Meningitis

Epidemiology Overview

Asymptomatic Carriage

• Approximately 10% of the population carry Neisseria meningitidis asymptomatically in the nasal passages.

Invasive Meningococcal Disease (IMD)

• IMD commonly presents as either meningitis or septicaemia (sepsis).
• Septicaemia is associated with particularly severe disease and carries a higher mortality rate.

Age Distribution

• There is a bimodal distribution in age groups affected:
  • 0-4 years old
  • 15-25 years old

Pathogens in Infants Under 2 Months

• Key organisms to consider for bacterial meningitis in infants less than 2 months include:
  • Group B Streptococcus
  • Escherichia coli (E. coli) and other Gram-negative organisms
  • Listeria monocytogenes

Common Causative Organisms in Children Over 2 Months

• In children older than 2 months, the most common bacterial causes of meningitis are:
  • Streptococcus pneumoniae
  • Neisseria meningitidis
  • Haemophilus influenzae type B (Hib) in unimmunised children

Neisseria meningitidis

• There has been a significant decline in cases of Serogroup C meningococcal disease since the introduction of a vaccination programme in 2004.
• Serogroup B now represents 78% of bacterial isolates.
• Case fatality rate for meningococcal disease is approximately 11.6%.

Special Populations

• Consider other pathogens in:
  • Patients with anatomical abnormalities of the central nervous system (CNS)
  • Those with ventricular shunts
  • Immunosuppressed children
  • Individuals with a history of travel to areas with endemic pathogens

Encephalitis Etiology

• Viral Causes:
  • Enteroviruses
  • Herpes Simplex Virus (HSV)
  • Other herpes viruses, such as Epstein-Barr Virus (EBV), Cytomegalovirus (CMV), Human Herpesvirus 6 (HHV-6), and Varicella-Zoster Virus (VZV)
  • Arboviruses
• Less commonly, bacteria, fungi, or parasites may also cause encephalitis.

Long-Term Complications

• Approximately 33% of survivors of meningitis and encephalitis experience long-term complications, including:
  • Learning and academic difficulties
  • Hearing impairment (7%)
  • Neurological deficits (12.2%)
  • Behavioural (14.8%) and motor deficits (10.4%)

Vaccination Developments

• Vaccines targeting Serogroup B are currently in Phase 1 clinical trials.

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Risk Factors for Meningitis

Neonates

• Prematurity
• Low Birth Weight
• Delivery Complications
• Maternal Group B Streptococcal Colonization
• Maternal Infections (e.g., herpes simplex virus)

Older Children

• Low Family Income (linked to limited access to healthcare and crowded living conditions)
• Daycare Attendance (increased exposure to pathogens)
• Head Trauma
• Splenectomy
• Chronic Diseases (e.g., HIV, other immunocompromising conditions)
• Concurrent Infections

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Differentials for Headache and Fever

Intracranial Infections

• Meningitis
• Encephalitis
• Sinusitis

Systemic Infections/Other Organs

• Influenza
• Lower Respiratory Tract Infections (LRTI) & Sepsis
• Urinary Tract Infection (UTI) Sepsis
• Epstein-Barr Virus (EBV)
• Infective Endocarditis
• Exotic Infections from Travel
  • Dengue
  • Malaria
  • Typhoid Fever
• Regional Australian Infections
  • Q Fever
  • Barmah Forest Virus

Non-Infectious Causes

• Subarachnoid Haemorrhage
• Giant Cell Arteritis (in elderly adults)

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Assessment of Suspected Meningitis

History Taking

• Initial Symptoms may mimic common viral infections.
• Fever and other systemic signs should be carefully assessed.
• Immunisation History
• Recent Antibiotic Use

Symptoms in Infants:

• Minimal or Non-Specific Symptoms such as irritability, lethargy, or poor feeding
• Hypertonia or Hypotonia
• Vomiting and Diarrhoea
• Temperature Instability

Symptoms in Children:

• Any of the above symptoms and/or:
  • Headache
  • Photophobia
  • Nausea
  • Altered Conscious State
  • History of Recent Upper Respiratory Tract Infection (URTI)

Encephalitis Features

• Altered Mental State: Subtle changes can depend on the affected region of the brain.
  • Unusual Behaviour
  • Confusion
  • Personality Changes
  • Emotional Lability
  • Seizures

Predisposing Medical Conditions

• CNS Anatomical Abnormalities or Shunts
• Immunosuppression
• Immunodeficiency

Physical Examination

• General Appearance: Febrile, irritable, lethargic, poor feeding
• Fontanelle (in infants): Bulging (if open)
• Neck Stiffness: May be absent in young children and infants; not always a reliable sign.

Special Signs:

• Kernig Sign:
  • With the child supine, the examiner flexes one hip and knee to 90 degrees and attempts to extend the knee.
  • Positive sign: Pain along the spinal cord or resistance to knee extension.
• Brudzinski Sign:
  • With the child supine and legs extended, the examiner flexes the neck.
  • Positive sign: Reflex flexion of the hips and knees.

Rash:

• Petechial or Purpuric Rash: May be present anywhere on the body. An early rash can resemble viral exanthema but may progress rapidly.
  • The presence of purpura is a late sign suggestive of meningococcal sepsis but may be absent in the early stages of overwhelming sepsis.

Red flag features in Red

Meningitis	Encephalitis
History Fever Immunisation history Recent antibiotic exposure Infant:  = minimal or non-specific symptoms = irritability l= ethargy or drowsiness = poor feeding = hyper or hypotonia = vomiting and diarrhoea = temperature instability Child, any of the above and/or: = headache = photophobia = nausea = altered conscious state   Preceding URTI may be present Seizures Medical condition that may predispose child to meningitis (eg CNS anatomical abnormality or shunt, immunosuppression, immunodeficiency)	History Fever Features of altered mental state can be subtle and depend on the affected region of the brain: = unusual behaviour = confusion = personality change = emotional lability Seizures (common) Headache Nausea and vomiting Consider other causes of encephalopathy eg ADEM, toxins or metabolic
Examination Full fontanelle High-pitched cry  Fever or hypothermia Apnoea Neck stiffness (may be absent in infants) Focal neurological signs  Purpuric rash is a late sign suggestive of meningococcal sepsis Pain and involuntary effort to reduce meningeal “stretch” eg Kernig and Brudzinski signs	Examination Focal neurological signs

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Investigations

• Febrile unwell infant should have – FBC, BSL, lactate, CRP, blood culture, urine MCS
• Depending on age/symptoms – LP or CXR
• CSF – high WCC, possibly RBCs, glucose < 60% of serum, incresed protein
• MCS of CSF
• Lumbar puncture
  • Contraindicated if there’s
    • focal neurological signs 
    • new or prolonged seizures 
    • rapidly decreasing GCS (which could be argued in the this patient) 
    • papilloedema 
    • on anticoagulants 
    • known to be immune deficient 
• CT brain
  • Do BEFORE LP if there’s signs of raised intracranial pressure (ICP)
  • Also CT Head first if:
    • (1) new onset seizures
    • (2) immunocompromised
    • (3) GCS < 10
    • (4) focal neurological signs in keeping with a space occupying lesion.
    • (5) encephalitis
    • (6) focal neurological signs
    • (6) diagnostic uncertainty (eg to look for a mass)
  • Is not routine in meningitis but is used to look for complications eg abscess, thrombosis
  • Normal head CT does not exclude raised ICP and should not influence the decision to perform an LP
  • MRI will provide more detailed information to guide diagnosis, but may require general anaesthetic

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Management

1. Antimicrobials

Antibiotics must not be delayed for more than 30 minutes after the decision to treat is made
Antimicrobial recommendations may vary according to local antimicrobial susceptibility patterns; please refer to local guidelines

Age group	Common organisms	Empiric antibiotic	Dexamethasone
Meningitis
0–2 months	Group B streptococci (GBS), Escherichia coli, Listeria monocytogenes (rare)	Benzylpenicillin 60 mg/kg IV 12H (week 1 of life) 6–8H (week 2–4 of life) 4H (>week 4 of life) and  Cefotaxime 50 mg/kg (max 2 g) IV 12H (week 1 of life) 6–8H (week 2–4 of life) 6H (>week 4 of life)	Not advised
≥2 months	N meningitidis, HiB, S pneumoniae	Ceftriaxone 50 mg/kg (max 2 g) IV BD or  Cefotaxime 50 mg/kg (max 2 g) IV QID Add Vancomycin if Gram-positive cocci on Gram stain	0.15 mg/kg (max 10 mg) IV 6H for 4 days
Encephalitis
	Mycoplasma pneumoniae HSV EBV CMV HHV6 Influenza Arboviruses	Aciclovir <30 weeks gestation= BD =20 mg/kg IV >30 weeks gestation to <3 months corrected age = TDS = 20 mg/kg IV 3 months–12 years = TDS = 20 mg/kg IV >12 years = TDS = 10 mg/kg IV 8H Consider adding azithromycin	Not advised

Steroids

1. Current evidence suggests that steroids may reduce the risk of hearing loss in bacterial meningitis.
2. Consider giving Dexamethasone to children > 2 months of age 15 minutes prior to parenteral antibiotics or, if this is not possible, within one hour of receiving their first dose of antibiotics: 0.15mg/kg IV. 
3. Consider giving steroids at the time of lumbar puncture if the clinical suspicion of meningitis is high.
4. Steroids should be ceased if a decision is made to cease antibiotic treatment for meningitis before 4 days (eg CSF microscopy not suggestive, CSF cultures negative at 48 hours).
5. Steroids are not recommended in neonates due to concern regarding effects on neurodevelopment

fluid resuscitation

1. Careful management of fluid and electrolyte balance is important in the treatment of meningitis. 
2. Over or under hydration are associated with adverse outcomes. 
3. Many children have increased antidiuretic hormone secretion, and some will have dehydration due to vomiting, poor fluid intake or septic shock. 
4. Hyponatramia occurs in about one third of children with meningitis, and may be due to increased ADH secretion, increased urine sodium losses, and excessive electrolyte-free water intake or administration
5. Fluid should be isonatraemic
6. Correct Hypovolemia with 20 mL/kg boluses 0/9%
7. Maintenance
   1. Plasma-Lyte 148 + 5% Glucose
   2. 0.9% sodium chloride + 5% Glucose
8. consider ICU admission

(https://www.rch.org.au/clinicalguide/guideline_index/Fluid_management_in_meningitis/)

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Complications

• Persistent fever after 4–6 days of treatment consider:
  • nosocomial infection
  • subdural effusion or empyema
  • cerebral abscess or parameningeal foci of ongoing infection
  • inadequate treatment
• Hearing impairment
• Neurodevelopmental impairment
• Multi-organ involvement due to primary pathogen or secondary to septic shock (eg hepatic or cardiac)
• Venous sinus thrombosis
• Seizures, subsequent epilepsy
• Permanent focal neurological deficit
• Hydrocephalus

Follow up

• Should have formal audiology assessment 6-8 weeks
• Monitor development

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PUBLIC HEALTH CONSIDERATIONS

• Neiserria meningitides – requires droplet precautions
• post-exposure prophylaxis needed for close contacts if <24h treatment with appropriate antibiotics
• Notification
  • All cases of presumed or confirmed Neisseria meningitidis disease should be urgently notified to the Department of Human Services by telephone
  • Haemophilus influenzae type b, and Streptococcus pneumoniae are also notifiable diseases.
• Contact chemoprophylaxis  

Organism	Those requiring prophylaxis	Antibiotic
N.meningitidis	Index Case (if treated only with penicillin) and all intimate, household or daycare contacts who have been exposed to Index Case within 10 days of onset. Any person who gave mouth-to-mouth resuscitation to the Index Case.	Rifampicin 10 mg/kg po 12 hourly (600 mg) for 2 days
		Infants < 1 month of ageRifampicin 5 mg/kg po 12 hourly for 2 days
		Pregnancy / contraindication to RifampicinCeftriaxone 125 mg (<12 y) / 250 mg (>12 y) mg im as a single dose or Ciprofloxacin 500 mg po as a single dose
S.pneumoniae	No increased risks to contacts	Nil
H influenzae type b	Index Case and all household contacts if household includes other children < 4 years of age who are not fully immunised. Index Case and all household contacts in households with any infants <12 months of age, regardless of immunisation statusIndex Case and all household contacts in households with a child 1 to 5 years of age who is inadequately immunised Index Case and all room contacts including staff in a child care group if Index Case attends > 18 hours / week and any contacts < 2 years of age who are inadequately immunised. (NB. Inadequately immunised children should be immunised.)	Rifampicin 20 mg/kg po as a single daily dose (600 mg) for 4 days
		Infants < 1 month of ageRifampicin 10 mg/kg po daily for 4 days
		Pregnancy / contraindication to Rifampicin Ceftriaxone 125 mg (<12 y) / 250 mg (>12 y) mg im as a single dose

Prevention

• Vaccination  – ACWY and Bexero
• Address risk factors
  • Living in dormitory or military barracks
  • Tobacco use or passive Tobacco exposure
  • Recent Upper Respiratory Infection/splenectomy/HIV

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Lumbar Puncture

Timing of Lumbar Puncture

• Preferred Timing: Ideally, a cerebrospinal fluid (CSF) specimen should be obtained before administering antibiotics to maximize diagnostic yield.
• Do Not Delay in Severe Cases: In critically ill children with signs of meningitis or sepsis, immediate initiation of antibiotic therapy should not be delayed, even if a CSF specimen has not yet been obtained.
• Avoid Lumbar Puncture: If a child is so unwell that antibiotics for meningitis will be administered regardless of CSF microscopy results, performing a lumbar puncture is not warranted.

Indications for Lumbar Puncture

• Suspected Meningitis or Encephalitis
• Suspected Subarachnoid Haemorrhage (when the CT scan is normal)

Contraindications to Lumbar Puncture

• Immediate Treatment with Dexamethasone and Antibiotics: Delay lumbar puncture for 1-2 days in critically ill children with the following conditions:
  • Coma: No purposeful response to painful stimuli (e.g., ear-lobe squeeze for up to 10 seconds). A child over 3 months should display purposeful behavior, such as pushing the examiner away.
  • Signs of Raised Intracranial Pressure (ICP):
    • Drowsiness
    • Diplopia
    • Abnormal pupillary responses
    • Motor posturing (unilateral or bilateral)
    • Papilloedema (note that papilloedema is a late and unreliable sign of raised ICP; a bulging fontanelle alone without other signs is not a contraindication)
  • Cardiovascular Compromise/ Shock
  • Respiratory Compromise
  • Focal Neurological Signs or Seizures
  • Recent Seizures (within 30 minutes or persistent altered consciousness after a seizure)
  • Coagulopathy or Thrombocytopenia
  • Local Infection at the proposed puncture site
  • Febrile Child with Purpura when meningococcal infection is suspected

Assessment Prior to Lumbar Puncture

• Contraindication Assessment: Thorough assessment for any signs of contraindications is essential before performing an LP.
• Use of CT Scans:
  • Indicated for Focal Neurological Signs: A CT scan may be performed when focal neurological signs are present.
  • Not Routinely Helpful: CT scans are generally not useful in most children with meningitis.
  • Limitations of a Normal CT: A normal CT scan does not exclude raised ICP, and herniation may still occur in its presence.
  • Do Not Delay Antibiotics: Do not postpone antibiotic therapy while waiting for a CT scan.

Potential Complications of Lumbar Puncture

• Failure to Obtain a Specimen / Need for Repeat LP / Traumatic Tap (common)
• Post-Dural Puncture Headache (occurs in 5-15% of cases)
• Transient or Persistent Paresthesiae/Numbness (rare)
• Respiratory Arrest Due to Positioning (very rare)
• Spinal Haematoma or Abscess (extremely rare)
• Tonsillar Herniation (extremely rare in the absence of contraindications listed above)

Proper assessment and timely decision-making are crucial for the effective management of children with suspected meningitis or other severe CNS infections.