an approach to fever without a source in infants and children authors: dr. april kam md, dtmh,...
TRANSCRIPT
An Approach to Fever without a Source in Infants and Children
Authors:
Dr. April Kam MD, DTMH, MScPH, FRCPC
Parnian Arjmand MSc, MD Candidate
Dr. David Goldfarb MD, FRCPC
Date Created: December 2012
Learning Objectives
Be able to define Fever Without a Source (FWS)
Develop an approach to categorizing and managing a child presenting with fever
Learn about some of the key red flags and special circumstances for children presenting with fever
Caveats…
Need to be aware of local epidemiology Prevalence of infections can vary dramatically based
on geography, season, context of epidemic
Fever Differential Diagnosis can be quite broad– we will only cover most commonly seen entities
Broaden your differential, particularly in immunocompromised children (e.g. HIV, severely malnourished, etc.)
Caveats…(cont’d)
In many countries the epidemiology is changing dramatically due to newly introduced vaccines (e.g. Hib, PCV) and the spread of HIV
Can often see co-infections e.g. Among < 5 yr olds in Nigeria with confirmed
malaria, 9% also had UTI (Okunola PO et al., 2012)
Caveats… (cont’d)
Very little published data on the management of fever without localizing signs in children in the developing world
Drug resistance rates climbing dramatically in the developing world…
Target Audience
Health care providers working at first level referral centre – primary care hospital
Basic laboratory facilities (e.g. microscopy) and medications available
Need to adapt to your facility based on epidemiology, testing, and antimicrobials available – know the local guidelines!
Main reference
Integrated Management of Childhood Illnesses – Management of a Child with Serious Infection or Severe Malnutrition
https://apps.who.int/chd/publications/referral_care/contents.htm
Definitions
Fever without a Source (FWS) or Fever without Localizing Signs (FWLS) or Fever without a Focus (FWF):
Rectal temperature > 38°C (> 101ºF) in an infant or child w/ a physical exam that does not suggest a focus of infection
Fever
An intrinsic adaptive response that activates the immune system
Is controlled by the hypothalamus Shortens the length of disease
Etiologies
Infection Infection Infection Other causes much less likely
Inflammation – e.g. Kawasaki disease CNS disorder – e.g. Hypothalamic dysfunction Metabolic Iatrogenic: drugs, immunizations
4 Major Categories for child presenting with fever
Fever due to infection without localized signs – i.e. FWLS (no rash) in > 2 mo
Fever due to infection with localized signs (no rash) in > 2 mo
Fever with rash in > 2 mo Special Situations/Red Flags
Young infant (7 days - 2 months) – high risk serious bacterial infection
HIV infection Severe Malnutrition
Differential Dx of FWLS (no rash)Diagnosis of fever In favour
Malaria (only in children exposed to malaria transmission)
• Blood film or rapid test positive• Severe anemia• Enlarged spleen• Jaundice
Septicemia • Seriously and obviously ill with no apparent cause• Purpura, petechiae• Shock or hypothermia in young infant
Typhoid • Seriously and obviously ill with no apparent cause• Abdominal tenderness• Shock• Confusion
Urinary tract infection • Incontinence in previously continent child• Vomiting with no diarrhea• Crying on passing urine or increased frequency• White blood cells, bacteria or nitrites on micro/UA
Fever associated with HIV infection
• Signs of HIV infection (see red flags)
Differential Dx of Fever with localizing signs (no rash)
Diagnosis of fever In favour
Meningitis • LP positive• Stiff neck• Bulging fontanelle• Meningococcal rash (petechial or purpuric)
Otitis media • Red immobile ear-drum on otoscopy• Pus draining from ear• Ear pain
Mastoiditis • Tender swelling above or behind ear
Osteomyelitis • Local tenderness• Refusal to move the affected limb• Refusal to bear weight on leg
Skin and soft tissue infection
• Cellulitis• Boils• Skin pustules• Pyomyositis (purulent infection of muscle)
Differential Dx of Fever with localizing signs (no rash) – cont’d
Diagnosis of fever In favour
Pneumonia • Cough with fast breathing• Lower chest wall indrawing• Fever• Coarse crackles• Nasal flaring• Grunting
Viral upper respiratory tract infection
• Symptoms of cough/cold (e.g. rhinorrhea)• No systemic upset
Throat abscess • Sore throat in older child• Difficulty in swallowing/drooling of saliva• Tender cervical nodes
Sinusitis • Facial tenderness on percussion over affected sinus• Foul nasal discharge
Differential Dx of Fever with rashDiagnosis of fever In favour
Measles • Typical rash• Cough, runny nose, red eyes• Mouth ulcers• Corneal clouding• Recent exposure to a measles case• No documented measles immunization
Viral infection • Mild systemic upset• Transient non-specific rash
Meningococcal infection • Petechial or purpuric rash• Bruising• Shock• Stiff neck (if meningitis)
Relapsing fever (borreliosis)
• Petechial rash/skin haemorrhages• Jaundice• Tender enlarged liver and spleen• History of relapsing fever• Positive blood smear for Borrelia
Typhus • Epidemic of typhus in region• Characteristic macular rash
Dengue Hemorrhagic Fever (or other HFs)
• Bleeding from nose or gums, or in vomitus• Bleeding in stools or black stools• Skin petechiae• Enlarged liver and spleen• Shock• Abdominal tenderness
Special Situations/Red Flags
Young infant – 7 days to 2 months
HIV infected child
Severely malnourished child
Young infant 7 days – 2 months
Presume Serious Bacterial Infection e.g. Pneumonia, sepsis, meningitis
Show less specific signs Can present with Fever or Hypothermia Irregular breathing, jaundice, apnea, grunting, seizure,
vomiting, abdominal distension, lethargy, anorexia
HIV infected or potentially infected
HIV infected children have higher risk of sepsis and opportunistic infections
Signs common to HIV infected infants: Recurrent infections, oral thrush, chronic parotitis,
generalized lymphadenopathy, hepatosplenomegaly, persistent/ recurrent fever lasting >7 days, neurological dysfunction, Herpes Zoster, HIV dermatitis
More specific signs: pneumocystic pneumonia, esophageal candidiasis, lymphoid interstitial pneumonia, shingles or Kapsosi sarcoma
Signs common to both HIV infected and non-infected infants: chronic otitis media, persistent diarrhea, failure to thrive
Severe Malnutrition
Definition - edema in both feet or severe wasting and weight for height < -3 SD or <70%
Assume that all severely malnourished children have an infection (regardless of presence of fever) and treat with antibiotics
On exam look for: dehydration, pallor, signs of HIV infection/ local infection, fever, ulcers, skin changes of kwashiorkor
History Duration of fever Residence in or recent travel to an area with Plasmodium
falciparum (malaria) transmission Skin rash Stiff neck or neck pain Headache Pain on passing urine (generally child ≥ 3yr) Ear pain – e.g. pulling on pinna Immunizations
History (cont’d) What was the temperature and how was it measured? Level of activity prior and after onset of fever Infection(s) during pregnancy or at birth Ill contacts or recent travel history Oral intake Presence of lethargy/ irritability Presence of cough/ vomiting Urination frequency/ abdominal pain/ back pain/ new onset of
incontinence (e.g. UTI) Protection of the affected area in deep soft tissue/ bone infection Underlying medical conditions (e.g. sickle cell disease, urinary tract
reflux, etc.)
History (cont’d) - Immunizations It is particularly important to know if Hib, pneumococcal, meningococcal
and/or yellow fever vaccines have been given and are up to date
Nearly all low income countries have now rolled out Hib vaccine > 18 countries in developing world have also recently introduced
PCV 6 countries in sub-Saharan “meningitis belt” have just introduced
new meningococcal A conjugate vaccine Rapid increase in number of children vaccinated against yellow
fever with assistance GAVI
Vaccination with the above conjugate vaccines (i.e. Hib, PCV) dramatically reduces the risk of occult bacterial infection in children presenting with fever without localizing signs
Physical Examination Always fully undress child General appearance (alert, playful, irritable, consolable,
lethargic) Oxygen saturations (if available) Stiff neck Hemorrhagic skin rash - purpura, petechiae Skin infections - cellulitis or skin pustules Discharge from ear/red immobile ear-drum on otoscopy Severe palmar/conjunctival pallor Refusal to move joint or limb Local tenderness Fast breathing
Physical Examination Toxic-appearing:
Lethargic: decreased level of consciousness/ poor eye contact, failure to interact with environment or parents
Poor perfusion and cyanosis Hypo/ hyperventilation Purpura may be present Woods, CR.
Epiglottitis (supraglottitis): Clinical features and diagnosis. In: UpToDate, Basow, DS (Ed), UpToDate, Waltham, MA, 2012.
Physical Examination
Watch for signs of raised intracranial pressure: Bulging fontanelle Poor feeding, Vomiting Headache, Irritability Papilledema Lethargy, Seizures Cushing’s triad: hypertension, widened pulse
pressure, bradycardia
Fever 2 months – 3 years
The first step is to determine if the child is toxic looking i.e. septic If the patient is septic, do septic work up and
start antibiotics, fluids, and provide oxygen
Fever 2 months – 3 years
In the non-septic child, the second step is to determine if the fever is due to an infection with or without localized signs by doing a detailed history and physical If a focus is found, treat accordingly If no focus is found, investigate as FWLS or
Fever without a source
Fever 2 months – 3 years
Example of an institutional algorithm for FWLS in the 2 m – 3 year age group developed for Botswana referral hospital (where there is very low/no malaria, no typhoid, no dengue) is provided on the next page
Child Appears Toxic• Lethargic (not interacting with caregivers/environment)•Poorly perfused (cap refill > 2sec)•Hypoventilating or tachypneic for age
No
Algorithm: Fever without a Source – Ages 2 months to 3 years
Definition: Child between 2 months and 3 years with an axillary temperature > 37.5 and no obvious source of infection after a thorough History and Physical
Yes
T > 38.5 axillaryNoYes
Sepsis evaluation•Blood Culture•Urinalysis and Culture•CBC•LP if indicated by symptoms•Consider malaria smear if indicatedAdmit to WardStart empiric antibiotics- Cefotaxime 50mg/kg/dose 6 hourly
•No diagnostic test•Paracetemol 15mg/kg/dose•Discharge home•Return if fever > 48 hrs or seems more sick•NO Antibiotics
Tests: Blood Cx or FBC and then Blood Cultures only if WBC > 15,000UA and Cx: if Male < 6 mo, Female < 2 yr or T > 40CXR: if dyspnea, cough/ralesLP: if < 15 mo, or associated with seizure and does not meet criteria for simple febrile seizure
Child is HIV positive, CD4 <25% or unknown or child is HIV Exposed and HIV status unknown
YesNo
Treatment:- If any diagnostic tests are suggestive of a source for infection treat according to protocol for that diagnosis . However, if no tests are indicated or all test are normal AND If FBC or WBC > 15,000 THEN -> Amox/Clav for 48 hours If FBC or WBC < 15,000 then do not give antibiotics ALL children regardless of whether they are given abx NEED: F/U in 48 hours if still febrile or at any time if they appear more sick & Paracetemol 15 mg/kg/dose
*Normal Rates
Age Respiratory Heart
2-12 months <50/min <160/min
1-2 years <40/min <120/min
2-5 years <40/min <110/min
6-8 years <30/min <110/min
Management – Presumed Septicemia
Treatment Give benzylpenicillin IV (50 000 units/kg every 6 hrs)
or ampicillin 50 mg/kg IM every 6 hrs) plus chloramphenicol (25 mg/kg every 8 hrs) for 7 days
If significant drug resistance to these antibiotics among Gram-negative bacteria, follow the local guidelines for management of septicaemia may be a third-generation cephalosporin such as ceftriaxone (80 mg/kg IV, once daily over 30-60 minutes) for 7 days
Management – Presumed Septicemia (cont’d)
Supportive care If a high fever of ≥ 39°C (≥ 102.2°F) is causing
the child distress or discomfort, give paracetamol (15mg/kg/dose every 4 hours, maximum 5 doses/day )
Fluid intake and nutritional management
Manage complications including seizures, hypoglycemia, electrolyte abnormalities
Investigations for FWLS – Depending on availability
Blood smear or rapid diagnostic test (RDT) for malaria (if endemic)
LP if signs suggest meningitis (with no signs of raised intracranial pressure, in stable patient)
Blood culture in suspected sepsis Full Blood Count Urinalysis/Microscopy CXR – if pneumonia is suspected
Management 7 day to 2 month old
Investigations: Check glucose Do Cultures – Urine and Blood Do an LP CXR if available
Management: Oxygen, Fluids, Antibiotics
Management 7 day to 2 month old
Ampicillin (50 mg/kg IM/IV every 6 hrs for 2 days) then oral amoxicillin (15 mg/kg every 8 hrs for 5 days) OR oral ampicillin (50mg/kg PO every 6 hrs on an empty stomach for 5 days)
plus IM gentamicin (7.5 mg/kg once daily) for a total of 7 days of therapy
You may continue IV Ampicillin beyond 2 days if child continues to appear unwell
Management 7 day to 2 month old (cont’d)
If S. aureus is known to be an important cause of neonatal sepsis locally, or signs suggestive of severe staphylococcal infection (e.g. skin pustules), give IM cloxacillin (50 mg/kg every 6-8 hrs depending on age) plus IM gentamicin (7.5 mg/kg once daily)
Management 7 day to 2 month old - Suspected or Confirmed Meningitis
Give IM ampicillin (50 mg/kg every 6-8 hrs depending on age) plus IM gentamicin (7.5 mg/kg once daily). An alternative regimen is IM ampicillin plus IM chloramphenicol (25 mg/kg every 6 hours).
Chloramphenicol should not be used in premature infants and should be avoided in infants in the first week of life
Some centres use third generation cephalosporins
Investigations may include
Glucose (mandatory) Labs: Hb/ Htc if severe pallor Electrolytes (generally hypokalemic) Blood culture TB investigations HIV testing, etc.
Management of child admitted with severe malnutrition
Multidimensional management in two phases of stabilization and rehabilitation [see chapter 7 in the WHO manual]
Management of child admitted with severe malnutrition
All severely malnourished children receive A broad-spectrum antibiotic
Ampicillin (50 mg/ kg IM/IV 6-hourly for 2 days) then oral amoxicillin (15 mg/ kg 8-hourly for 5 days) OR oral ampicillin (50 mg/kg IM/IV for 5 days) over a total of 7 days
Gentamicin (7.5 mg/kg IM/IV) once daily for 7 days
If child fails to improve within 48 hours: add chloramphenicol (25 mg/kg IM/IV 8-hourly) for 5 days
Local antibiotic regimen may be different due to different resistance rates
Management of child admitted with severe malnutrition
Measles vaccine if child > 6 mo (not immunized) or > 9 month
Delay vaccination if in shock
Diagnostic Criteria for Urinary Tract Infections
Clinical signs: Malodorous urine/ hematuria Abdominal tenderness/ suprapubic pain Vomiting, irritability, diarrhea Fever > 38 °C for over 24 hrs Dysuria, vaginitis/ vulvalitis
Labs: Urinalysis from suprapubic aspirate or transurethral catheter
Leukocyte esterase Nitrite WBC Culture
Treatment of Urinary Tract Infections
For Oral agents, be aware of local susceptibilities – treatment include: Amoxicillin/Clavulanate, First generation
cephalosporins, Quinolones
If <6months, or septic, require admission and IV Ampicillin & Gentamicin
Other Common Infections Malaria (see-
http://apps.who.int/medicinedocs/documents/s19105en/s19105en.pdf for details) Varies by severity, endemic species, and resistance patterns Antimalarial treatment:
IM/IV Artesunate first line for severe malaria due to P. falciparum in most regions (pre-referral rectal artesunate an option)
Measles Two doses of Vitamin A to all children; immediately on diagnosis
and within 24 hours
Other Common Infections Typhoid
Chloramphenicol (25 mg/ kg every 8 hours) for 14 days If systemic signs/ upset: benzylpenicillin (50 000 units/ kg every 6
hours) for 14 days in addition to chloramphenicol (dosed as above)
Ear infections Acute otitis media - Amoxicillin (50 mg/kg PO TID) X 7 days Chronic suppurative otitis media – wicking and topical antibiotic such as
chloramphenicol drops if available
Summary FWS: fever without a specific source in an acutely ill, temp (rectal)
> 38ºC (100.4ºF)
Infection is the most common etiology of FWS
There are four categories of infants presenting with fever: young infant with serious risk of bacterial infection, infectious fever without rash, fever due to infection with localized signs, and fever with rash
Management strategies vary depending on geographical area, access to resources, presentation, and infant age
Red flags to watch out for: severely malnourished infant, infant with signs of HIV and young infant (7 days to 2 months)
General References
MANAGEMENT OF THE CHILD WITH A SERIOUS INFECTION OR SEVERE MALNUTRITION Guidelines for care at the first-referral level in developing countries. WHO. 2000
IMCI UTI guidelines: Urinary Tract Infections in Infants and Children in Developing Countries in the Context of IMCI http://whqlibdoc.who.int/hq/2005/WHO_FCH_CAH_05.11.pdf
Credits
Dr. April Kam MD DTMH MScPH FRCPC
Assistant Professor, Pediatric Emergency Medicine
Department of Pediatrics, McMaster Children’s Hospital
Parnian Arjmand MSc MD Candidate
McMaster University
Dr. David Goldfarb MD FRCPC
Assistant Professor, Infectious Diseases
Department of Pediatrics, McMaster Children’s Hospital
Adjunct Senior Lecturer, University of Botswana