one percent and seventy one percent. Uh With sixty seven. fifty six. and 34% respectively. So really interesting here, right? That in this context, in this validation, the specificity of the 2023 most recent due criteria is only 34%.

So equally worrisome, you might say, was that the sensitivity for these different criteria ranged from 56 to 71%. So you're really missing some when it comes to sensitivity. But also you're overdiagnosing with a specificity of only thirty five. So they conclude that the 2023 ISCVID Duke Clinical Criteria demonstrated the highest sensitivity for diagnosing.

um infectious endocarditis in the presence of intracardiac prosthetic material compared to the the twenty fifteen and the twenty twenty three um ESC, right? So European Society of Cardiology. Um however this increased sensitivity came at the expense of specificity, um which was lower with the twenty twenty three ISCBID.

Most recent Duke criteria. Notably, the improved sensitivity and reduced specificity were largely attributable to the inclusion of newly classified typical microorganisms in the presence of prosthetic intracardia.

All right. So with that context, um, i is it okay to to wait a little to make sure we have the diagnosis? Should everyone just be throwing on antibiotics um when they hit the door just because it's in the differential? Well In open form infectious disease, we have the article with a title that catches the eye. Infective endocarditis and antimicrobial timing, a a case for delay. Question mark.

Um in patients with suspected infective endocarditis, current guidelines recommend prompt initiation of empiric antimicrobial treatment. After obtaining blood cultures. However, the clinical benefit of immediate treatment in hemodynamically stable patients remains uncertain. So this study assessed the impact of deferring antimicrobial treatment in patients with suspected I.E.

Here, the investigators conducted a multi-center cohort study of adult patients with bacteremia and a clinical suspicion of i.e. infective endocarditis from two university hospitals. Patients presenting with sepsis, ICU admission, neutropenia, or clearly identifiable focus other than IEU are excluded. All cases were ad ad adjudicated by a dedicated endocarditis team as either I.E. or not I.

30-day mortality for confirmed I.E. cases. The composite outcome included 30-day mortality, new embolic events, or new bone and joint. Among 1,230 episodes, empirical antimicrobial treatment was initiated immediately. That's our group one. um after blood culture collection in six hundred and seventy-five episodes and deferred until preliminary blood culture results, group D, maybe that's group I and group D. I couldn't figure that out in 555 episodes.

Um thirty day mortality was not different between groups I and D. Five percent versus five percent. Um of five hundred and ninety-seven confirmed IE episodes. Um forty nine percent. Um infective endocarditis. 55% were in group one, 45% in group D, group I, group D. The composite primary endpoint thirty-day mortality, new embolic events or new bone and joint infection, occurred in twenty-eight percent of the group where antimicrobial therapy was initiated immediately.

versus twenty four percent in the group where they deferred start of antibiotics until preliminary bone blood culture results were available. Um, I'm gonna point out because I don't like people, the the trend issue. Despite this trend toward better outcomes in patients where antibiotics were deferred. This did not reach statistical significance. We've got a p value here of 0.304. So Um really nice graphical abstract for infective endocarditis and antimicrobial timing, a case for delay.

uh maybe a case of saying um you know there's there's no harm with delay. Um we despite the trend, I'll say no statistical significance, um, and really nice here as they have in this in this graphical abstract. Five percent thirty day mortality starting right away. Five percent thirty day mortality um waiting for those preliminary results.

All right. And MMWR. Oh my gosh. Um You know, people who've following the news may be aware that there's a little bit of a issue going on or not. We're not sure the everyone at the M M W R at the C D C was fired or not, depending upon the hour. So They got a message you were fired, and some people got a message you weren't really fired, April Fools. Who knows? But you know, just my heart goes out to the the people at the CDC. And another example of the great work with the MMWR.

Tularemia, antimicrobial treatment and prophylaxis. CDC recommendations for naturally acquired infections and bioterrorism response. United States twenty twenty five seems to have caught people's attention as I get emails and see YouTube comments. So Uh here we have again a nice graphical abstract, but for background, we read that tularamia is a rare but potential serious disease caused by Francisella tularensis. an a highly infectious non motile gram negative coco bacillus.

Um F. tularensis is endemic throughout the northern hemisphere, with the majority of annual infections reported from the United States, Turkey, and Northern Europe. Approximately two hundred to three hundred cases of tularemia, also known as rabbit fever or deer fly fever, are reported in the United States annually. Cases have been reported from every state except Hawaii. I suspect there's an issue with underdiagnosis, but let us continue.

Humans can be exposed to F. tularensis through various routes, including bites from arthropods, ticks, deer flies, and mosquitoes. Uh cutaneous exposure through butchering and other contact with infected animals, ingestion or contaminated food and water, contact with contaminated soil or hay, and inhalation of aerosolized particles. on the boards you're always s skinning a rabbit and cutting yourself or or you know

Uh or maybe getting you know, finding ticks from that that rabbit you're skinning all over you. Who knows, by the way? Um in 2012, F. Tularensis was classified by the US Federal Select Agent Program as a Tier One Select Agent, indicating the greatest risk for use during a bioterrorism attack. based on its history of weaponization, stability in the environment, and an infectio infectious dose as low as ten organisms. Ouch.

Um now the US and the Soviet Union included the bacterium in their biological weapons stockpiles during the 50s and 60s. Uh these countries as well as Japan and the UK are known to have researched the bioweapon potential. um of F. Tularensis. They've got a nice reference that you can go to there. Now one documented US study during nineteen sixty-six to nineteen sixty-seven, Operation Red Cloud, involved mechanical dissemination.

of Francisella tulorensis into an Alaskan forest to investigate distribution and decay rates. Um I'm gonna leave a link into here to the article tularemia a storied history an ongoing thread. If you wanna read more about this uh stuff. They have a nice section in this article that goes through some updated changes. That article also has lots of great tables. So keep this one bookmarked, you know, for when when you see one of those cases.

Um I I expect up to date and other resource to incorporate um these recommendations. So Um, you know, they go through treatment recommendations for adults and children. Um, you know, when treatment initiation is delayed, Cypro Leviquin or Genomycin is preferred over doxy, treatment duration ten days, um, you know, really some nice

uh recommendations, treatments for pregnant women, post-exposure prophylaxis. So great, great stuff there. But you know the the drugs we're thinking about here are are doxy and the the fluoroquinolones in in general.

All right, moving on to fungal. Um, we have the article risk factors associated with progression to clinical. Candida, orus infection among adults with previous colonation. Florida twenty nineteen twenty twenty three. So here they identified 105 case patients with documented clinical specimens after colonization and five hundred and seventy-eight control subjects with colonization only. Factors significantly associated with clinical cases included presence of five or more COVID.

Conditions. Uh, that's gonna give you a tenfold increase. Uh, four or more invasive devices, odds ratio two point nine two. And three or more recent medical procedures, odds ratio 2.32. Also fully dependent care required for eating, odds ratio 2.8, mobility, 2.15, and trans.

1.82 are associated with clinical case progression. So really nice seeing here that uh you know when you're comparing folks that are colonized with C. auris and folks that are actually infected, um, there tend to be a number of uh different.

All right, and now we're gonna move on to uh parasitic. Uh And uh be sure to listen to this week in parasitism. We just this last Friday recorded um the the the answer to our uh our recent mystery case, and I'll say our emailers did quite well there. Um

So be sure to listen to this week in parasitism. But uh I I was just actually talking about this today, you know, I was thinking of heading back to Africa this December, but it looks like I could just stay here in the US and see cases of locally acquired malaria. The article public health response to the first locally acquired malaria.

outbreaks in the US in 20 years was published in JAMA Network Open. And they start by asking the question, why were there four outbreaks of domestic malaria in 2023 after 20 years with no locally acquired cases? Now, in 2023, the U.S. reported ten locally acquired mosquito-transmitted malaria cases of four genetic lineages in four states.

Um the first such outbreaks detected in twenty years and the largest in thirty five years Uh the qualitative study was um an interdisciplinary public health response to the locally acquired malaria outbreaks in May. To december twenty twenty three. I included case investigations, enhanced case finding, um, PCR analysis of captured anophiles uh mosquitoes for uh plasmodium uh parasites, novel targeted amplicon sequencing of plasmodium in patient

Public health interventions included incident command activation, clinical outreach, community awareness, vector control. Patient data were acquired through public health surveillance as part of national notifiable disease surveillance. So this study included um ten patients. Um uh mean age thirty nine point five.

Um seventy percent were male from Florida, Texas, Maryland, and Arkansas with locally acquired mosquito transmitted malaria, and seven hundred and eighty-three anophiles mosquitoes across four states. No patient had a recent history of international travel or bloodborne exposures. outbreak cases had an epidemiological link within, but not across state lines.

Uh P. Vivax was detected in three Anophiles crucians in Florida. Sequencing data showed that all Florida P Vivax cases shared the same plasmodium strain. The Texas and Arkansas P vibec cases were genetically distinct from each other and from Florida's cases. All nine P vibax strains had genetic signatures that were consistent with Central and South American origin. Maryland's P falciparum parasites were consistent with African origin.

Um the outbreaks as as I think we're aware of were contained. So some great figures, but I just want to walk through these a little with with us. Maybe David will have these up on the screen for the YouTube watchers. So Figure one number of imported malaria cases by species in the US and this is nineteen seventy two to twenty twenty two. We see that we see our COVID dip right in twenty twenty and then right back up there.

Um, but you can really see total cases rising over time. You can actually see the Vivax cases um actually trending down um and really seeing more um falciparum cases. Um figure two is great because you could really look at, you know, number of malaria cases by US states. Um and you could see there really are places where where this clusters, right? And as as we discussed, uh these these folks uh somehow the um

uh the mosquitoes are are getting it. Uh they're in our country and so we're seeing it there. But but here this is just total number of malaria cases by state, right? Most of these, right, are people coming from as we see here, south of the border or from uh sub Saharan Africa, um, but also we have had cases. know where folks come from, Asia. Um, but you can see w which which are the hot states that greater than fifty eight, uh California, Texas, Florida, Georgia.

Virginia, Maryland, um, New York, uh, New Jersey. Interesting enough, we also see um Massachusetts, Ohio, Minnesota. Um and then figure three I really like. This is a timeline of locally acquired malaria outbreaks by species in US states. Uh they go from nineteen eighty up to twenty twenty three. And they actually have a couple of these outbreaks. The the the little outbreak in California in eighty six with twenty-eight cases, another California in nineteen eighty eight with thirty.

cases and then you see just a little bit going along and then, you know, we see boom these these recent um you know, outbreaks in in twenty twenty three with uh the one in Maryland, uh the one in Texas, the one in Florida.

All right, and wrapping us up, this is going to be a shorter one this week, the article in miscellaneous. Fever in sepsis revisited. Is a little heat what we need? Uh this was published in Open Forum Infectious Disease. Um and I have to say this should be required reading. You know, whenever fever comes up on round, I I wax eloquently about what is a normal fever and all the variation that goes in. Um but maybe more importantly is uh we're so quick to treat fever. Uh what should we be doing?

Here they discussed studies with, are you ready for this? Improved antibiotic MICs with higher temperatures. It was really nice graphic where you could see if you're, you know, if you're above 41, truly hyperthermic. Or if you're below 37C, truly hypothermic, you really kind of want to get into this range. But actually, as you're as you're seeing, if you're at these higher temperatures, you're gonna get better antibiotic MICs.

They also remind us, and this is something we've covered recently, that antipyretics can actually increase microbial mutation frequency. Um they mentioned some studies of uh septic ICU patients, no clear mortality benefit, potential harms with interesting enough, external cooling, um sort of arguing here for, oh my gosh, acimetophenophen or Tylenol. Um I know why everyone calls it Tylenol. It's hard to say paracetamol or

Cetaminophen. At the end of the day, I have to say, we need more science here. Are we actually helping our patients by treating those fevers? Or are we thwarting an ancient adaptive response in mammals to infectious challenges?

All right, well that brings us to the end of this puscast. As always, the references for this show are available at microbe.tv, the home of our growing multimedia empire. You can find the infectious disease puscast at Apple Podcasts, microbe.tv forward slash puscast.

or grab it with your favorite podcatcher or on YouTube where you can subscribe, like us, ring the bell, leave those wonderful comments. I have to say that comments are much nicer for infectious disease puscasts than happens for some of those other shows. Uh we'd love to get your questions, comments, and paper suggestions. Send them to puscast at microbe.tv. If you like what we do or you just want us to keep doing it, consider supporting the science shows of microbe TV.

at microbe.tv forward slash contribute or parasites without borders and click on the donate button. Um Sarah Dong will be back in two weeks. In the meantime, you can find her on blue sky at Sarah Windong dot febropodcast.com or at Febrile podcast dot com. I'm Daniel Griffin and you can find me at Columbia University Irving Medical Center or at Parasites Without Borders dot com, as well as on the other podcasts this week in Parasitism and this week in Virology Clinical.

And as always, thank you for this most interesting consultation and allowing us to participate in the care of this most difficult and challenging case. We shall continue to follow along with you. Thank you, and dictation, and goodbye. Thanks for listening. We'll be back in two weeks. Another podcast is in