Optimizing fever management in pediatric emergency medicine: pathophysiology, diagnostics, and evidence-based strategies

Abstract

Fever is a prevalent clinical manifestation in pediatrics, representing a significant proportion of emergency department (ED) visits worldwide. While fever is often benign and self-limiting, it can also indicate life-threatening infections requiring immediate intervention, particularly in neonates and immunocompromised children. This comprehensive review delves into the intricate pathophysiology of fever, exploring its dual role as a protective immune mechanism and a potential physiological risk. It critically examines diagnostic challenges, evidence-based management strategies, and global disparities in fever treatment. Special emphasis is placed on parental perceptions, the overuse of antipyretics, and the emerging role of artificial intelligence in fever diagnosis. Future directions include refining diagnostic biomarkers, implementing digital health tools, and advancing antimicrobial stewardship to curb antibiotic resistance. By improving clinical decision-making and public awareness, this review aims to optimize the management of febrile children worldwide and enhance patient outcomes.

Introduction

Fever is a common clinical sign, defined as a body temperature of 100.4 °F (38.0 °C) or higher. Experts have called for a reevaluation of this strict cutoff, as the body’s ability to regulate temperature varies with age—especially in infants and neonates [1, 2]. Additionally, the method used to measure body temperature should be considered, as readings can vary depending on the measurement site. The most common sites include oral, axillary, rectal, and tympanic [3, 4].

In children, fever plays an important role in diagnosing or ruling out many medical conditions. While elevated body temperature is most often caused by infection, non-infectious causes should also be considered. Examples of non-infectious etiologies include Kawasaki disease, heat stroke, autoimmune diseases such as systemic lupus erythematosus, and malignancy-induced fever. Kawasaki disease should be considered in pediatric patients, especially when prolonged, unexplained fever is accompanied by lymphadenopathy [5]. Heat stroke, another serious condition, can lead to rapid morbidity in children.

Fever accounts for approximately 20% of all pediatric emergency visits, with most cases due to self-limiting viral respiratory illnesses [6]. Although many febrile children present with benign viral infections, fever in infants under three months of age may require urgent medical attention [7]. Thus, elevated body temperature remains a critical diagnostic tool in pediatric emergency care [7].

While fever is often a harmless symptom, parents commonly experience anxiety when children of any age develop even a slight elevation in body temperature. Observing changes in the pattern or severity of the fever—particularly the emergence of new symptoms—can intensify this anxiety, causing parents to question their knowledge and caregiving skills, ultimately exacerbating feelings of panic [8]. As a result, many parents respond aggressively to fever: 85% administer antipyretic medication before the child’s temperature reaches 38.9 °C, and 68% resort to sponging before the temperature hits 39.5 °C [9]. Although antipyretic use is appropriate in many cases, it is often accompanied by emergency department visits driven more by a need for reassurance than by clinical necessity [10].

Fever, while primarily a symptom of an underlying illness, can also lead to complications—ranging from febrile seizures in young children to severe dehydration if appropriate supportive care is not provided. In cases of viral illness, fever plays an important protective role by enhancing immune function and aiding in viral clearance. Such cases can often be identified through a careful history and physical examination. However, the non-specific nature of fever frequently leads to unnecessary hospital admissions and inappropriate antibiotic use, particularly in young children. This overuse contributes to the development of antimicrobial resistance and increases the risk of long-term health consequences associated with early antibiotic exposure [11]. Thus, it is essential to distinguish cases that require urgent medical attention from those that do not, and to provide appropriate reassurance and guidance to caregivers.

Many parents turn to search engines to obtain medical information when their children are unwell, particularly in the context of fever [11]. A lack of accurate knowledge and understanding contributes significantly to caregiver stress and anxiety. Pediatric healthcare providers have a unique opportunity to educate families on the role of fever in illness, when to seek emergency care, and when watchful waiting is appropriate [12]. Although pediatricians often attempt to address fever-related concerns during sick visits, only 38% discuss the potential risks and management of fever comprehensively [13]. Improving parental education about when to seek emergency care for febrile children could significantly reduce unnecessary visits to the emergency department.

This review aims to explore the pathophysiology of fever, the diagnostic challenges associated with pediatric fever, and the global strategies used in its management. It will also address controversies in fever care and highlight evidence-based approaches, while discussing future directions for improving the management of febrile children.

Pathophysiology and protective roles of fever

An adaptive reaction, fever fortifies the immune system, especially the innate arm. Pyrogens, or compounds that cause fever, are released when a person is exposed to an infectious agent. Pyrogens can be endogenous, such as cytokines like tumor necrosis factor-alpha (TNF-a), interleukin-1 (IL-1), and interleukin-6 (IL-6), or exogenous, such as bacterial endotoxins. The hypothalamus is stimulated by these chemicals and raises the body’s set-point temperature [14].

Increased production of pro-inflammatory cytokines is one important immunological boost brought on by fever. High temperatures maximize the activity of neutrophils, macrophages, and dendritic cells. These immune cells are essential for phagocytosis, antigen presentation, and the generation of reactive oxygen species in the fight against infections. Additionally, fever increases the cytotoxicity of natural killer (NK) cells, which hunt down and eliminate cancerous or virus-infected cells. Furthermore, fever stimulates the production of heat shock proteins (HSPs), which improve antigen presentation to T cells and shield cells from harm caused by stress [14, 15]. This whole process is illustrated in Fig. 1.

Fig. 1.

Pathophysiology of fever: immune and systemic responses

Pathogens are directly inhibited by fever because it creates an environment that is not ideal for their survival and reproduction. Numerous bacteria and viruses have developed to flourish in the limited temperature range of the host’s typical body temperature, which is about 37 °C. These infections’ enzymatic and structural stability are weakened by rising temperatures, which disrupts their capacity to replicate [15].

For instance, research has shown that high body temperatures hinder the development of bacteria such as Streptococcus pneumoniae and Escherichia coli and decrease the reproduction efficiency of influenza viruses. Fever also increases the sequestration of iron and zinc by proteins like metallothionein and ferritin. Bacterial growth depends on these micronutrients, and pathogen growth is inhibited during fever due to their decreased availability. This process, called nutritional immunity, demonstrates how fever can stifle microbial activity in an indirect manner [15].

Fever has preventive functions, but it also poses some physiological hazards, especially if it lasts a long time or is too high. Febrile seizures, which affect 2–5% of infants between the ages of 6 months and 5 years, are among the most worrisome complications in young children. Although these seizures are usually benign, caregivers may experience severe anxiety as a result. Rapid temperature escalation is believed to be a key factor in febrile seizures, while the precise process is yet unknown [15, 16].

Dehydration is another risk in fever. If fluid intake is inadequate, elevated body temperatures can cause hypovolemia by increasing insensible water loss through sweating and evaporation. This is especially problematic for young children, the elderly, and people with underlying medical issues. Because the basal metabolic rate rises by around 10–13% for every degree Celsius that body temperature rises, a prolonged fever also causes metabolic stress. Heart and respiratory disorders are among the underlying problems that may be made worse by this metabolic load [17].

Another danger is severe hyperthermia, which is characterized by a body temperature higher than 40 °C (104 °F). The body’s thermoregulatory systems may malfunction in certain situations, resulting in protein denaturation, cellular damage, and multi-organ failure. Hypothermia, which is linked to poor prognoses, can occur when the body is unable to develop a sufficient febrile response in some severe diseases, including sepsis [18].

The hypothalamus, in particular the preoptic area, is responsible for the tightly controlled regulation of body temperature, integrating signals from peripheral and central thermoreceptors to maintain homeostasis. Pyrogens cause fever by inducing the hypothalamus to produce more prostaglandin E2 (PGE2), which raises the set-point temperature and causes physiological responses like shivering, vasoconstriction, and increased metabolism to generate and conserve heat. However, in some situations, the thermoregulatory mechanisms can malfunction, such as in cases of severe infections like bacterial meningitis or septic shock, where excessive cytokine release can result in dysregulated temperature control, leading to hyperthermia; similarly, prolonged exposure to high environmental temperatures or intense physical activity in hot climates can overwhelm the body’s cooling mechanisms, resulting in heatstroke [19, 20].

Fever is a multifaceted physiological reaction that serves to both defend the host and fight off infections. New modalities such as the Neutrophil to Lymphocyte Ratio (NLR) and Monocyte distribution width (MDW) may enable clinicians to accurately determine when it’s important to intervene in cases of fever [21, 22].

Toll-like receptors (TLRs) on immune cells recognize pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs), triggering the release of pro-inflammatory cytokines such as IL-1, IL-6, and TNF-a. These cytokines accumulate and promote the synthesis of CRP in hepatocytes as part of the inflammatory response. IL-1 and IL-6 act on the hypothalamus particularly the preoptic area, where they stimulate the production of prostaglandin E2 (PGE2). PGE2 binds to the hypothalamic receptors raising the thermoregulatory set point. In response to the elevation of the set point, the body perceives its current temperature as too low and activates physiological processes to conserve and generate heat to meet the new target temperature via peripheral vasoconstriction and shivering. Several metabolic changes occur as an effect such as increase in heart rate & respiration. After the infection is resolved, cytokine levels decline, the set point normalizes, and mechanisms like sweating and vasodilation help dissipate heat, returning the body to homeostasis.

Diagnostic challenges in emergency settings

Reliable clinical indicators for evaluating fever

When a young child presents to the emergency department (ED) with a fever, various clinical signs can be assessed to help determine the underlying cause. These signs may range from mild to severe. Key indicators such as poor feeding, irritability, and an elevated respiratory rate can point to different etiologies responsible for the inflammation or infection causing the fever. A thorough history and physical examination are essential for identifying the potential source of the fever.

For example, patients presenting with an increased respiratory rate, cough, or other respiratory symptoms may have a lung infection. Bushra et al. reported that, in their pediatric ED, bronchopneumonia was diagnosed based on clinical signs of respiratory distress—specifically tachypnea, chest retractions, and crackles on auscultation—supported by chest X-rays showing bilateral patchy infiltrates [23]. Similarly, gastrointestinal symptoms such as nausea, vomiting, diarrhea, and increased bowel sounds, when accompanied by fever, may indicate a gastrointestinal infection. In the same study, patients were diagnosed with acute gastroenteritis (AGE) based on a history of loose, watery or mucoid stools (with or without vomiting), fever, and clinical signs of dehydration [23].

In young infants, fever accompanied by poor feeding and irritability may raise concern for meningitis. Thus, clinical signs are crucial for narrowing down the body system likely responsible for the fever. Physicians often rely on established clinical guidelines for managing febrile infants, which incorporate symptoms with high sensitivity and negative predictive value to guide further diagnostic or treatment decisions [24]. Relevant laboratory tests and imaging studies are then used to confirm specific diagnoses.

While clinical signs and symptoms are critical tools in evaluating febrile children, they cannot reliably distinguish between viral and bacterial infections. This is especially relevant in young infants, who have a higher risk of bacterial infections than older children, but often present with subtle or nonspecific symptoms. In such cases, clinical assessment alone is generally insufficient to rule out serious bacterial illness [12].

Table 1 summarizes key clinical indicators that may help differentiate viral from bacterial causes of fever in children presenting to the ED.

Table 1.

Differentiating bacterial and viral fevers: key indicators

Feature	Bacterial Infection	Viral Infection
Onset and Duration	Sudden onset; prolonged (>3–5 days)	Gradual onset; resolves in 3–5 days
Fever Pattern	High-grade (>102 °F–39 °C), persistent	Low to moderate-grade (< 102 °F–39 °C), intermittent
General Appearance	Toxic, lethargic, or ill-appearing	Non-toxic, alert, playful between fevers
Associated Symptoms	Localized symptoms	Generalized symptoms
Lymphadenopathy	Localized, tender, or large nodes	Generalized, non-tender lymphadenopathy
Response to Antipyretics	Partial or minimal	Often good response
White Blood Cell (WBC) Count	Elevated (>15,000/µL), neutrophilia	Normal or mildly elevated, lymphocytosis6
C-Reactive Protein (CRP)	Elevated (>40–50 mg/L)	Normal or mildly elevated
Procalcitonin	Elevated (>0.5 ng/mL; >2 ng/mL if severe)	Normal or mildly elevated (< 0.5 ng/mL)
Blood Culture	Often positive	Usually negative
Viral PCR or Serology	Negative	Positive
Chest X-ray	Focal consolidation	Diffuse interstitial or peribronchial infiltrates
Urinalysis	+ Nitrites, leukocyte esterase	Normal or mild pyuria
CSF Analysis	Neutrophil-predominant pleocytosis, low glucose	Lymphocytic pleocytosis, normal glucose

Common diagnostic tools and their limitations

While clinical signs and symptoms are crucial for decision-making in the treatment of febrile patients, additional diagnostic tools are often necessary to reduce uncertainty and confirm the underlying cause. In one study involving febrile children diagnosed with urinary tract infections (UTIs), it was found that although individual signs and symptoms were helpful, they were not sufficiently accurate for definitive diagnosis [25]. Thus, diagnostic tools tailored to each body system are essential in evaluating febrile children.

For example, when a patient presents with fever and an erythematous oropharynx, a rapid strep test is commonly used to evaluate for streptococcal pharyngitis. However, due to the relatively high false-negative rate of rapid strep tests, a throat culture may also be performed. Unfortunately, cultures take several days to produce results, limiting their utility in urgent clinical decision-making.

Similarly, if a febrile child presents with signs such as dysuria and increased urinary frequency, a UTI must be considered. In such cases, a urinalysis serves as a useful initial diagnostic tool. However, in patients with recurrent UTI symptoms, urinalysis alone may not be sufficient. Approximately 30–40% of children with UTIs require additional imaging, as recurrent infections may be due to underlying conditions such as vesicoureteral reflux (VUR) [26]. Imaging is essential in these cases, as failure to identify VUR can lead to serious complications. Notably, around 14% of children listed in the end-stage renal disease registry had VUR as a contributing cause [26]. Therefore, in children with recurrent UTIs, imaging studies—such as a voiding cystourethrogram (VCUG)—are necessary to guide appropriate treatment and prevent long-term complications. Simple diagnostic tools like urinalysis may not be adequate in these cases.

Furthermore, children presenting with fever, irritability, poor appetite, and reduced fluid intake may exhibit signs that suggest a viral illness. However, many of these children are hospitalized while awaiting blood culture results, which can take several days. During this period, patients may receive empiric treatment, leading to unnecessary hospital stays, exposure to antibiotics, and increased healthcare costs, which cause harm to patients [27]. In their study, Thuler et al. determined that false positive blood culture results in workup of fever in febrile children result in harm, thus clinical judgement and experience should take precedence in fever workup [28].

Therefore, while diagnostic tools are vital in evaluating febrile children, they also have limitations. Overreliance on lab tests and imaging may contribute to overtreatment, patient harm, and increased financial burden. A more balanced and evidence-based approach is needed to optimize care for febrile children.

Figure 2 illustrates a clinical guide for approaching fever in the emergency department to minimize unnecessary investigations and admissions for children less than 3 months.

Fig. 2.

Diagnostic steps for the febrile child < 3 months in the ED

The role of imaging and lab tests in identifying serious infections

For febrile children with suspected severe infections, further laboratory tests and imaging must be conducted. The initial laboratory test for children with suspected infections is a CBC. An elevated WBC can suggest an infectious cause of fever in children, particularly as the predominance of either neutrophils or lymphocytes further specifies the type of infection a patient presents with. Neutrophilic predominance may indicate bacterial infections, whereas elevated lymphocytes may suggest viral or fungal infections. Additionally, specific biochemical and hematological biomarker tests (including serum C-reactive protein [CRP] and procalcitonin [PCT]) are utilized to guide the presumptive aetiological diagnosis and management in young patients presenting with fever without a source [29]. Often, patients under 2 months of age who present with fever of unknown origin may require a lumbar puncture as a more accurate diagnostic test to assess for meningitis, an infection of the meningeal layer of the brain. The results of these tests will guide treatment, as they can identify elevations in neutrophils and lymphocytes, as well as the roles that glucose and protein levels play in different types of infections.

Furthermore, apart from lab markers, imaging plays a vital role in diagnosing patients who present with fever and non-specific symptoms or even no symptoms at all. A study on patients with fever of unknown origin concluded that while infections may be more common in these cases, other aetiologies such as malignancies or inflammatory diseases must also be considered [30]. Some of these lab markers and their role in identifying causes of fever in children is summarized in Table 2. Similarly, imaging or lab tests can help identify types of infections or inflammation. For instance, a patient presenting with fever and an abnormal gas pattern, air-fluid level, or soft tissue mass observed on an abdominal X-ray could suggest a possible abscess, whereas inflammation of the appendix could indicate appendicitis. Each condition requires different treatment modalities; however, they can all present solely as a fever of unknown origin without any other symptoms. Likewise, a chest X-ray should be conducted to determine the cause of a respiratory infection. Specific findings noted on an X-ray provide additional insights into whether the infection is bacterial or viral, which can help guide treatment. Occasionally, basic radiographic studies may not suffice to establish such diagnoses, and more advanced imaging, such as a PET scan or full body CT scan, becomes essential for confirming or ruling out a diagnosis in cases of febrile children with concerns of possible malignancies or inflammatory disorders [30].

Table 2.

Biomarkers of acute febrile illnesses in children and their diagnostic utilities:

Challenges in identifying severe infections in febrile children

Identifying the causes of infection in febrile children presents multiple challenges. Young infants often experience temperature dysregulation due to an immature inflammatory cascade, which may occasionally manifest as hypothermia rather than the typical elevated temperatures observed. Particularly, newborns especially those with low birth weight or prematurity are at increased risk for hypothermia, due to factors like a large surface area in relation to their body weight, decreased amount of fat for insulation and heat production, thin skin, and immature thermogenesis [24]. Therefore, hypothermic infants have been incorporated into febrile infant pathways or undergo full sepsis evaluations with blood, urine, and cerebrospinal fluid (CSF) cultures [24].

In addition, young children have difficulty vocalizing specific symptoms and are unable to present with generic chief complaints such as headaches, sore throat or even abdominal pain. This makes it particularly challenging when narrowing down specific diagnoses. Infants under 3 months of age presenting with fever are at risk of invasive bacterial infections, namely bacteremia and meningitis which can be fatal if not treated adequately. As they often present with non-specific symptoms and signs, risk stratification is challenging for even the most experienced clinicians [14]. The most common presentations for unwell children are often non-specific signs such as increased fussiness, poor feeding, or irritability, which can be misdiagnosed as a viral illness despite actually being a serious infection. Thus it is extremely important to use a combination of specific diagnostic tools, lab tests and imaging in order to provide adequate care to febrile children.

Management controversies in the emergency department

The management of febrile children in the Emergency Department (ED) remains a subject of ongoing debate. The use of antipyretics, the timing of treatment versus observation, criteria for hospitalization, and variations in management practices across different regions are some of the key areas where controversies persist. These controversies stem from differing interpretations of the available evidence, clinical experience, and the context in which healthcare is provided. This section will discuss the evidence for and against the use of antipyretics, the decision-making process for determining when to observe versus treat febrile children, the criteria for hospitalization, and how management practices vary globally.

Antipyretic use: evidence for and against

Antipyretics, such as acetaminophen and ibuprofen, are commonly used to reduce fever and improve comfort in children. Antipyretics are often administered to children with fever by pediatricians primarily due to fear of convulsions, to make the child comfortable, and to prevent brain damage [31, 32]. Lowering the body’s temperature may help reduce symptoms like irritability, malaise, and poor feeding, commonly associated with fever. Given the rarity of convulsions caused primarily from fever [9], the clinical benefit of antipyretics, beyond comfort, remains controversial [31]. Use of antipyretics also has no effect on reoccurrence of febrile seizures [31].

While antipyretics have the benefit of may be to reducing discomfort, only about 25% of pediatricians agree to let a sleeping child with fever be [32]. Studies show that children who receive antipyretics report feeling better, even if their body temperature is not normalized [9].

Achieving comfort is important in the emergency setting where the immediate goal is often to comfort the child and alleviate distress. Nevertheless, evidence is inconclusive on the use of antipyretics in children presenting with fever [32].

However, there are concerns that antipyretics may mask symptoms of serious infections, leading to delayed diagnosis and treatment. Fever is an important indicator of infection, and its reduction may impair the clinician’s ability to assess the severity of the illness [33]. Furthermore, there is limited evidence supporting the notion that antipyretics improve clinical outcomes, such as reducing the duration of illness or preventing complications [31, 34]. In fact, some studies suggest that antipyretic use may have little to no impact on the course of febrile illnesses [35]. Another consequence is the overuse of antipyretics which can lead to toxicity [32]. Table 3 summarizes the risks and benefits of antipyretic use.

Table 3.

Antipyretic use: risks and benefits

Aspect	Risks	Benefits
Acetaminophen	Risk of hepatotoxicity with overdose or frequent supratherapeutic dosing.	Effective in reducing fever.
	Rare cases of asthma exacerbation.	Onset of effect within 30–60 min.
		Reduces fever-related discomfort.
Ibuprofen	Risk of gastritis, gastrointestinal bleeding, or ulcers.	Longer duration of fever reduction compared to acetaminophen (6–8 h).
	Possible nephrotoxicity, especially in dehydrated or medically complex children.	Effective at reducing fever.
	Risk in younger infants (< 6 months) due to developmental renal differences.	Reduces discomfort associated with fever.
	Possible association with varicella-related invasive group A streptococcal infections (inconclusive evidence).
Combination Therapy	Increased risk of dosing errors and adverse outcomes.	May lower fever more effectively in some cases.
	Complexity of dosing regimens could lead to misuse.	Potential to improve comfort in some children when properly administered.
	May promote “fever phobia” in parents, encouraging excessive treatment.

Observation vs. immediate treatment: when to act

When a child presents with a fever, the clinical decision-making process should be guided by an assessment of the severity of the fever and the presence of red-flag symptoms. In many cases, observation may be appropriate, especially for children with mild fever and no associated red-flag features. For example, a child with a low-grade fever and no other concerning symptoms may not require immediate intervention. Observation in this context allows for the monitoring of any evolving clinical signs.

A critical factor in the decision to observe is the child’s age. In infants under three months of age, a more cautious approach is warranted due to the risk of serious bacterial infections such as sepsis or meningitis [33]. Infants in this age group should be closely monitored, as they are at higher risk for rapid deterioration.

Immediate treatment is required for febrile infants under three months, who are at increased risk of serious infections like sepsis or meningitis [35]. These infants typically require admission to the hospital and may be treated empirically with broad-spectrum antibiotics until a definitive diagnosis is made. In addition, children who present with signs of severe infection, such as respiratory distress, altered consciousness, or signs of dehydration, should be treated immediately.

In cases of high fever, persistent fever, or when a child presents with other systemic symptoms such as rash, lethargy, or vomiting, immediate treatment should also be considered. Immediate treatment might include the administration of intravenous fluids, antibiotics, or antiviral therapy, depending on the suspected etiology.

Criteria for hospitalization in febrile children

Hospitalization of febrile children is primarily considered when there is concern for serious illness, when outpatient management has failed, or when the child’s clinical status necessitates closer monitoring. The primary reasons for hospitalization include:

• Sepsis: Febrile children with signs of sepsis, such as tachycardia, hypotension, or altered mental status, should be hospitalized for aggressive treatment and monitoring.

• Dehydration: Severe dehydration that cannot be corrected through oral rehydration therapy requires hospitalization and intravenous fluids.

• Failed Outpatient Management: Children who fail to improve with initial outpatient management, or whose condition worsens despite treatment, should be admitted for further evaluation and treatment [31].

Age is a critical factor in the decision to hospitalize febrile children. Infants under three months are at a significantly higher risk for serious infections, and therefore, the threshold for hospitalization is lower for this group. In contrast, older children with mild fever and no signs of severe illness may be managed on an outpatient basis [31].

Global variations in management practices

Management practices for febrile children vary significantly across different parts of the world. In high-income countries, there is a strong emphasis on diagnostics, with advanced laboratory tests, imaging, and close monitoring frequently used to guide management [36]. In these settings, fever is often treated symptomatically, and diagnostic workups are conducted to rule out serious infections.

In contrast, in low-resource settings, where access to diagnostic tools and specialized care may be limited, management often relies more heavily on clinical judgment and the child’s presentation. In many low-resource settings, clinical features such as dehydration, lethargy, or poor feeding are used to guide decision-making [36]. The lack of diagnostic resources often leads to a more empirical approach to treatment, with broad-spectrum antibiotics being used in febrile children until a diagnosis is made. Due to the peculiarities of infectious sources and manpower in low-income settings, a management approach such as Table 4 can be used.

Table 4.

Simplified management protocols for low-resource settings for pediatric fever. Integrated Management of Childhood Illness (IMCI) strategy by the World Health Organization (WHO) provides comprehensive guidelines for managing pediatric fever in low-resource settings. This structured management guidelines emphasizes early risk stratification, empirical treatment where needed, and timely referrals to prevent severe outcomes. ICMI uses a color coded system to signify severity with pink: severe illness, yellow: moderate illness, and green: mild/no serious illness

The management of febrile children in the Emergency Department remains complex process that involves careful clinical assessment and decision-making. While antipyretics can improve comfort, their use should be balanced against the risk of masking serious infections. The decision to observe versus treat febrile children is largely based on age, clinical signs, and the presence of red-flag symptoms. Hospitalization is indicated for severe cases, particularly in infants under three months, and global practices vary based on available resources.

Special populations

Infants less than 3 months are challenging populations in diagnosis and management aspects when admitted to ED as febrile patients. Compared to other age ranges of children, febrile infants have a higher incidence of sepsis, meningitis and serious bacterial infection (SBI) [7]. That is why one of the guidelines of the National Institute for health and Care Excellence (NICE) recommends managing infants with fever in ED as having a high risk of serious bacterial infection (SBI) by admitting them, implementing laboratory procedures for diagnosis, and prompt administration of antibiotics empirically [37, 38]. This is useful in managing febrile infants and reducing morbidity and mortality; however, it causes overuse of antibiotics accompanied by the risk of developing any of their side effects in infants with no SBI.

Urinary tract infection is the most common infection among the SBIs in febrile infants and is attributed to 75% to 84% of SBIs [38]. In this context, the American Academy of Pediatrics advocates the necessity of performing urine analysis and urine culture for febrile infants with no localized symptoms before adopting the empirical antibiotic [39].

Among this age group, infants that are younger than 1 month are at higher risk and need closer management than those between 30 and 90 days. From this perspective, a cautious approach is followed in the diagnosis and management of febrile neonates. Regarding the appropriate diagnostic tools, blood and urine cultures, lumbar puncture for cerebrospinal fluid analysis, and complete blood count are adopted [38]. For management approaches, empirical administration of combinations of ampicillin and gentamicin or ampicillin and cefotaxime sodium or cefotaxime alone is used [38, 40].

Another challenging group is immunocompromised febrile children who suffer from the lack of recognizable signs and symptoms of infection except fever. They are more susceptible to being infected with SBI than others due to immune deficiency. That necessitates robust and quick care for this special group. Since the current diagnostic biomarkers can not be reliable enough to differentiate bacterial infection from viral one [41], this group is generally managed through the rapid administration of antibiotics empirically to avoid treatment failures [42]. In a meta-analysis study, it was shown that the procalcitonin test gives more reliable results compared to CRP in this special group. Additionally, the study showed that IL-6 and IL-8 are two sensitive tests that can differentiate gram-negative bacterial infections [43]. New promising diagnostic-specific tests have recently been introduced and need further research, such as host RNA biosignatures which have the advantage of high sensitivity and specificity [44].

The role of antipyretics in managing febrile seizures

The role of antipyretics in managing febrile seizures remains limited. While some evidence suggests they may reduce the recurrence of febrile seizures within the same fever episode, there is no robust evidence to support their efficacy in preventing seizures altogether. A systematic review of eight studies found limited support for the role of antipyretics in preventing recurrence within the same fever episode, with only one study demonstrating a significant reduction in recurrence rates [33]. However, no evidence supports their efficacy in preventing recurrence during distant fever episodes or in lowering fever during febrile episodes that lead to seizures. These findings align with previous research showing that antipyretic agents, including acetaminophen and aspirin, and adjunctive methods like sponge bathing, are ineffective in preventing febrile seizure recurrence [33]. Current evidence suggests that antipyretics should be used solely for symptomatic fever management, as they do not reduce the risk of febrile seizures [14]. Further research is required to assess the timing and conditions under which antipyretics might provide a benefit.

Reviews of prophylactic drug management in children with febrile seizures have consistently found no significant benefits of antipyretics in preventing seizures. However, weak evidence suggests a potential role for antipyretics in reducing febrile seizure recurrence within the same fever episode. Despite this, there is no evidence supporting their use for prophylaxis in preventing febrile seizures during distant fever episodes. As such, antipyretics should be used primarily for symptomatic fever management rather than seizure prevention [31]. Educating caregivers and healthcare providers on their limited role is crucial to set realistic expectations and promote evidence-based management [33].

Additional considerations in children with chronic conditions

For children with chronic conditions, fever evaluation can be complicated by their specific vulnerabilities, requiring tailored management strategies. Fever management in children with chronic illnesses requires a tailored approach due to their heightened vulnerability. Steele at el. Emphasized that immunocompromised Children have a significantly increased risk of severe infections, making early and thorough evaluations essential [42]. Conditions like cerebral palsy, cognitive impairment, and other disabilities introduce additional considerations such as reduced communication abilities, difficulty in evaluating symptoms, and increased susceptibility to infections [42]. Chronic illnesses may also affect immune function, mask typical symptoms, and increase the risk of complications like aspiration pneumonia, urinary tract infections, and dental infections. In one-third of cases, no cause for the fever will be identified In immunocompromised children [43]. Additionally, factors like malnutrition, dehydration, and medication side effects must be carefully considered when managing febrile episodes in these children [33]. A comprehensive approach that includes a review of the child’s medical history, specific risks, and close monitoring for atypical presentations is crucial for effective fever management. For children with chronic conditions, fever management becomes more complex.

Evidence-based emergency management

Under emergency circumstances, healthcare providers must be prepared to manage acute fever in pediatric patients even before determining its origin. However, the management approach can differ depending on whether the fever is of bacterial, viral, or non-infectious origin. Fevers caused by bacterial infections tend to be more severe than those from viral illnesses. Specifically, fevers exceeding 39 °C are more likely associated with serious bacterial infections (SBIs), while those reaching or surpassing 41 °C may indicate meningitis [45]. Nonetheless, a prospective study demonstrated that fever height alone is insufficient for infection risk stratification in children [46].

In clinical practice, bacterial infections are often suspected based on biomarkers from a complete blood count—such as elevated C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR)—or confirmed via cultures identifying the causative organism [47]. In suspected cases of sepsis or septic shock, empiric antibiotics are typically administered urgently, along with laboratory testing and culture collection. However, due to the growing antimicrobial resistance (AMR) crisis, immediate empiric antibiotic administration is no longer routinely recommended without sufficient diagnostic evidence [48]. When blood cultures are indicated, they should be drawn before antibiotic administration, particularly in high-risk populations such as immunocompromised or diabetic children [47].

In contrast, febrile children with viral infections may be managed with antivirals if a specific virus is identified. However, most viral infections in children are self-limiting and resolve more quickly than bacterial illnesses [49]. Fever may also be a symptom of non-infectious conditions such as malignancies, systemic inflammation, or connective tissue diseases like systemic lupus erythematosus and juvenile rheumatoid arthritis (JRA) [50].

While fever is a physiologic response that supports the immune system in clearing infections, very high temperatures can be harmful and warrant intervention [51]. Ibuprofen and paracetamol remain the only antipyretics approved for children, with proven safety and efficacy when used within recommended doses. In addition to pharmacologic treatment, non-pharmacologic approaches—such as ensuring adequate hydration and nutrition—are vital [7].

The urgency for diagnostic algorithms in the AMR era

With AMR emerging as a global health threat akin to a silent pandemic, there is an urgent need for diagnostic algorithms that can accurately distinguish bacterial from viral infections. In low-income settings, clinicians often initiate empiric antibiotics for 32–74% of febrile patients without diagnostic confirmation [52]. However, one study found that only 55% of pathogens were effectively treated empirically, while the remainder were mismanaged [53]. This highlights the need for improved diagnostics to guide treatment decisions.

Awareness campaigns promoting the use of diagnostic algorithms and point-of-care tests have already had a measurable impact, reducing antibiotic prescriptions in children under five by 9% [54]. Figure 3 illustrates global disparities in antimicrobial use for febrile children using a heat map.

Fig. 3.

Heat map and management practices of acute febrile illnesses in children across countries

Diagnostic algorithms can be categorized into three types:

1. Clinical diagnostics rely on healthcare providers’ ability to differentiate between bacterial and viral infections based on symptoms and physical signs. However, this method alone is insufficient due to variability in provider experience and disease presentation [53].

2. Pathogen-specific diagnostics have shown promise, particularly in diseases like malaria. Rapid diagnostic tests such as urine Lipoarabinomannan (LAM) for tuberculosis and antigen-based tests for dengue represent significant advancements [55, 56]. Yet, these tools still require improvements in speed, specificity, and affordability to reach full clinical utility.

3. Biomarker-based diagnostics involve indicators like procalcitonin and CRP, which are more elevated in bacterial infections. These tests are advantageous due to their ease of use, rapid turnaround time, and high sensitivity. Successful implementation in several countries has helped reduce unnecessary antibiotic use [57, 58].

The most effective diagnostic strategies integrate all three approaches—clinical assessment, pathogen-specific testing, and biomarkers—to guide appropriate management.

Preventive strategies and public education

To reduce the burden on emergency departments and minimize unnecessary visits, public health efforts should focus on prevention. For pediatric populations, vaccination is the cornerstone of disease prevention. Healthcare providers must adhere to national immunization schedules and stay updated on recommendations for newer vaccines, including those for seasonal illnesses like influenza, rubella, and COVID-19. Public awareness campaigns emphasizing undervalued vaccines—such as those for cholera and hepatitis B—can help improve vaccine uptake and public understanding.

Despite the availability of effective vaccines, diseases like tuberculosis continue to cause significant mortality due to underutilization. In response, the CDC and other bodies have updated their immunization guidelines to include additional vaccines, such as Haemophilus influenzae type b (Hib) [59]. Educational initiatives, including community lectures and informational materials, are also essential components of prevention strategies.

Risk prediction tools for febrile children in emergency settings

Children presenting to emergency departments with acute febrile illnesses may be at risk for progression to sepsis, septic shock, or even death. Early identification of high-risk cases is essential. The Pediatric Early Warning Score (PEWS) is a tool designed to predict deterioration in pediatric patients by scoring vital signs, clinical assessments, healthcare provider concerns, and patient history [60, 61]. Based on the score, clinicians can stratify patients by risk and determine the urgency of intervention.

PEWS systems may vary across countries and institutions based on local practices, patient populations, and targeted outcomes (e.g., ICU admission or mortality). A variant known as ED-PEWS (Emergency Department PEWS) has shown promise in high-income countries but still requires validation in low- and middle-income settings [62]. The ED-PEWS consists of a combination of physiological measurements that can be objectively obtained in the ED. It examines 3 systems: the CNS, respiratory and circulatory system with points ranging from 0 to 68. The complete ED-PEWS is shown in Table 5. Using a cutoff >10 had the best sensitivity in determing children who may require urgent iuntervention in the ED [63].

Table 5.

ED-PEWS=emergency department paediatric early warning score, adapted from Zachariasse et. al (2020)

Component	Variable	Points
General	Age
	0–4	0
	5–11	4
	12–16	6
Quick look	Decreased consciousness	14
	Increased work of breathing	12
Respiratory	Respiratory rate:
	<30	0
	30–39	3
	40–59	5
	=60	9
	Oxygen saturation (%)
	=98	0
	94–97	4
	88–93	9
	<88	15
Circulatory	Heart rate
	<100	0
	100–139	3
	140–179	6
	=180	9
		Total:

Additionally, AI-based prediction tools are emerging as powerful assets for risk stratification in emergency departments. These technologies can enhance decision-making under time-sensitive conditions by predicting patient outcomes such as ICU admission or mortality. However, the lack of high-performing tools in resource-limited settings highlights the need for focused development and validation efforts in these regions to reduce pediatric mortality and morbidity.

This figure provides a comprehensive analysis of fever etiology prevalence and associated management practices across a selection of countries globally.

Panel 1 presents a heat map illustrating the relative prevalence of various fever etiologies, including malaria, dengue, bacterial infections, viral infections, zoonotic diseases, and mixed etiologies. The intensity of color reflects the relative burden in each country, with darker shades indicating higher prevalence.

Panel 2 provides a bar chart depicting the prevalence of common fever management practices, categorized as follows:

• Antimalarial use: The administration of antimalarial medications as a primary treatment.

• Antibiotics: The use of antimicrobial agents targeting bacterial infections.

• Clinical diagnosis: Diagnoses based on symptomatic evaluation by healthcare professionals.

• Laboratory diagnostics: The use of diagnostic tools, such as blood tests and cultures, to identify the etiology of fever.

• Traditional therapies: Includes non-conventional practices rooted in cultural or indigenous traditions, such as herbal remedies and homeopathic treatments. These therapies are often utilized as complementary approaches to conventional medicine.

Global perspectives and low-resource settings

Fever is one of the most prevalent clinical complaints in the world and presents difficulties in environments with limited resources. These difficulties are frequently brought on by socioeconomic restrictions, cultural views of sickness, and restricted access to healthcare infrastructure.

Several reasons make it difficult to diagnose and treat fever effectively in settings with limited resources. One of the biggest obstacles is limited access to diagnostic tools. Many medical institutions in low-income areas rely on clinical judgment rather than sophisticated diagnostic tools. Lack of access to basic laboratory testing, imaging, and microbiological cultures frequently causes confusion in diagnosis and delays in determining the underlying cause of fever. Moreover, these issues are made worse by overworked healthcare systems. The quality of care for febrile patients is sometimes compromised by healthcare workers working in overcrowded, understaffed environments with inadequate pharmaceutical supplies [64].

Another important factor that delays access to care is socioeconomic constraints. Families are unable to get timely medical care because of poverty, remote location, and a lack of transportation. Families are further deterred from seeking medical attention until symptoms worsen by out-of-pocket costs. Antimicrobial resistance can also result from overtreatment, such as the needless use of antibiotics or antimalarials, or by relying only on clinical judgment in the lack of diagnostic tools [65].

In settings with limited resources, simplified clinical guidelines have shown to be a very useful tool. These recommendations are more practical for frontline healthcare professionals since they place a higher priority on clinical signs and symptoms than laboratory-dependent diagnosis. For example, the Integrated Management of pediatric Illness (IMCI) program of the World Health Organization offers evidence-based guidelines for treating common pediatric diseases, such as feverish conditions [66]. Lethargy, difficulty feeding, and fast breathing are examples of danger indicators that should be recognized in order to promptly send a patient to higher-level treatment, according to the IMCI method. Research has demonstrated that IMCI increases care efficiency and lowers child mortality [67]. Their usefulness is further increased by guidelines that are adapted to particular regional demands, such as those treating febrile infections that are endemic to Southeast Asia or sub-Saharan Africa. Furthermore, smartphone applications and other mobile health (mHealth) solutions are showing promise as platforms for distributing streamlined recommendations and offering decision help to medical professionals in remote locations [64].

In environments with limited resources, community health workers (CHWs) are essential to the management of fever. CHWs serve as a link between the public and healthcare institutions by becoming dependable members of their communities. For patients with fever, they frequently operate as the initial point of contact, evaluating symptoms, giving basic care, and deciding if a referral to a higher-level hospital is required. Along with frontline care, CHWs teach families how to spot warning signs of serious illnesses, how important it is to finish recommended treatments, and how to prevent diseases like malaria and mosquito net use. CHWs assist overworked hospitals and clinics by handling simple illnesses locally, freeing them up to concentrate on patients who are in severe condition. CHWs are trained and assisted with basic materials and streamlined standards [68].

Cultural beliefs and practices surrounding fever vary greatly across regions and have a significant impact on health-seeking behavior. For example, some cultures attribute fever to supernatural causes or traditional concepts of body imbalance, which lead families to seek traditional healers before considering biomedical care. Additionally, different communities have different approaches to fever treatment, with some prioritizing “letting the fever break” naturally and others believing in aggressively cooling the body with techniques like cold baths or compresses. These practices may delay or interfere with appropriate medical interventions, and cultural mistrust of formal healthcare systems can deter families from seeking medical care due to past negative experiences, communication barriers, or perceptions of high costs. Culturally sensitive health education campaigns can address these issues by combining local beliefs with evidence-based reforms [69].

A multimodal strategy that tackles obstacles to diagnosis and treatment, makes use of streamlined clinical guidelines, empowers community health workers, and takes cultural contexts into consideration is needed to manage fever in low-resource settings. Healthcare systems may lessen the cost of avoidable fatalities and enhance outcomes for patients with fever by customizing interventions to the particular requirements of these settings [70].

Future directions and controversial research gaps

As discussed earlier, it is crucial in the management of acute febrile illnesses in children to differentiate bacterial infections from non-bacterial ones. However, the diagnostic biomarkers lack full specificity and sensitivity, which might cause misleading results, especially in critically ill patients such as those with sepsis [70]. This highlights the need for novel biomarkers that have better performance, especially for special populations like neonates and immunocompromised febrile patients. One of these is Presepsin, a novel biomarker that is correlated with the pathophysiology of sepsis, which gives it the advantage of high specificity and sensitivity to bacterial infections [71, 72]. It is considered a promising biomarker to detect bacterial infections since it is promptly elevated in response to infection, in addition to its cost-effectiveness compared to blood tests and cultures [73]. Since presepsin has the advantage of not being affected by prenatal factors or gestational age, it is considered a good choice as a biomarker for neonatal sepsis compared to CRP and PCT [74]. In addition, it is used as an indicator of the good efficacy of the administered antibiotic [75]. In children, presepsin provides more specific and sensitive responses to bacterial infections than the commonly used biomarkers. Moreover, it possesses the ability to identify infection conditions in febrile children with neutropenia where other biomarkers are not reliable enough [76].

Another promising biomarker for febrile illnesses in children is the transcript host RNA signatures. It shows potential responses in differentiating bacterial infections from viral ones. It works through the analysis of the transcriptional biosignatures of RNA in the leukocytes of the host, which is why it has high accuracy and sensitivity [77].

The MeMed BV score is another promising diagnostic tool that has been clinically proven to be used in children. It can differentiate between bacterial and viral infections by analyzing the host’s immune response and evaluating the levels of specific proteins, such as C-reactive protein (CRP) and interferon gamma-induced protein 10 (IP-10). It is characterized by its rapid and validated results [78, 79].

FebriDx is a point-of-care diagnostic tool that can distinguish between bacterial and viral infections from a fingerstick blood sample. This provides a quick and easy method for examining various diseases. It mainly depends on assessing the levels of C-reactive protein (CRP) and myxovirus resistance protein A (MxA). It can be used in various healthcare settings, including emergency and primary care settings [80, 81].

Another potential future appears clearly with the development of artificial intelligence (AI) and its involvement in all life fields; it was expected that this highly developed technique would also have an impact on healthcare. One of the promising advanced technologies is Mobile health apps (health). They are advanced computational applications that serve the healthcare field in many ways. It can lead to a range of complications, such as kidney, liver, and heart failure, which can eventually lead to brain damage and death [82]. Increasing education is vital as these concepts may also help increase the number of children with a true serious infection to seek medical care rather than being neglected.

AI and machine learning techniques showed an advanced development in the early detection of febrile diseases at the community level. The Targeted Real-time Early Warning System (TREWS) is an example of clinical decision support tools that use AI and machine learning to detect the earliest stages of sepsis. TREWS provides continuous monitoring and analysis of electronic health data to identify patients at high risk of developing sepsis before the onset of clinical symptoms. A prospective multi-center study evaluating the efficacy of TREWS found a 4.5% reduction in mortality rate and improvements in outcomes [83].

Conclusion

In summary, fever in children serves as a critical physiological mechanism, aiding in the immune response to infections and providing a diagnostic pathway for various conditions. However, its significance is often misunderstood, contributing to widespread parental anxiety and unnecessary medical interventions. By enhancing parental education on fever’s protective roles and potential risks, healthcare providers can address misconceptions, reduce non-urgent emergency visits, and improve care quality. At the same time, identifying febrile children who require urgent intervention remains a diagnostic challenge, especially in infants and special populations. Advanced biomarkers and AI-driven diagnostic tools offer promising avenues for improving accuracy and reducing reliance on empirical treatments, thus mitigating the risks of antimicrobial resistance.

Global disparities in fever management underscore the need for tailored interventions, particularly in resource-limited settings where diagnostic capabilities are constrained. Integrated strategies involving clinical algorithms, community health workers, and culturally sensitive health education can enhance outcomes and alleviate the burden on healthcare systems.

Looking ahead, further research is essential to refine diagnostic biomarkers, evaluate the long-term effects of antipyretic use, and develop robust, accessible tools for fever management. Addressing these gaps will enable clinicians to optimize care for febrile children, balancing the protective benefits of fever with the imperative to prevent complications. As we continue to unravel the complexities of pediatric fever, fostering collaboration across disciplines and regions will be paramount in achieving equitable and effective healthcare for all children.

Abbreviations

CRP

C-reactive protein

PCT

Procalcitonin

SBI

Serious bacterial infection

ED

Emergency Department

IMCI

Integrated Management of Childhood Illness

UTI

Urinary tract infection

PEWS

Pediatric Early Warning Scores

AI

Artificial Intelligence

Authors’ contributions

MA is considered the first and fonding author. He proposed the project, wrote the protocol, screened an selected initial studies, participated in drafting of the article and reviewed and revised the manuscript. CDO is considered second author, he contributed to the conception, formulation, drafting of the article and reviewed and revised the manuscript. AP, EMA, RM, ME, CJO, SAZ, and EL participated in writing and revising the final manuscript. All authors approved the final manuscript as submitted.

Funding

No external funding received.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent to publication

Not applicable.

Competing interests

The authors declare no competing interests.