Episode 105
105: On Flea-k
Drs. Maria Gabriela Segura, Misti Ellsworth, and Michael Chang from UTHealth Houston McGovern Medical School and Children’s Memorial Hermann Hospital chat about an unusual pediatric case of fever of unknown origin.
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Febrile is produced with support from the Infectious Diseases Society of America (IDSA)
Transcript
Hi everyone, welcome to Febrile, a cultured podcast about all things infectious disease.
Sara Dong:We use consult questions to dive into ID clinical reasoning, diagnostics, and antimicrobial management.
Sara Dong:I'm Sara Dong, your host and a MedPeds ID doc.
Sara Dong:Today, we are joined by a team from the University of Texas Health Science Center or UTHealth in Houston, McGovern Medical School and Children's Memorial Hermann Hospital.
Sara Dong:First up, I'll introduce our host, Dr.
Sara Dong:Maria Gabriela Segura.
Sara Dong:She is a third year pediatric infectious diseases fellow at UTHealth Houston.
Gaby Segura:Hi, I go by Gaby and I'm very grateful for being here today and excited to record this episode with you.
Sara Dong:She is joined by two discussants.
Sara Dong:Dr.
Sara Dong:Misti Ellsworth is an Associate Professor of Pediatrics and Director of Pediatric Infection Prevention.
Misti Ellsworth:Hi, I'm Misti Ellsworth, and I'm excited to be here today on the Febrile podcast.
Sara Dong:We also have Dr.
Sara Dong:Michael Chang, an Assistant Professor of Pediatrics and Co Director of the Pediatric Antimicrobial Stewardship Program.
Michael Chang:Hi, I'm Michael Chang, and I'm also very excited to be here today.
Sara Dong:So, before we jump into the case, we always ask our one question as everyone's favorite cultured podcast.
Sara Dong:I like to ask the guests to share a little piece of culture, really just something non medical that makes you happy or that you enjoy doing.
Sara Dong:So, Gaby, maybe I'll start with you.
Gaby Segura:Yes.
Gaby Segura:Yeah, we were talking about this a lot, really, like, outside of work, for me, I like to run.
Gaby Segura:I do like to watch a lot of Netflix and HBO shows.
Gaby Segura:The main thing is spending time with my kids.
Gaby Segura:I have two boys, a seven year old and a two year old.
Gaby Segura:We like to travel, mostly to beach destinations, and pretty much doing anything with my husband and my kids is my outside thing
Sara Dong:Love it.
Sara Dong:Love it.
Sara Dong:What about you, Misty?
Misti Ellsworth:So, I was super excited this week that The Bear Season 3 came out on Hulu, so pumped about that.
Misti Ellsworth:And then I've been reading Agatha Christie novels because it's too hot to go outside.
Sara Dong:Yeah, I have the new season of The Bear queued up, but hopefully I'll start some of them this weekend.
Sara Dong:I'm excited.
Sara Dong:And you, Michael, what do you have?
Michael Chang:Yeah, so right before we started recording, we were talking about how I've been listening to so much K pop because my daughter's like a huge K pop fan, but my culture moment isn't actually about K pop.
Michael Chang:So I, there's a band from London called The Last Dinner Party.
Michael Chang:And I think that was like the first album I had listened to that wasn't K pop in like months.
Michael Chang:It was such a breath of fresh air.
Michael Chang:And I was like, Oh my God, I didn't even know I needed this.
Michael Chang:And so I probably listened to that album twice a week, all the way through like every week since like January.
Michael Chang:It's so good.
Michael Chang:Yeah.
Michael Chang:They're like a, kind of a rock theatrical group.
Michael Chang:All women.
Michael Chang:It's awesome.
Michael Chang:So, uh, highly recommend if you've never heard of The Last Dinner Party, check them out.
Sara Dong:I love it.
Sara Dong:Um, well, I am going to hand it over to Gaby who's going to lead us through today.
Sara Dong:It sounds like you had a case of fever of unknown origin.
Gaby Segura:Yes.
Gaby Segura:So, a usual month in service, I get a call from the pediatric team about a previously healthy 11 year old girl, she was admitted for the workup of fever of unknown origin.
Gaby Segura:In the middle of winter in the Texas Gulf Coast region, she started having fevers and decreased energy.
Gaby Segura:Mom says like she wouldn't get out of bed.
Gaby Segura:She was doing Tylenol as needed.
Gaby Segura:It improved the symptoms for a little bit and then she would again feel very tired and having non quantified temperatures, uh, fever.
Gaby Segura:On the second day, mom took her to an urgent care.
Gaby Segura:They did, they swapped her for strep throat, COVID, and flu.
Gaby Segura:Everything was negative.
Gaby Segura:So that same afternoon at home, she had a temperature that they quantified to 101 F.
Gaby Segura:They stayed at home with Tylenol as needed, but on the fourth day of illness, she's still not improving, so she went to PCP.
Gaby Segura:PCP diagnosed her with left otitis media and prescribed amoxicillin, which she was taking but didn't really improve at any point with it.
Gaby Segura:So on day five, mom again came to the ED, they did a UA, they did a rapid mono test, they got another group A strep test, COVID, and a chest x ray.
Gaby Segura:All of them were normal.
Gaby Segura:While she was on the ED, her temperature went up to 102.
Gaby Segura:7 F.
Gaby Segura:By now, about a week after the symptoms started, she's still having daily fevers, very tired, and now having a new onset non productive cough.
Gaby Segura:However, they explained that the cough would persist until she vomits, and so the mom, again, took her to the ED for assessment once this started.
Gaby Segura:So in the ED, her temperature was 102.7 F she was noted to be tachycardic and just looking ill, so she ended up being admitted for FUO workup.
Gaby Segura:They stopped the amoxicillin that she was still on because at this point they didn't see any physical exam findings that were consistent with acute otitis media.
Gaby Segura:They got a blood culture and a urine culture, and then she was brought up to the floor.
Gaby Segura:So for her past history, her birth history was unremarkable, no pertinent past medical history, no surgeries, and family history was also unremarkable.
Gaby Segura:Her immunizations were up to date.
Gaby Segura:She lives with mom, dad, and her sister, they don't have any pets, and she's not around any animals that she's aware.
Gaby Segura:Mom stays at home, dad works in carpet installations, they both go to school, both sisters.
Gaby Segura:There were no sick contacts or no other exposures in the history.
Gaby Segura:So, when we saw her the first time, her vital signs were unremarkable.
Gaby Segura:She was afebrile at that point and on room air.
Gaby Segura:And her, the rest of her physical exam, the only significant finding was rash that we thought it was consistent with keratosis pilaris on both upper arms.
Gaby Segura:And mom had said that it, she's had that in the past.
Gaby Segura:So we weren't sure if this was really like a worsening of the same rash or if it was just her baseline keratosis pilaris.
Gaby Segura:And then she didn't have any edema in upper extremities or no skin peeling.
Gaby Segura:Nothing in throat, ears, no lymph nodes were present at that time.
Gaby Segura:So, the initial labs that they collected, she, uh, had a mild anemia with a hemoglobin of 11.9, mild thrombocytopenia of 156.
Gaby Segura:Her inflammatory markers were a little high with a ESR of 23 mm/hr, a CRP of 36 mg/L, and procalcitonin of 0.4 ng/mL.
Gaby Segura:And her CMP had a mildly elevated AST to 111.
Gaby Segura:The primary team did a further workup of ANA, COVID IgG, group A strep PCR, a transplant respiratory viral panel, CMV antibodies, EBV panel, HIV and mycoplasma PCR, all of those were negative.
Gaby Segura:This is the case that we have.
Gaby Segura:So based on this presentation, Dr.
Gaby Segura:Ellsworth, what are you, what would be your differentials so far?
Misti Ellsworth:Okay, so to summarize, we have a 13 year old girl with fever for one week with fatigue, mild rash, cough and emesis with lab results showing a mild anemia, mild thrombocytopenia, some elevated inflammatory markers and LFTs.
Misti Ellsworth:And she's also been taking oral amoxicillin with really no improvement in her symptoms.
Misti Ellsworth:Overall, I'd say our symptoms are non specific, and, you know, it could really be caused by multiple different infections.
Misti Ellsworth:Uh, seasonality can often help when we're considering the differential diagnosis in these cases, and this was the winter in the Gulf Coast of the United States.
Misti Ellsworth:So since it's winter, of course, we're gonna think about all those viral etiologies, such as flu, RSV, parainfluenza, adeno[virus], all those things should be considered with her nonproductive cough.
Misti Ellsworth:Other viruses with similar symptoms include SARS CoV 2, and then of course there's other viral causes with nonspecific syndromes that we always think about like enterovirus and Epstein Barr virus.
Misti Ellsworth:For bacterial infections, you know, I would consider community acquired pneumonia or a group A streptococcal infection, but she's received oral amoxicillin without benefit, so makes those things maybe less likely.
Misti Ellsworth:Despite the cough with primarily nonspecific systemic symptoms, she could have a developing septic arthritis or osteomyelitis secondary to Staph aureus or Kingella.
Misti Ellsworth:However, Kingella is less likely given her age.
Misti Ellsworth:So urinary tract infections and urosepsis should be considered, but her testing was reported to be negative.
Misti Ellsworth:Uncommon, but meningococcal infections, and with the appropriate epidemiologic factors like travel, consider typhoid, leptospirosis, but both these would be rare.
Misti Ellsworth:At 11 years of age, it's also worthwhile to obtain a sexual history, consider infections such as disseminated gonococcal infection or syphilis.
Misti Ellsworth:Acute HIV could present with nonspecific symptoms as well.
Misti Ellsworth:Um, in our region, we also should always consider some vector borne illnesses.
Misti Ellsworth:So murine typhus is often missed because it has very nonspecific presentation, can have an uncomplicated clinical course, and the fact that only a small portion of patients recall a flea bite or exposure to infested animals.
Misti Ellsworth:Other nonspecific manifestations can include myalgias, malaise, nausea, vomiting, and abdominal pain with tenderness in more than half of the cases.
Misti Ellsworth:Bartonella henselae infection or cat scratch disease is also pretty high yield for your FUO diagnosis, with proper travel history, we might also consider ehrlichiosis or Rocky Mountain Spotted Fever.
Misti Ellsworth:So sometimes in our region, we do see things that are considered tropical illnesses, so we should put that on our differential too.
Misti Ellsworth:So things like Zika, dengue, and possibly malaria if we find the right risk factors or history.
Misti Ellsworth:There are numerous pediatric inflammatory conditions like Kawasaki disease, staphylococcal and streptococcal toxic shock syndrome, and macrophage activation syndromes that could also present with her symptoms.
Misti Ellsworth:Gaby, I think additional imaging and echocardiogram can help us.
Misti Ellsworth:Also, is there any additional history that might be helpful?
Gaby Segura:Yes.
Gaby Segura:So, for imaging, we have a chest x ray that was normal.
Gaby Segura:We had an echo done on the 11th day of illness.
Gaby Segura:This was read as normal too.
Gaby Segura:And then we got an abdominal ultrasound, of course, part of FUO workup as well, that showed non occlusive thrombus within the mid aorta.
Gaby Segura:There was some, uh, trace left pleural effusion, hepatomegaly with left kidney above the second standard deviation for her age.
Gaby Segura:So when we got this result, we got a aortic ultrasound that, again, showed previously seen hyperechoic filling defect in the upper abdominal aorta, seen again, causing non occlusive thrombosis.
Gaby Segura:They don't really specify the measures of the clot, they just said the proximal aortic diameter was 1.4cm and the mid aortic diameter is 1.0cm.
Gaby Segura:So with this result, we got a second echo once we found these aortic thrombus, and the repeat echo showed mild dilation of the proximal left main coronary artery with a normal sized mid portion of the left main coronary artery.
Gaby Segura:So, hematology was consulted and they recommended a workup that included protein C, protein S, anthrombin activities, lupus anticoagulant, beta 2 glycoprotein, cardiolipin, and factor 5 Leiden.
Gaby Segura:All of those were normal.
Gaby Segura:So what do you think we should have in consideration with this information as a differential diagnosis?
Misti Ellsworth:So, the normal chest radiograph doesn't exclude but does make community acquired pneumonia less likely, especially with the later onset of her cough.
Misti Ellsworth:A viral or respiratory tract infection also seems less likely.
Misti Ellsworth:With the ultrasonography and echocardiography findings, inflammatory syndromes such as Kawasaki's disease, multisystem inflammatory syndrome in children, or MIS C, or macrophage activation syndrome are higher on the differential.
Misti Ellsworth:Some of the systemic viral infections remain a possibility, such as EBV virus, um, and adenovirus.
Misti Ellsworth:I think Febrile episode number 96 in April was about Kawasaki's disease, so I think that is less likely.
Misti Ellsworth:Bacterial infections related to vasculitis like murine typhus, Rocky Mountain spotted fever should still be considered, especially with the right epidemiological history.
Misti Ellsworth:An unusually severe case of cat scratch may still be on the list as well.
Misti Ellsworth:At this point, with the echocardiogram findings, it'll be difficult to exclude Kawasaki's disease, and we would consider asking our cardiology and rheumatology colleagues for help while we continue our infectious disease evaluation for murine typhus, and cat scratch disease.So, Gaby, what did we find?
Gaby Segura:So, back to our patient, we found a typhus IgG antibody of 1:64 and then typhus IgM antibody of 1:128.
Gaby Segura:Before this result was obtained, since the presentation of the patient was concerning for FUO, a Karius testing was sent and it resulted positive for typhus as well.
Gaby Segura:So, finally after two weeks after her symptoms started, our patient was started on doxycycline.
Gaby Segura:She did also receive IVIG because of this coronary dilation that we found, uh, per rheumatology and concerns about atypical Kawasaki disease.
Gaby Segura:The serologies were, of course, obtained before the IVIG was given.
Gaby Segura:So at this point, she also had an MRI of her chest, abdomen, and pelvis, which showed interval resolution of the previously visualized feeling defect within the abdominal aorta that was seen in the aortic ultrasound.
Gaby Segura:They still reported a trace left pleural effusion and a trace pericardial effusion as well, and free fluid in the pelvis.
Gaby Segura:Then a two week echo repeat was normal, and the mid left main coronary artery size, which was improved compared to the prior study taken a week before.
Gaby Segura:So we saw her in clinic about a month after she was discharged and the typhus IgM result at that visit came back at 1:256.
Gaby Segura:While our patient did receive treatment for Kawasaki disease, we felt that this patient had a very unusual, severe case of murine typhus, especially with the serologies and even the Karius being positive.
Gaby Segura:So Dr.
Gaby Segura:Ellsworth, in your experience, how common is murine typhus and how is it transmitted?
Misti Ellsworth:Murine typhus, also known as endemic typhus or flea borne typhus, is caused by Rickettsia typhi.
Misti Ellsworth:The primary way that it spreads among rats and then to humans is through flea bites, although other flea species can also carry it.
Misti Ellsworth:Fleas become lifelong carriers after biting infected rats, which are the natural host for Rickettsia typhi.
Misti Ellsworth:Interestingly, possums and feral cats have become significant sources of murine typhus in the United States, especially in suburban areas where cat fleas play a role.
Misti Ellsworth:The same flea also spreads Rickettsia felis, which causes a syndrome that looks just like Rickettsia typhi.
Misti Ellsworth:Transmission happens through the flea feces, which contaminates wounds or enters through the broken skin from flea bites, and there's even a possibility of inhalation of the fecal material.
Misti Ellsworth:Murine typhus is found worldwide, particularly in warm climates with lots of rats, cats, or possums and their associated flea populations.
Misti Ellsworth:While cases can occur year round, in the U.
Misti Ellsworth:S., most are reported from April to October in places like Southern California, Southern Texas, the Southeastern Gulf Coast, and Hawaii.
Misti Ellsworth:Interestingly, it tends to affect adult males more often.
Misti Ellsworth:In children, though, both boys and girls get it equally, although they might not realize they've been bitten by fleas, which often leads to underdiagnosis.
Misti Ellsworth:Back in the 1940s, the U.
Misti Ellsworth:S.
Misti Ellsworth:saw a big drop in reported cases thanks to using DDT to control fleas.
Misti Ellsworth:However, since murine typhus was removed from the list of diseases that doctors must report nationally in 1987, the true number of cases today is uncertain.
Misti Ellsworth:Texas, where it's still a reportable disease, saw a notable increase from 157 cases in 2008 to over 500 a year from 2017 to 2019, peaking at 730 cases in 2018.
Misti Ellsworth:But even with those numbers, studies suggest there are likely more cases that aren't being diagnosed, especially in places where the disease is common.
Misti Ellsworth:A study done by Purcell and colleagues in South Texas looked at antibodies for typhus in 513 kids aged one to 17, and found about 13 percent of them had antibodies.
Misti Ellsworth:This tells us that there could be a lot more cases out there than what's being reported.
Misti Ellsworth:It's likely that we're missing quite a few because of how tricky the disease can be to spot.
Gaby Segura:So in your, again, what you typically see is murine typhus, a common explanation for FUO.
Gaby Segura:And what does the typical murine typhus case look like?
Gaby Segura:Do you think this case is unusual?
Gaby Segura:How does murine typhus cause symptoms
Misti Ellsworth:Rickettsia typhi is a gram-negative, obligate intracellular bacteria that infects systemic vascular endothelial cells resulting in inflammatory, lymphohistiocytic vasculitis, and vascular injury that may affect any organ.
Misti Ellsworth:And this is what leads to the typical clinical and laboratory findings that we see in our patients.
Misti Ellsworth:As we stated earlier, murine typhus is often missed due to its nonspecific presentation, typically its uncomplicated clinical course.
Misti Ellsworth:Again, most people do not recall flea bites or flea infestations, like in our patient who could not recall any exposures.
Misti Ellsworth:Symptoms start within 3 days to 2 weeks after contact with the infected flea, and typical symptoms include fever, headache, body aches, and muscle pain.
Misti Ellsworth:A maculopapular rash appears around the end of the first week of illness and occurs in around 50 percent of patients.
Misti Ellsworth:The rash is usually on the patient's trunk, although extremities can be involved, including the palms and soles.
Misti Ellsworth:About 10 percent of patients may even present with petechiae.
Misti Ellsworth:It's important to note that the lack of rash should not exclude the diagnosis of murine typhus.
Misti Ellsworth:The classic triad of fever, headache, and rash only occurs in one third to one half of patients.
Misti Ellsworth:Common laboratory abnormalities include elevated liver enzymes, elevated LDH, thrombocytopenia, and a high sedimentation rate (ESR).
Misti Ellsworth:Murine typhus is typically self limited and resolves in one to two weeks.
Misti Ellsworth:In our region, anecdotally, I would say that murine typhus and cat scratch disease are high yield tests for us when evaluating patients with fever of unknown origin.
Misti Ellsworth:This was certainly an unusually severe case, though complications of murine typhus have been reported in up to 30 percent of cases, with severe disease occurring more often in adults.
Misti Ellsworth:The most common complications include pulmonary issues such as pneumonia, pulmonary effusion, respiratory failure, followed by central nervous system involvement, such as altered level of consciousness, meningitis, seizures, ataxia, and acute kidney injury.
Misti Ellsworth:Less frequently reported complications include DIC, septic shock, or multi organ failure, and hemophagocytic syndrome.
Misti Ellsworth:Severe hemolysis has been reported in patients with glucose 6 phosphate dehydrogenase deficiency, hemoglobinopathies, and thalassemia.
Misti Ellsworth:Overall, about 5-10% of cases require ICU admission, and overall case fatality rate is estimated to be 0.
Misti Ellsworth:4%.
Misti Ellsworth:Data from Whiteford et al.
Misti Ellsworth:suggest that a substantial portion of pediatric patients had severe illness characterized by a febrile interval of 14 days or more, that was 23 percent of patients, or hospitalization of 7 days or more, that was 36 percent of patients.
Misti Ellsworth:Once the appropriate therapy has been initiated, which we'll talk about in a bit, most patients defervesce rapidly within 1-3 days.
Gaby Segura:Given the broad differential diagnosis, it seems like there could be a diagnostic confusion.
Gaby Segura:Michael, as our diagnostic and antimicrobial steward expert, you actually published an article about MIS C versus typhus, right?
Michael Chang:Right.
Michael Chang:Common symptoms of typhus are primarily symptoms of systemic inflammation and systemic vasculitis.
Michael Chang:And so the common symptoms that Dr.
Michael Chang:Ellsworth just discussed, that's a really broad differential diagnosis, uh, like we went over, overlapping with many infectious syndromes as well as non infectious syndromes like Kawasaki disease or MIS C.
Michael Chang:And so, just to quickly review, the most common method for the diagnosis of murine typhus are paired acute and convalescent serologies, which our patient had and confirmed a diagnosis of acute murine typhus.
Michael Chang:But immunohistochemical staining and PCR in tissue can be performed by select labs.
Michael Chang:And in this case, Karius testing was positive, but very little data is actually available on the performance of that test for the diagnosis of murine typhus.
Michael Chang:So with all that said, we had a really interesting experience at the start of the SARS CoV 2 pandemic, where we suddenly had several previously healthy patients presenting with signs of systemic inflammation with elevated C reactive protein, triglycerides, procalcitonin, ferritin, as well as liver inflammation.
Michael Chang:And they all had fever and rash.
Michael Chang:And this was just a few weeks after the first publications about MIS C or PIMS TS were coming out of Europe.
Michael Chang:And so the Pediatric ID Service was actually consulted to see these patients for concerns of MIS C.
Michael Chang:Our fellow at the time, Dr.
Michael Chang:Zain Al Amarat, who's now a PEDS ID faculty at UAMS in Arkansas, uh, was concerned though, because in our region at the time, the incidence of SARS CoV 2 was still quite low that we knew of.
Michael Chang:And so we had started testing everyone at the time and none of these patients tested positive or had known exposures to patients or people with positive SARS CoV 2 tests.
Michael Chang:And so Dr.
Michael Chang:Alamarat obtained a thorough history and discovered that all the patients had dog exposures, several with known fleas.
Michael Chang:Again, being the excellent clinician that she is, she also noted that the WBC counts, the white blood cell counts, and platelets were on the low side or the low end of normal.
Michael Chang:And so what she suspected was happening was that we were actually having an increased incidence of murine typhus, which we were able to confirm with serologic testing.
Michael Chang:And so she was able to summarize all these findings and this experience in an article published in the Pediatric Infectious Diseases Journal.
Michael Chang:And what's even more interesting is that our friends, Dr.
Michael Chang:Andrea Dean down the street from us at Texas Children's Hospital also reported the same experience at the same time and also published in another journal.
Michael Chang:To this day, neither our friends down the street at Texas Children's or here at Memorial Hermann, we're still not sure why this happened and why we had a spike.
Michael Chang:We, you know, speculate that maybe it's because kids were out of school because of school closures, or more people were outside with their pets because, you know, being outside was a lower risk of transmission , or maybe because of the media attention, paid to MISC, maybe more parents were seeking medical attention.
Gaby Segura:Dr.
Gaby Segura:Chang, what is considered as first line treatment for typhus?
Michael Chang:So to date, there are actually no clinical trials conducted regarding the treatment of murine typhus.
Michael Chang:Recommendations are based on the analysis of retrospective studies.
Michael Chang:So doxycycline is the treatment of choice regardless of patient age, and early diagnosis is usually based on clinical suspicion and epidemiology.
Michael Chang:Treatment should not be withheld awaiting confirmatory laboratory results in order to avoid severe and potentially fatal complications.
Michael Chang:So, there is this, like, deeply rooted aversion to prescribing doxycycline for pregnant women and pediatric patients less than 8 years old.
Michael Chang:You'll recall, maybe, that tetracyclines were discovered in the 1940s and have broad spectrum activity against many types of bacterial pathogens.
Michael Chang:And they're actually the drug of choice for tick and flea based infections like murine typhus, Rocky Mountain spotted fever, and ehrlichiosis.
Michael Chang:So, why is there this aversion to doxycycline in children and pregnant women?
Michael Chang:Well, tetracycline, we know, binds to calcium, which can stain permanent teeth in children and potentially inhibit bone growth to a degree.
Michael Chang:In mouse models, it did lead to skeletal problems in mouse embryos when given 11 times the human dose.
Michael Chang:But we also know that tetracyclines can cross the placenta.
Michael Chang:And so, because of this historical information, tetracyclines were not used in pregnant women.
Michael Chang:women nor for children under the age of eight years until all their permanent teeth were in.
Michael Chang:But, I think it's important to remember that doxycycline is not tetracycline.
Michael Chang:Doxycycline was actually a second generation drug synthesized in 1972.
Michael Chang:It has decreased calcium binding, but unfortunately there's really no clinical data in pregnancy for doxycycline.
Michael Chang:And so the FDA currently says that there have been no published human data showing that fetal exposure to doxycycline causes cosmetic staining of the primary teeth.
Michael Chang:However, this cannot be ruled out because of the tetracycline class effect, quote.
Michael Chang:Which is to say that because doxycycline is in the tetracycline class, we don't know for sure because we don't have any data.
Michael Chang:They also say that there's no data to prove that doxycycline is safe, but also cite a review of the teratogen information system at the University of Washington School of Public Health, which is considered a global reference for teratogenic safety, which suggests that normal doses of doxycycline during pregnancy are unlikely to pose a
Michael Chang:risk, so lacking evidence for harm, it's important to note that doxycycline is recommended as the first line drug in pregnancy for post exposure prophylaxis for anthrax.
Michael Chang:So for kids, there is at least one published study from 2007 from Volovitz, uh, et al.
Michael Chang:titled, The Absence of Two Staining with Doxycycline Treatment in Young Children, in which the authors tried to make the title as clear as possible related to their findings.
Michael Chang:But interestingly, even seven years after the publication of that article, clinicians were still hesitant to give doxycycline to patients less than eight years of age.
Michael Chang:And this was described in another paper, uh, Zientek et al, uh, and that paper was called The Self-Reported Treatment Practices by Healthcare Providers Could Lead To Death from Rocky Mountain Spotted Fever.
Michael Chang:And this survey worryingly showed that for kids under the age of eight years of age, providers were not prescribing doxycycline, which is the drug of choice, when concerned about Rocky Mountain spotted fever, despite the fact that pediatric patients less than nine years of age have the highest case fatality rate of any age group for Rocky Mountain spotted fever.
Michael Chang:And so one of the leading factors to mortality in Rocky Mountain spotted fever is delay in diagnosis and delay in initiation of appropriate therapy with doxycycline.
Michael Chang:So this actually got the attention of the CDC and this concerned them so much that the next year, the CDC, in a paper in 2015, Todd et al.
Michael Chang:published a paper called No Visible Dental Staining in Children Treated with Doxycycline for Suspected Rocky Mountain Spotted Fever.
Michael Chang:And so I think they were just trying to be very, very clear that you should be giving doxycycline when you're worried about tick or flea borne illnesses as empiric therapy.
Michael Chang:And so, the takeaway of all of this is please do not hesitate to prescribe doxycycline in children if you suspect a vector borne illness like murine typhus or Rocky Mountain spotted fever.
Gaby Segura:So just to summarize and confirm, it is okay to use doxycycline in children?
Michael Chang:Yes, absolutely.
Michael Chang:And just to emphasize again, you should definitely not withhold treatment while awaiting laboratory confirmation of murine typhus or other vector borne illnesses.
Michael Chang:And so once you do start the doxycycline, though, fever resolves quickly, usually one to three days after starting therapy, and with clinical improvement, treatment should be continuing for at least three days after the patient becomes afebrile, and the total treatment course is usually seven to fourteen days.
Gaby Segura:So, what can we do to decrease the transmission of typhus, particularly in endemic zones like us?
Michael Chang:From what is known, we do think that prior infection provides lasting immunity, but there's no vaccine for murine typhus.
Michael Chang:So the key here really is avoidance and elimination of flea vectors and rodent infested areas.
Michael Chang:And as we mentioned previously, the U.
Michael Chang:S.
Michael Chang:was successful in reducing the incidence of murine typhus with the pesticide DDT to control flea vectors, but obviously, with the unintended consequences of DDT.
Michael Chang:So that said, you still have to control the fleas before hosts, as fleas can easily find other hosts, as in Texas, where it seems that in addition to rodents, the possums and feral cats that Dr.
Michael Chang:Ellsworth mentioned are playing a role in transmission.
Michael Chang:Always, though, flea control is easier said than done, but if you have pets, you definitely want to make sure you clean areas where fleas can breed, like pet bedding, rugs.
Michael Chang:You want to treat your pets per your vet[eranarian]'s instructions and, potentially calling a pest control expert if you're having a lot of problems.
Michael Chang:Uh, and this may take several cycles and potentially months to achieve.
Michael Chang:You can also minimize possum and rodent exposure by making sure your waste bins are secured, make sure your sandboxes are covered to avoid feral cats using them as litter boxes, and yeah.
Michael Chang:And so I think typhus is a super cool infection because it really shows the complex interactions between human behavior, societal structures, and nature that allow infections to propagate.
Sara Dong:What a great finale.
Sara Dong:And thank you guys so much for sharing this.
Sara Dong:I've never had a case of murine typhus, so I definitely learned a lot.
Sara Dong:And to help us wrap up, maybe Gaby, could you summarize with a few take home points?
Gaby Segura:Yes, sure, so I would say first to just keep in mind that a few patients with murine typhus can actually recall having a flea exposure or infestation with fleas.
Gaby Segura:So obviously getting a good history is important, but even if you don't get that exposure and the symptoms are consistent, just have that diagnosis in the back of your mind.
Gaby Segura:Then I would, I would also say that remember, very few patients have all the classic symptoms.
Gaby Segura:So symptoms can be very non specific.
Gaby Segura:And then as soon as you, as you're thinking about the diagnosis, just go ahead and start doxycycline, regardless of the age, and just don't hesitate if you're suspecting this.
Gaby Segura:And, don't wait for labs to be resulted before starting.
Sara Dong:A big thanks to Gaby, Misti, and Michael for joining Febrile.
Sara Dong:Don't forget to check out the website febrilepodcast.
Sara Dong:com where you'll find the Consult Notes which are written in complements to the episodes with links to references, our library of ID infographics, and a link to our merch store.
Sara Dong:Febrile is produced with support from the Infectious Diseases Society of America or IDSA.
Sara Dong:Please reach out if you have any suggestions for future shows or want to be more involved with Febrile.
Sara Dong:Thanks for listening, stay safe, and I'll see you next time.
