The Unvaccinated Child with Fever

This episode of PEM Currents: The Pediatric Emergency Medicine Podcast focuses on the approach to unvaccinated or undervaccinated children aged 3–36 months presenting to the ED with fever. Host Brad Sobolewski reviews differences in immune response, risk for serious and invasive bacterial infections, and outlines evaluation strategies including labs, imaging, and empiric antibiotics. He highlights data showing increased interventions in this population and calls for local guideline development. The episode emphasizes thoughtful, individualized care in the context of rising vaccine hesitancy and declining immunization rates.

Learning Objectives

• Compare the clinical presentation of bacterial infections in unvaccinated and undervaccinated children versus fully immunized children in the Emergency Department
• Assess the need for empiric antibiotics and diagnostic testing in an unvaccinated or undervaccinated child presenting with fever without source

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References

Curtis M, Kanis J, Wagers B, et al. Immunization status and the management of febrile children in the pediatric emergency department: what are we doing? Pediatr Emerg Care. 2023;39(1):1-5. doi:10.1097/PEC.0000000000002864

Finkel L, Ospina-Jimenez C, Byers M, Eilbert W. Fever without source in unvaccinated children aged 3 to 24 months: what workup is recommended? Pediatr Emerg Care. 2021;37(12):e882-e885. doi:10.1097/PEC.0000000000002249

Herz AM, Greenhow TL, Alcantara J, et al. Changing epidemiology of outpatient bacteremia in 3- to 36-month-old children after the introduction of the heptavalent-conjugated pneumococcal vaccine. Pediatr Infect Dis J. 2006;25(4):293-300. doi:10.1097/01.inf.0000207485.39112.bf

Kaufman J, Fitzpatrick P, Tosif S, et al. Faster clean catch urine collection (Quick-Wee method) from infants: randomised controlled trial. BMJ. 2017;357:j1341. doi:10.1136/bmj.j1341

Kuppermann N, Fleisher GR, Jaffe DM. Predictors of occult pneumococcal bacteremia in young febrile children. Ann Emerg Med. 1998;31(6):679-687. doi:10.1016/S0196-0644(98)70225-2

Rutman MS, Bachur R, Harper MB. Radiographic pneumonia in young, highly febrile children with leukocytosis before and after universal conjugate pneumococcal vaccination. Pediatr Emerg Care. 2009;25(1):1-7. doi:10.1097/PEC.0b013e318191dab2

Trippella G, Galli L, De Martino M, Lisi C, Chiappini E. Procalcitonin performance in detecting serious and invasive bacterial infections in children with fever without apparent source: a systematic review and meta-analysis. Expert Rev Anti Infect Ther. 2017;15(11):1041-1057. doi:10.1080/14787210.2017.1400907

Van den Bruel A, Thompson MJ, Haj-Hassan T, et al. Diagnostic value of laboratory tests in identifying serious infections in febrile children: systematic review. BMJ. 2011;342:d3082. doi:10.1136/bmj.d3082

Transcript

Note: This transcript was partially completed with the use of the Descript AI

 Welcome to PEM Currents: The Pediatric Emergency Medicine P odcast. As always, I’m your host, Brad Sobolewski, and this episode is gonna focus on a challenging yet. Unfortunately, timely clinical question, what do we do with the UN or under vaccinated child who presents to the emergency department with fever? So what are we gonna go over in this episode?

Well, we’re gonna compare the clinical presentation of bacterial infections in unvaccinated and unvaccinated children versus fully immunized children in the emergency department, and we will assess the need for empiric antibiotics and diagnostic testing in this challenging population. Now, before you listen to this episode, I will presume that you are all familiar with the recommended child and adolescent immunization schedule for children ages 18 and younger in the United States or wherever you live.

So I’ll pause for a moment so that you can review that. Great. Welcome back, and there’s a few definitions that I will use. Unvaccinated or unm. Immunized means that you have no vaccines. Unvaccinated or under immunized means that you have some but not all of your vaccines, and you should always verify vaccine status via history EMR records and state registries.

So I think the first important question to answer is, when is a child immunocompetent? And honestly, competency is sort of on a sliding scale, and a child is immunocompetent if they have a normally functioning immune system capable of mounting an effective response to infections. So this means you have intact, innate and adaptive immunity with functioning neutrophils, macrophages, T cells, and B cells.

You don’t have. Severe combined immunodeficiency like a primary immunodeficiency or a secondary immunodeficiency. You’re on chemo or you’re severely malnourished. Immunocompetent kids respond to vaccines completely immunized, so greater than two doses of PCV and HIB should be immunocompetent against those bugs.

Unvaccinated or under vaccinated children are functionally immunocompromised in specific clinical scenarios such as fever without source. And it can be hard to figure out what immuno competency by disease and vaccine status really means. And so I do encourage you to be familiar with some of the information provided by the CDC as long as it’s still online.

So how common is it for children to be unvaccinated in the United States? Unfortunately. It’s getting more common. So as of the 2023-24 school year, about 3.3% of US kindergartners had an exemption from one or more required vaccines. That data is up versus 2022. 2023 translates to about 80,000 kids in the United States, and vaccination coverage varies across states.

So in the 2023-24 school year. MMR coverage was 79.6% in Idaho, and 98.3% in wild, wonderful West Virginia. 14 states reported exemption rates greater than 5% and in generally 95% vaccination rate for diseases needed for herd immunity. And we often wonder is the question of, well, is your kid’s vaccines up to date?

A good enough question, and let’s be honest, many of us just rely on adult caregivers to give us this information. Is your kid up to date on shots? Yeah, sure. I’ve had a few where up to date meant we were up to date in our decision to stop vaccinating them three years ago. EMR confirmation and state records are better and all 50 states, district of Columbia and some US territories do have immunization information systems.

And I’d encourage you to be familiar with and sign up for accounts on all of the different states that you work in. So for me, that’s Ohio, Kentucky, and Indiana. How often do we see UN or under vaccinated kids in the ed? And unsurprisingly, this number is not known. I asked some ID experts and we haven’t broadly assessed our rate, and we could do this, but it would take really a manual query of state vaccine records for any patient that doesn’t have vaccine status in the EMR.

And it would be timely and laborious though. Interesting. In Indiana, Curtis et al did a retrospective review of almost 800 well-appearing febrile children three to 36 months throughout 2019, presenting in one Indiana pediatric emergency department, and they were really looking at vaccine status. They excluded children with complex chronic illnesses like sickle cell disease, congenital heart disease, immunodeficiency, trach vent, et cetera, and they also excluded kids with an ill appearance or hemodynamic instability during that encounter.

They learned that 91.5% of their patients were fully vaccinated, five and a half percent were under vaccinated, and 3% were unvaccinated. Does that data match what you’ve seen and Yes, we don’t know the true scope of the problem. I. But I think perhaps a more important question is whether or not unvaccinated or unvaccinated children are more at risk for non-vaccine preventable illnesses.

Clearly they’re at risk for vaccine preventable illnesses ’cause they don’t have the vaccine. And so in this episode, I’m gonna focus mainly on children three to 36 months of age with fever for less than five days. And I will say that the approach to an unvaccinated febrile child may differ from fully immunized children due to an increased risk of occult bacteremia and invasive bacterial infections.

The child’s immune system matures both with and without vaccines. Maternal immunity wanes by about three to six months until 36 months to maybe five years. The adaptive immune system is still developing. And kids are less capable of mounting an effective response to encapsulated bacteria like streptococcus pneumonia.

Haemophilus influenza type B RIA meningitis. By age five, we have developed more robust natural immunity from subclinical exposures to bacteria cumulatively. And so as long as you have a working immune system and a spleen that does what it’s supposed to do, different pathogens become more relevant, so you lose risk to encapsulated bacteria and you’ll see more mycoplasma pneumonia, streptococcus pyogenes.

And others, and at least for the context of this episode, I’m gonna be talking about fever without a source. And now maybe we’re excluding fever for an hour, which we’ve all seen in the emergency department, but it really means. When a complete history and physical examination cannot identify a specific source of fever greater than 39 centigrade or 102.2 Fahrenheit in a previously healthy otherwise well-appearing child.

Now, that threshold for 39 degrees could also be extrapolated to 40 degrees, and it’s relevant to literature and both the pre PCV and HIB era and in the post PCV and HIB era. But for simplicity’s sake, and based on the evidence that we do have, I’ll set that threshold at 39 degrees Celsius for this episode.

These children are at risk for occult infection such as UTI bacteremia and occult pneumonia. However, the majority of children who are well appearing and have no identifiable source of infection do have a self-limited viral illness. And in all of these kids, you gotta assess vaccine status, travel history, sick contacts, any immune compromise, and any symptoms of localizable bacterial infection to evaluate the risk of serious illness.

So serious bacterial infection defined as any bacterial infection requiring medical intervention, but it may not invade sterile sites. It’s like a UTI pneumonia skin and soft tissue infections like cellulitis and abscess. An invasive bacterial infection is a subset of serious bacterial infection where the bacteria gets into sterile body sites like blood and CSF.

It’s bacteremia, meningitis, osteomyelitis, septic arthritis, and. Let’s be honest, fever is still the most common complaint for infants and children brought to the ed. It’s greater than 6% of all ED visits. Most of these kids under 36 months will have some clinically apparent source of infection, even like a obvious URI or otitis media, and about one out of five of these children though a source cannot be identified during the h and p.

Certainly any child who’s ill appearing or has unstable vitals should be managed for presumed sepsis or septic shock, and that’s not the focus of this podcast episode in well Appearing Children with Fever. The main goal is to determine the risk of a clinically occult bacterial infection. I. So with that, let’s run through a few of these common bacterial infections.

So let’s start with urinary tract infections. So this is the most common occult bacterial infection in febrile infants and young children. And children under the age of two. Fever may be the only symptom. The prevalence is roughly eight to 10% in young children with fever. Greater than 39 Celsius. Risk factors include age, female sex circumcision status.

You should definitely use UTI calc. To help estimate the risk and the presence of another infection, like URI. Acute otitis media or gastro doesn’t completely rule out UTI, but in select scenarios like bronchiolitis with RSV, it does reduce the risk a bit. Females, three to 24 months with fever greater than 39 and no source, the risk could be as high as about 5%.

Uncircumcised. Males with high fever and no source probably have a similar risk to females, but circumcised males have a risk of 2% or under. You should also think about testing if there’s been fever for greater than 48 hours. If there’s history of UTI or any known GU anomaly, even like hypos, SPADs, and you can cath, you can clean catch, you can use the quick wee maneuver or even a super pubic aspiration which parents don’t like.

Alright, let’s talk about occult bacteremia. And honestly, when we talk about this topic, it’s the thing that we worry the most about. It’s the presence of bacteria in the blood of a febrile, well appearing child in the absence of an identifiable focal bacterial source of infection. So in the pre HIB and Prevnar era, this was like three to 11% of febrile children.

Streptococcus pneumonia made up 73 to 90% of these, and HIB made up eight to 22%. Hib was way more likely to cause meningitis. In fact, in 5% of bacteremia, kids with hib, they had meningitis. Really high rate. In the post vaccine era, the rate of occult bacteremia is. Point two five to 1%, so it’s less than 1%. A third of these are e coli.

A third are non-vaccine serotype, streptococcus pneumonia, and the other third are staph aureus, salmonella species, RIA meningitis, and strep pyogenes. Interestingly, both then and now, 95% of occult bacteremia is caused by strep pneumo resolve without IV antibiotics. These are all well appearing kids in which this happens, so we actually probably never know that some of these kids have it.

There’s a higher risk of occult bacteremia in children younger than four months of age, children with high fever, 39 or 40, and unvaccinated, and we’ll talk about labs in a little bit, but elevated white count A and C procalcitonin band count. These are all things that can be used to assess the risk. In preparation for this episode, I had the pleasure of talking to some folks that practiced in the pre HIB and Prevnar vaccine era, and what they told me was interesting.

They said that. Ultimately you could reduce a kid’s fever and that still didn’t reduce the risk of them having bacteremia. So they still had to work these kids up. But if the kid looked great after they responded to Antipyretics, well, they probably didn’t have meningitis. I. And so I alluded to this a couple minutes ago, but, uh, let’s talk about lab characteristics for oc cult bacteremia in the post vaccine era.

Let’s start with the CB, C and differential. And yes, we all know that CBC is not a good indicator of whether the child has a bacterial infection or not, but in this specific population, based on the available research, a white blood cell count greater than 15,000 does have a sensitivity of 72%. And a specificity of 55%.

This is based on one study from Hertz in, uh, pediatric infectious disease, and in their study though, the rate of a true positive blood culture was 1.6% and the contaminant rate was 1.8%. Interesting. A NC per Cooperman, etal and Annals of Emergency Medicine in 1998 of greater than 10,000 was a slightly better indicator and absolute band count of greater than 1500.

It’s also been suggested. None of these are perfect. So what about procalcitonin? And I know it’s not available everywhere, but it probably does have a better. A test characteristic than white blood cell count and a NC. Generally, the threshold is set at 0.5 nanogram per milliliter, but some sites suggest the threshold of greater than two and trella in the expert.

A review in of anti infectious therapy journal in 2017 noted that it had a sensitivity of 82%, specificity of 86%, and a positive likelihood ratio of six. And Van den Bruel in BMJ 2011 found procalcitonin to have better specificity than white blood cell count. Now let’s talk about pneumonia. So most children but bacterial pneumonia have some sort of abnormality.

On exam. In pro-vaccine era studies, 20 to 40% of three to 36 month old with fever greater than 39, and no clinical evidence of pneumonia, but with a white blood cell count greater than 20,000 actually had low bar or segmental pneumonia on a chest x-ray. In a study published in pediatric emergency care in 2009, Rutman and colleagues in a retrospective cohort of children less than five found that in comparison, occult pneumonia was identified more often.

Pre PCV. Then post PCV, so about 15% to 9% in kids younger than two, though the rate was higher. Pro-vaccine era, 17% and post vaccine era at 10%. So in the UN or under vaccinated kid with a temp greater than 39. If you get a white blood cell count and it’s greater than 20,000, you should get a chest x-ray, even if the kid has a normal lung exam.

And now let’s talk about blood cultures and. How many of you have heard from a nurse? Well, while, I’m getting the line. Why don’t I just draw a blood culture? So it’s either okay in these children to send it right away or to hold it until you get the labs back. And I think I would consult local practice variation, um, and what your colleagues do and the risk of contamination will not increase while the blood culture sits if it was obtained correctly.

And every hospital’s lab is different, but some of the bacteria that are considered common contaminants include bacillus. corynebacterium, cutie bacterium acnes, which was p acnes and micrococcus. Other contaminants include staphylococcus epidermis and the reins group. As long as the patient doesn’t have any risk of endocarditis, any other bug that grows.

We’re talking staph aureus, strep pneumonia, strep pyogenes, enterococcus, e coli. These are all probably true pathogens. Let’s say a blood culture is sent and then it comes back positive. So these kids should, in most cases, especially if it’s suspected to be a real pathogen, be reevaluated in the emergency department.

If kids are febrile at reevaluation, there’s a 40% chance of persistent bacteremia. And if they’re ill appearing about a one in 25 or 4% chance of meningitis. So these kids, if they’re ill appearing in febrile still, they need a full sepsis evaluation plus an LP iv antibiotics and admission. I. If they’re afebrile reevaluation, probably only about a 9% chance of persistent bacteremia.

And though we don’t know the exact numbers, that risk might be a little bit higher in unvaccinated children. So you can repeat the blood culture in labs and these well appearing kids, but you don’t necessarily have to tap them a positive blood culture for nisia meningitis, HIB gram-negative rods, or other pathogens.

Well, these always deserve a full sepsis workup. LP IV antibiotics and admission. If the kid’s afebrile and well appearing and they’re more than three months of age and they’re positive for e coli or staph aureus, they might not need an LP consult your local practice variations. Um, and any kid with group B streptococcus bacteremia, who’s three to six months of age definitely needs an LP and admission, and that only scratches the surface.

Admittedly, um, this can be a complex topic, so I would consult your local ID recommendations and hospital practice to determine what you should do based on what grows in your culture. I think now that we’ve talked about occult infections in some of the labs, you may be wondering, broadly speaking, do UN or under vaccinated children actually have more stuff done to them in the ed?

And the answer is probably, but we actually don’t know the broad answer. And so going back to that original study from Indiana, these kids that were. Not fully immunized, so UN or under vaccinated, were 83% more likely to get an intervention and 99% more likely to receive an antibiotic prescription, a discharge.

So this included all sorts of interventions, like blood testing, urine studies, chest radiographs. So ask yourself, what do you do if a kid is on or under vaccinated? Has a fever greater than 39, and is three to 36 months of age, are you working ’em up? What do your colleagues do? Do you have a practice guideline where you work?

In fact, is there a consensus guideline for the management of the UN or under vaccinated child with fever? And the answer to that unfortunately is no. No, there is not. Not from the A A P, not from the Infectious Disease Society of America, not in Red Book, not anywhere. So I’m gonna suggest one possible way to work these kids up with the caveat being that again, there’s no consensus, so.

For a child with fever greater than 39 degrees centigrade, who is well appearing, but unvaccinated or under vaccinated, who is between three to 36 months of age, you might want to consider getting procalcitonin CBC with differential urinalysis and urine culture if they meet the risk factors. And again, I would use UTI calc for that.

Any viral detection assays that you deem necessary. And you can draw blood culture and send immediately or send after the procalcitonin or CB, C results. So if the white blood cell count is greater than 20,000, regardless of the physical exam, you should get a two of you chest x-ray to assess for occult pneumonia.

If the procalcitonin. Is greater than 0.5. The white blood cell count is greater than 15,000. The a NC is greater than 10,000 and or the absolute band count is greater than 1,500. Then you should send the blood culture if you haven’t already done so and give empiric antibiotics against streptococcus pneumonia.

For most patients, this should be ceftriaxone 50 milligram per kilogram intramuscular. This depot version of antibiotics will provide coverage for 24 hours. It’s not the same as giving an IV dose. So yes, this is an IM dose. If they have an allergy to cephalosporins, you can give Clindamycin 10 milligram per kilogram iv followed by the first oral dose.

Eight hours later. Add UTI. Treatment is warranted based on your testing. If all of those labs. Are below those thresholds, then antibiotics are not recommended unless the urinalysis says otherwise. So after the labs are back, you reassess the patient. Are they well appearing? Are they well hydrated and demonstrating good oral intake?

Do they have a parent, guardian or caregiver that has no significant social barriers and. Can they follow up with their primary care doctor or at your facility within 24 to 48 hours? If yes to all of those, you can send them home. If not, eh, you should probably admit them to the hospital. I. Now again, this is just one way to consider working up the unvaccinated or unvaccinated child age three to 36 months of age, who is well appearing with fever greater than 39 degrees Celsius for less than five days.

This is not the official recommendation of my hospital or any that I know of, and I hope this inspires you to develop your own practice patterns and perhaps more importantly, have conversations locally where you work about better defining. How we evaluate and manage these children because unfortunately.

Their ranks are increasing. Well, I hope you found this episode on the approach to the unvaccinated and unvaccinated child with fever in the ed thought provoking. I hope it helps sharpen your thinking and clinical decision making and inspires you to have conversations locally about your practice patterns in these vulnerable children.

If you enjoyed the episode, be sure to like, subscribe, leave a review wherever you get your podcasts. Billy helps other folks find the show. You got feedback. Send it my way. I’ll take it over social media. I’ll take it via comments. I’ll take it via email, as always, for PEM Currents: The Pediatric Emergency Medicine Podcast, this has been Brad Sobolewski.

See you next time.