1. 1
Fever in Infants and Children:
Mohamed Abunada, MD
Department of pediatric Neurology
Al Rantisi Specialized pediatric Hospital

2. 2
Fever
• Fever is the most common pediatric complaint,
second only to routine care for clinic visits, and
the most common reason kids are brought to the
ER.
• 5-20% have no localizing signs on PE with no
history to explain the fever.
• The majority of kids with fever do not have a
serious illness, although a small percentage
harbor or may develop a serious bacterial
infection.

3. 3
‘True’ Fever
• Occurs when IL-1, IL-6 or other cytokines are
released from monocytes and macrophages in
response to infection, tissue injury, drugs, and
other inflammatory processes, increasing the
body’s set point. The anterior hypothalamus
maintains an inherent set point near 36ºC(98.6ºF).
• Normal circadian rhythm, which is highest(up to
2ºC) ~6pm and lowest at 6am. This accounts for
increased volume of ER visits that peaks in the
evening. Most true fevers follow this diurnal
pattern.

4. 4
‘False’ fever
• Does not directly increase the body’s set point.
• CNS disease that directly affects the hypothalamus--ICH,
infection.
• Diseases that increase the body’s production of heat--
hyperthyroidism, malignant hyperthermia,
salicylate overdose.
• Excess heat load--child left in a car or left next to a
heater for too long.
• Defective heat loss mechanisms--burns, heat stroke,
drugs that compromise blood flow and sweating
mechanisms.
• Normal causes of temperature elevation include physical
activity, ovulation, and environmental temperature.

5. 5
Malignant hyperthermia
• can follow intense muscle contraction
(cocaine overdose) or muscle metabolism
altered by drugs (neuroleptic agents) or
anesthetics.

6. 6
Heatstroke,
• Heatstroke, a potentially fatal febrile
illness, is caused by excessively high
environmental temperatures and failure of
physiologic body heat-losing mechanisms

7. 7
Fever
• does not always represent infection.
• Rheumatologic disease, inflammatory bowel
disease, Kawasaki disease, poisoning, and
malignancy also may present with fever.
• The varied manifestations of infectious
diseases frequently mimic rheumatoid
arthritis, lupus erythematosus, inflammatory
bowel disease, leukemia, and lymphoma

8. 8
Reliable Temperature
Measurement
• All measurements are estimates of the body’s
true core temp—central
• RECTAL—gold standard
• Esophageal—accurate but impractical
• Tactile and axillary—inaccurate, varies
considerably with environmental temperature
• Tympanic—inaccurate in age <3 years

9. 9
Categories
• Fever of short Duration
accompanied by localizing signs and symptoms, in
which a diagnosis can be established by clinical
history and physical examination
• Fever without localizing signs (without a Source or
Focus)
frequently in a child younger than 3 years old, in which
a history and PE fail to establish a cause, although a
diagnosis of occult bacteremia may be suggested by
laboratory studies
• Fever with unknown origin (FUO)
which defines fever for more than 14 days without an
identified etiology despite history, physical
examination, and routine laboratory tests or after 1
week of hospitalization and evaluation

10. 10
Fever of short Duration
• Initial complaints of infection may be
nonspecific, especially in infants who present
with fever, lethargy, irritability, excessive
sleeping, or poor feeding. Certain individual
physical findings, such as unique rashes, may be
diagnostic .
• Because of the varied presentations of infectious
diseases, it is important to investigate
thoroughly every objective finding from the
history and physical examination

11. 11
URTI Rhinorrhea, sore throat,
cough, drooling, stridor,
sinus pain, tooth pain,
hoarse voice
Nasal congestion,
pharyngeal erythema,
enlarged tonsils with
exudate, swollen red
epiglottis, regional
lymphadenopathy
Ear Ear pain or drainage Red bulging tympanic
membrane, drainage from
ear canal
LRTI Cough, chest pain, dyspnea,
sputum production, cyanosis
Tachypnea,
crackles, wheezing, localized
diminished breath sounds,
intercostal retractions
Localizing Manifestations of Infection

12. 12
GIT Nausea, vomiting, diarrhea,
abdominal pain, anorexia
Hypoactive or hyperactive bowel
sounds, abdominal tenderness
(generalized or focal).
Liver Anorexia, vomiting, dark urine,
light stools
Jaundice, hepatomegaly, hepatic
tenderness, bleeding diatheses, coma
Genitourinary tract Dysuria, frequency, urgency,
flank or suprapubic pain, vaginal
discharge
Costovertebral angle or suprapubic
tenderness, cervical motion and
adnexal tenderness
CNS Lethargy, irritability, headache,
neck stiffness, seizures
Nuchal rigidity, Kernig sign,
Brudzinski sign, bulging fontanel,
altered mental status, focal
neurologic deficits, coma
Cardiovascular Dyspnea, palpitations, fatigue,
exercise intolerance, chest pain
Tachycardia, hypotension,
cardiomegaly, hepatomegaly,
splenomegaly, crackles, petechiae,
Osler nodes, new or change in
murmur, distended neck veins,
pericardial friction rub, muffled
heart sounds
Skeletal Limp, bone pain, limited
function (pseudoparalysis)
Local swelling, erythema, warmth,
limited range of motion, point bone
tenderness, joint line tenderness

13. 13
The acute phase response
• nonspecific inflammatory response to infection,
trauma, autoimmune disease, and malignancies.
• such as erythrocyte sedimentation rate (ESR) and
C-reactive protein (CRP), are commonly elevated
during an infection, but are not specific for
infection and do not identify any specific
infection.
• These tests are often useful to show response to
therapy (e.g., osteomyelitis).

14. 14
complete blood count CBC
• obtained to identify evidence of bone marrow response to
infection.
• The initial response to infection, especially in children, is
usually a leukocytosis, with a neutrophilic response to
bacterial and viral infections.
• With most viral infections, the initial neutrophilic response
is transient and is followed quickly by the characteristic
mononuclear response.
• In general, bacterial infections are associated with greater
neutrophilia than are viral infections.

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• A shift to the left is an increase in the
numbers of circulating immature cells of the
neutrophil series (band forms, myelocytes) .
• A shift to the left indicates the rapid release of
cells from the bone marrow and characteristically is
seen in the early stages of infection and with
bacterial infections.
• Transient lymphopenia at the beginning of illness
and lasting 24 to 48 hours has been described with
many viral infections.

16. 16
• Atypical lymphocytes are mature T
lymphocytes that classically are seen with
infectious mononucleosis caused by Epstein-
Barr virus (EBV).
• Other infections associated with atypical
lymphocytosis include cytomegalovirus
(CMV) infection, toxoplasmosis, viral
hepatitis, rubella, roseola, mumps, and some
drug reactions.

17. 17
Other common screening tests include
• Urinalysis for (UTIs),
• Transaminases for liver function, and
• Lumbar puncture for evaluation of the CSF if
there is concern for meningitis or encephalitis .
• A grouping of various tests may help distinguish
viral versus bacterial infection, but definitive
diagnosis requires culture or PCR.

18. 18
Differentiating Viral from Bacterial Infections
Variable Viral Bacterial
Leukocytosis Uncommon Common
Shift to left (↑ bands) Uncommon Common
Neutropenia Possible Suggests overwhelming infection
↑ ESR Unusual Common
↑ CRP Unusual Common
IL-1 Uncommon Common
Meningitis (pleocytosis) Lymphocytic Neutrophilic

19. 19
Cultures are the mainstay of diagnosis.
• Blood cultures are sensitive and specific for bacteremia that may
be primary or secondary to a focus (osteomyelitis, GE, UTI,
endocarditis).
• Urine cultures confirm UTI, which may be occult in young
infants.
• CSF cultures should be obtained with any lumbar puncture.
• Other cultures are determined by the presence of fluid collections
or masses that are suspected to be infectious.
• Serologic tests, using enzyme-linked immunosorbent assay
(ELISA) showing an IgM response, high IgG, or seroconversion
between acute and convalescent sera can be used for diagnosis.
• Molecular detection methods, such as PCR for DNA or RNA,
offer the specificity of culture, high sensitivity, and rapid results.

20. 20
DIAGNOSTIC IMAGING
• Plain x-rays are useful for the middle and lower respiratory tract.
• Ultrasonography is a noninvasive, nonirradiating technique,
useful to identify soft tissue abscesses with lymphadenitis and
to diagnose suppurative arthritis of the hip.
• A voiding cystourethrogram (VCUG) is used to
evaluate for ureteral reflux, which is a predisposing factor for
upper UTIs.
• Radionuclide scans, such as technetium-99m for
osteomyelitis and dimercaptosuccinic acid (DMSA) for acute
pyelonephritis or chronic renal scarring, are often informative.

21. 21
• CT (with contrast enhancement) and MRI (with
gadolinium enhancement) allow characterization of
lesions and precise anatomic localization and are the
modalities of choice for the brain.
• CT shows greater bone detail
• MRI shows greater tissue detail. MRI is especially useful
for diagnosis of osteomyelitis, myositis, and necrotizing
fasciitis.
• High-resolution CT is useful for complicated chest
infections.
• Contrast studies (upper gastrointestinal series, barium
enema) are used to identify mucosal lesions of the
gastrointestinal tract.

22. 22
INITIAL DIAGNOSTIC
EVALUATION
• requires accurately recognizing the site of the infection ,
• recognizing all of the manifestations that are present,
• knowing all of the risk factors,
• recognizing exposure to potential infectious agents, and
• knowing the most likely organisms causing each infection .
• Obtaining a thorough history identifies most of these risk factors.

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• Season of year
• Age , Weight , Place of residence
• General health
• Change Fever-presence, duration, and pattern
• Previous similar symptoms
• Previous infections and other illnesses
• Previous surgeries Preceding trauma
• Presence of outbreaks or epidemics in the community
• Similar illness in close contacts
• Exposures to infected individuals
• Exposures to farm or feral animals ,Exposures to ticks and mosquitoes.
• Travel history
• Daycare or school attendance
• Sources of water
• Food and ingestion history, especially of undercooked meat or unpasteurized dairy
products
• Home sanitary facilities and hygiene
• Presence of foreign bodies (e.g., indwelling catheters, shunt, grafts)
• Immunization history
• Current medications
Risk factors

24. 24
Fever without a source (FWS)
• 5 to 20% of febrile children have no localizing
signs on PE and nothing in the history to explain
the fever. By definition, less than 7 days.
• FWS (like fever) is most common in children
younger than age 5, with a peak prevalence
between 6 and 24 months of age.
• Those <6 months retain protective maternal antibodies
against common organisms, while those 18-24 months
old are more immune competent, and are at a lower risk
of developing bacteremia

25. 25
Diagnostic Assessment in
Children
1) Age is important as etiologic pathogens,
2) clinical exam
3) immune system capacity changes as the newborn
ages.
• Most break them into the
1. Neonatal
2. 1-3 months
3. 3 to 36 months.

26. 26
Neonatal
• PE is felt to be unreliable in detecting many serious bacterial infections.
• Meningitis should always be considered—
up to 10% appear well,
15% have a bulging fontanelle, and
10-15% have nuchal rigidity.
So, a high index of suspicion is important!!! ~20% will not have
fever initially.
• Hyperthermia or hypothermia
• Lethargy or irritability or Seizures
• Poor feeding or vomiting
• Apnea, Dyspnea
• Jaundice
• Hypotension
• Diarrhea or abdominal distension
• Bulging fontanelle

27. 27
Neonates
• The majority of febrile neonates presenting to the
ED have a nonspecific viral illness
• 12% have serious bacterial infections (SBI)
• Infected by more virulent bacteria.
• The most common bacterial infections are UTI
and occult bacteremia

28. 28
Neonatal
Early Onset<7 Days
Group B Strep
E. Coli
Listeria Monocytogenes
Enterococcus
Strep viridans
Strep Pneumoniae
Hemophilus influenza nt
Herpes simplex
Later Onset>7 Days
Group B Strep
Listeria Monocytogenes
Strep Pneumoniae
Neisseria meningitidis
Herpes simplex

29. 29
Neonatal
• Risk Factors
• Preterm
• Membrane rupture: prolonged>12 hours
• Chorioamnionitis or maternal peripartum fever
• UTI
• Multiple pregnancy
• Hypoxia or Apgar score <6
• Poverty or age <20
• 1/3-1/2 neonatal sepsis will have no risk factors!

30. 30
Neonatal
• Screening tests:
WBC<5000 or >20,000,
PMN <4000,
Plt<100,000,
CRP>1,
LFTs elevated(suggest HSV)
• So, if <28 days of age and rectal temp> 38ºC
• Admit
• Blood Culture
• Urine Culture —cath specimen
• Lumbar Puncture
• Cell count, protein, glucose, culture, PCR
• Parenteral Antibiotics
• Ampicillin + Gentamicin (Cefotaxime), consider Acyclovir (primary
maternal infxn, esp if delivered vaginally, PROM, fetal scalp electrodes,
skin eye or mouth lesions, seizures, CSF pleocytosis)

31. 31
Infants 1 to 3 months
• Causes
• HSV (17% are 15 days to 6 weeks of age)
• Bacterial sepsis/meningitis
• Group B Strep, S. Pneumoniae, H. influenza, N. meningitidis.
• Bone and joint infections
• UTI
• Bacterial enteritis (esp Salmonella)
• Pneumonia
• Enterovirus sepsis/meningitis(July-October)
• The risk of bacteremia/meningitis is 3.3%, pneumonia,
bone/joint infections and bacterial enteritis is 13.7%
• 30-50% of those who are ultimately diagnosed with bacterial
meningitis have been seen by a physician within the prior
week(usually 1-2 days before) and were diagnosed as having a
trivial illness and discharged on oral antibiotics.

32. 32
Infants 1 to 3 months
Infants who are toxic and febrile have a much higher
risk of serious bacterial infection. They should be
admitted, have a full sepsis workup, and given
antibiotics/antiviralsAmpicillin and Cefotaxime.
Infants who are nontoxic and febrile who meet all
Rochester criteria can ‘safely’ be treated as an
outpatient. Generally, 1-3% of children
meeting these criteria will develop a serious
bacterial infection, 0.7% bacteremia, 0.14%
meningitis.

33. 33
Infants 1 to 3 months
• Rochester Criteria/Low Risk Criteria
• Nontoxic—most critical and difficult
• Previously healthy, not low birth weight
• No focal bacterial infection on PE except Otitis
Media
• WBC 5,000-15,000/mm3
(normal)
• Bands<1500/mm3
(normal)
• Normal urinalysis, including gram stain
• If diarrhea, must be non-bloody and WBC<5/hpf.
• If respiratory symptoms present, normal CXR

34. 34
Infants 1 to 3 months
• If all of the criteria are met, then there are 2 options
for outpatient management:
• 1) Blood, Urine Cultures, LP, Ceftriaxone 50mg/kg IM
(to 1g), and return for reevaluation within 24 hours.
• 2) Blood, Urine Cultures and careful observation.
• Parents should have mature judgment, can return
within 30 minutes and have a thermometer and a
phone.
• IF NO LP IS DONE, DO NOT GIVE
CEFTRIAXONE

35. 35
Infants 1 to 3 months
• Follow-up of low risk infants
• If all cultures negative: afebrile, well
appearingCareful observation
• Blood cultures negative: well appearing,
febrileCareful observation, may consider second
dose of Ceftriaxone
• Blood culture positiveadmit for sepsis workup and
parenteral antibiotics pending results
• Urine culture positive: if persistent feveradmit for
sepsis workup, parenteral antibiotics pending results.
If afebrile and welloutpatient antibiotics

36. 36
Infants 3 to 36 months
• Infant sepsis syndrome:
• Age 3-36 months
• Fever>39ºC
• ANC>10,000
• If a child meets all 3 criteria, he has a 3% risk for
pneumococcemia. If untreated, 3% will progress to
meningitis.
• Other causes: HHV6(15%), UTI(girls 3%, boys 0.6%),
menigococcemia(0.1%), Salmonella(0.2%), H. influenza
(0.05%), Enterovirus (JulyOctober).

37. 37
Infants 3 to 36 months
• UA with micro, CBC with differential, Blood
Cultures
• LP if meningeal signs, petechiae, purpura or toxic.
• Antimicrobials:
• OM or pneumonia: cover for pneumococcus, non-typable
H. flu and Moraxella: amoxicillin+augmentin, ceftriaxone
• URI or no focus: cover for pneumococcus and
menigococcus: amoxicillin(80-100mg/dg/day),
ceftriaxone
• Pneumococcemia: promptly reassess, if well, should at
least treat with 1 dose ceftriaxone.

38. 38
Occult Bacteremia
5% of children with FWS have OCCULT
BACTEREMIA
• The presence of a positive blood culture in kids
who look well enough to be treated as
outpatients .

39. 39
Occult Bacteremia
• Streptococcus pneumonia is responsible for 2/3 to
¾ of all cases.
• Peak prevalence between 6 and 24 months
• Association with high fever(39.4ºC)
• High WBC count(>15,000)
• Absence of evident focal soft tissue infection.
• Neisseria meningitidis, Haemophilus influenzae
type b, and salmonellae account for most of the
remaining cases.

40. 40
Risk of Occult Bacteremia
Blood culture is the gold standardstill has a high
number of false positives, take 24-48hrs, and most
cases of occult pneumococcal bacteremia clear
without treatment.
Low Risk
Age >3yr
Temp <39.4ºC
WBC >5000 and
<15,000
High Risk
<2yr
>40ºC
<5000 or >15,000
Hx of contact with H. Flu
or N. meningitidis

41. 41
Occult Bacteremia
• Empiric antibiotics should be targeted against S.
pneumoniae, N. meningitidis, and H. influenza
• Amoxicillin
• Augmentin, Bactrim, 2nd
or 3rd
gen Cephalosporins
• Single dose Ceftriaxone 50-75mg/kg
• Follow up is essential !

42. 42
Definition of FUO?
•Optimal definition of FUO:
Fever greater than 38.3C for two
weeks or longer
Fever of Unknown Origin FUO

43. 43
Etiology of FUO
• “A fever of unknown origin is more likely to
be the unusual presentation of a common
disorder than the common presentation of
a rare disorder”

44. 44
Etiology of FUO
• Infections 30-40%
• Autoimmune 7-10%
• Malignancy 2-5%
• Other (incl.. factitious fever, drug fever) 2%
• Never determined: In up to 50%

45. 45
Infectious Causes of FUO in children
• n= 454 children from several studies
• Infectious mononucleosis: (EBV or CMV)
• Infection of the upper or lower respiratory tract
• Urinary tract infection
• Osteomyelitis
• Cat scratch disease
• CNS viral or bacterial infection
• Tuberculosis

46. 46
Infectious Causes of FUO in children:
less common pathogens
• HIV,
• brucellosis
• Q fever
• dengue fever
• malaria
• leptospirosis
• toxocara canis and toxocara cati
• histoplasmosis
• coccidioidomycosis
• blastomycosis
• psittacosis
• Lyme disease
• salmonellosis (typhoid fever)

47. 47
Other considerations for infectious
causes of FUO
• Intraabominal abscess
• Liver abscess
• Occult dental infection
• Endocarditis

48. 48
Non-infectious etiologies of FUO
• Collagen vascular and immune mediated
disease:
• JRA
• SLE
• ARF
• AKD (atypical Kawasaki Disease)

49. 49
Noninfectious Etiologies of FUO
• Inflammatory bowel disease
• Malignancy
• Drug Fever
• Munchausen syndrome by proxy
• Dysautonomia
• Central thermoregulatory disorder
• Immune disorder

50. 50
Periodic Fever Syndromes
• Idiopathic
• Cyclic neutropenia
• Hyper IgD Syndrome
• Familial Mediterranean Fever

51. 51
Approach to the evaluation of the child with
an FUO
• “The tempo of the evaluation should match
the clinical appearance of the child!”
• Document the existence of fever
• Note the general well being of the child
• School absenteeism
• Changes in social behavior

52. 52
Diagnosis: History
• Leave no stone unturned.
• May need to repeat the history
• Remember to include: PH, Allergies, Medics,
FH, Social History, Immunizations, Travel and
Animal exposure

53. 53
Animals and bugs
• Rabbits, squirrels: tularemia
• Cats: cat scratch disease (Bartonella henselae),
tularemia, rabies, toxoplasmosis
• Birds: Psitticosis
• Sheep: Q fever
• Goats: Brucellosis
• Ticks: Lyme disease, relapsing fever, ehrlichiosis.
• Mosquitoes: Malaria, dengue fever, yellow fever,
arboviral encephalitis
• Fleas: Cat scratch disease (also need the cat).
• Dogs, skunks, raccoons, bats: Rabies

54. 54
Travel History
• Foreign: Consider calling the CDC to check
for illnesses endemic to area visited. Think
about malaria, dengue, typhoid, hepatitis A
and tuberculosis, parasites, HIV

55. 55
Family and social history
• Drug abuse
• ?HIV
• Previous history of transfusions
• Ill family members (TB)
• Frequent childhood deaths (immune deficiency)

56. 56
Clues on physical exam
• Pattern of fever
Intermittent fevers (hectic or spiking fever) suggest pyogenic infection
Remittent fevers, fluctuating peaks and a baseline that does not return
to normal. viral infections, bacterial infections, especially
endocarditis.
Persistent fevers with little or no fluctuation are sustained fevers;
typhoid fever and typhus
Relapsing fevers with periods during which patients are afebrile for one
or more days between febrile episodes malaria, infection with the
Borrelia and lymphomas.
Recurrent episodes of fever over periods of more than one year's
duration suggest metabolic defects, (CNS) dysregulation of
temperature control, periodic disorders (such as cyclic neutropenia,
hyper IgD syndrome, and immunodeficiency states.
• Sweating: Hyperthyroidism
• No sweating: ectodermal dysplasia
• Weight loss, growth curves
• ArthralgiaArthritis, myalgia: collagen disease, neoplasm,

57. 57
Clues on physical exam
• Heart murmur or previous history of heart
disease: sub-acute bacterial endocarditis
• GI: IBD, celiac disease, ruptured appendix,
liver abscess, perinephric abscess
• Large spleen: malignancy, endocarditis,
infectious mononucleosis
• Do a good neurologic exam

58. 58
Clues on physical exam
• Remember to do a rectal and GU exam
• Skin: eczema/seborrhea (histiocytosis,
immune deficiency)
• Palpate bones and extremities

59. 59
Diagnostic evaluation
• *Adapted from Steele et. al
• Phase I (outpatient)
• Based on findings from the history and physical consider the
following tests:
• CBC
• ESR
• Urinalysis and culture
• Serum chemistries to include LFT’s

60. 60
Diagnostic evaluation
• Phase 1 Outpatient: continued
• CXR, abdominal ultrasound
• PPD, thick and thin smear for malaria
• Monospot/EBV serology
• Cat scratch serology (B. henselae and quintana)
• HIV test (ELISA ab unless pt. <12 mos, then
HIV PCR)
• Blood culture, Stool, occult and culture

61. 61
Diagnostic evaluation
• Phase 2
• Hospitalize for observation/Consider
referral to ID, Rheumatology or Heme Onc
• LP
• Sinus CT
• Repeat blood culture
• Bone scan
• Bone marrow
• Echocardiogram

62. 62
Diagnostic evaluation
• Serologic tests (generally helpful only if acute
and convalescent titers are obtained or IgM is
positive)
• Gallium/Indium scans: Several studies have
shown these tests are only helpful if probable
focus of infection has been identified!

63. 63
Therapy
• Try NOT to start empiric oral or
parenteral antibiotic therapy if you don’t
know what you are treating.
• Empiric antibiotics only if patient appears ill
(and remember to get cultures first)
• NSAID
• Never ever ever treat empirically with
steroids

64. 64
Outcome
• Depends on underlying diagnosis
• Most patients in whom the source of fever
is never determined after a thorough and
comprehensive evaluation have resolution
of symptoms and do well

65. 65
Antipyretics
• Acetaminophen, Ibuprofen
• Efficacy and safety of alternating
acetaminophen and ibuprofen not studied

66. 66
Conclusion
• A careful and complete history, frequent re-
examination of the child and patience will
usually reveal the answer.

67. 67
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