Bacterial meningitis and encephalitis

By the end of this note, the student will be able to distinguish, investigate, and clinically manage bacterial meningitis and encephalitis in a Kenyan ward setting; verify all drug choices and regimens against the Kenya MoH guidelines and local hospital formularies.

Definition

• Acute bacterial meningitis: Life-threatening acute purulent infection of the leptomeninges (pia mater, arachnoid mater) and the subarachnoid space, characterized by meningism and neutrophilic CSF pleocytosis.
• Encephalitis: Acute inflammation of the brain parenchyma itself, distinguished clinically from meningitis by early alteration in brain function (confusion, behavioral changes, focal neurological deficits, or seizures).
• Meningoencephalitis: Overlapping clinical syndrome showing features of both meningeal irritation and parenchymal damage.

Anatomy and physiology you need

• The Meninges: Dura mater (outer, tough fibrous layer), arachnoid mater (avascular middle mesh), and pia mater (vascular inner layer adherent to brain surface).
• Subarachnoid Space: Lies between the arachnoid and pia mater. It contains circulating cerebrospinal fluid (CSF) and major cerebral vessels. Infection here spreads rapidly throughout the brain and spinal axis because CSF lacks adequate local immune defenses (low complement and immunoglobulin levels).
• Blood-Brain Barrier (BBB): Formed by capillary endothelial cells with tight junctions (zonula occludens), a continuous basement membrane, and astrocyte end-feet (podocytes). It limits pathogen entry but also impedes hydrophilic antimicrobial penetration unless inflamed.
• CSF Dynamics and Monro-Kellie Hypothesis: Total cranial volume (brain, blood, CSF) is fixed. Purulent exudate obstructs arachnoid villi (impaired reabsorption) and choroid plexus inflammation impairs outflow, driving communicating or non-communicating hydrocephalus. This causes rapid, life-threatening rises in intracranial pressure (ICP).

Causes and risk factors

Common Etiological Agents

Kenyan Context and Local Risk Factors

• HIV/AIDS: Major predisposing factor in our wards. Advanced immunosuppression radically alters the differential: Cryptococcus neoformans and Mycobacterium tuberculosis (TBM) often outnumber classic acute pyogenic bacteria. Also predisposes to pneumococcal bacteremia and Listeria.
• Sickle Cell Disease (SCD): Functional asplenia impairs opsonization and clearance of encapsulated organisms, creating extreme vulnerability to Streptococcus pneumoniae and Neisseria meningitidis.
• **Cerebral Malaria (Plasmodium falciparum):** The critical tropical mimic of acute encephalitis in endemic areas (Western Kenya, Coast). Must be rapidly confirmed or excluded via blood film or rapid diagnostic test (RDT).
• Malnutrition and Chronic Alcohol Use: Depress cell-mediated immunity; alcohol misuse specifically increases the risk of pneumococcal pneumonia progressing to meningitis, as well as Listeria acquisition.
• Unvaccinated Status / Overcrowding: Inadequate coverage for Haemophilus influenzae type b (Hib) or pneumococcal conjugate vaccine (PCV), and overcrowded living conditions (informal settlements, boarding institutions) that facilitate respiratory droplet transmission of Neisseria meningitidis.

Pathophysiology

Bacterial Meningitis

Nasopharyngeal colonization by encapsulated pathogen $\rightarrow$ Secretion of IgA proteases enables mucosal attachment and invasion $\rightarrow$ Intravascular survival via antiphagocytic polysaccharide capsule $\rightarrow$ Crossing of the blood-brain barrier via cerebral capillaries or choroid plexus $\rightarrow$ Rapid bacterial replication in the subarachnoid space (low baseline complement/antibodies) $\rightarrow$ Bacterial autolysis releases cell-wall components (endotoxin/LPS, teichoic acid, peptidoglycans) $\rightarrow$ Activation of microglia and perivascular macrophages with release of TNF-$\alpha$, IL-1, and IL-6 $\rightarrow$ Increased BBB permeability, recruitment of polymorphonuclear neutrophils, and purulent exudate formation $\rightarrow$ Triple edema: vasogenic (BBB breakdown), cytotoxic (toxic leukocyte mediators), and interstitial (obstructed CSF outflow) $\rightarrow$ Marked rise in ICP $\rightarrow$ reduced cerebral perfusion pressure (CPP = MAP – ICP) $\rightarrow$ cerebral ischemia and herniation

Encephalitis (Viral / Parenchymal)

Inoculation (e.g., retrograde axonal transport via olfactory/trigeminal nerves in HSV-1, or hematogenous seeding in arboviruses) $\rightarrow$ Direct neurotropism and entry into parenchymal neurons and glial cells $\rightarrow$ Viral intracellular replication triggering cell lysis and apoptosis $\rightarrow$ Perivascular lymphocytic cuffing and glial nodules $\rightarrow$ Focal necrotizing hemorrhagic inflammation (predominantly temporal and inferior frontal lobes in HSV-1) $\rightarrow$ Parenchymal edema, microvascular thrombosis, neuronal dysfunction, and severe electrical instability (seizures)

Clinical features

History questions that matter

• Onset and tempo: Abrupt onset over hours to days suggests acute pyogenic meningitis. Subacute onset over 1–2 weeks points toward tuberculous or cryptococcal meningitis.
• Core symptoms: Inquire directly about severe, diffuse headache (meningeal stretching), fever (systemic pyrogenic cytokine release), photophobia (ciliary spasm from meningeal irritation), and neck stiffness.
• Encephalopathic features: Ask family about confusion, lethargy, behavioural changes, or memory deficits; early cortical dysfunction distinguishes encephalitis from pure meningitis.
• Seizures: Focal or generalised seizures indicate cortical involvement, cerebritis, or venous sinus thrombosis.
• Predisposing factors: Establish HIV status, ART history, prior tuberculosis or contact, sickle cell disease, recent otitis media, sinusitis, or base of skull trauma (rhinorrhoea/otorrhoea).

Examination findings and why each occurs

• Altered consciousness (GCS < 15): High intracranial pressure (ICP), toxic-metabolic encephalopathy, or direct parenchymal inflammation.
• Nuchal rigidity: Reflex spasm of extensor neck muscles to prevent painful traction on inflamed cervical spinal roots.
• Kernig sign: Resistance or pain on knee extension with hip flexed at 90°; traction on inflamed lumbosacral nerve roots.
• Brudzinski sign: Involuntary flexion of hips and knees upon passive neck flexion; protective shortening of the spinal axis to reduce dural tension.
• Focal neurological deficits: Hemiparesis, dysphasia, or gaze palsies; caused by focal cerebritis, ischaemic vasculitis, or secondary venous infarction.
• Cranial neuropathies (CN III, IV, VI, VII): Nerve compression or basal exudate entrapment. CN VI is particularly vulnerable as a false-localising sign of elevated ICP due to its long intracranial course.
• Cutaneous signs: Non-blanching purpuric or petechial rash signals Neisseria meningitidis bacteremia and microvascular thrombosis. Maculopapular or vesicular rashes suggest viral etiologies (e.g., VZV).
• Papilloedema: Axoplasmic flow stasis at the optic disc from prolonged raised ICP (often absent in hyperacute presentations).

Differential diagnosis

Investigations

Diagnosis and severity

Diagnostic synthesis

A definitive diagnosis of bacterial meningitis requires demonstration of a pathogenic bacterium or polymorphonuclear pleocytosis with depressed glucose and elevated protein in the CSF. In encephalitis, the diagnosis is clinical and supported by CSF showing lymphocytic pleocytosis, normal glucose, and temporal lobe involvement or diffuse swelling on neuroimaging or electroencephalography. Lumbar puncture must not be delayed unless neurofocal signs, new-onset seizures, unreactive pupils, or deep coma (GCS < 8) indicate space-occupying lesion or imminent uncal herniation; in such cases, obtain blood cultures and start empirical antimicrobial therapy immediately.

Severity assessment

• Critical severity indicators:
  • GCS < 8 or rapidly dropping score.
  • Signs of imminent herniation: Cushing triad (bradycardia, irregular respirations, severe hypertension).
  • Presence of status epilepticus.
  • Concomitant septic shock, disseminated intravascular coagulation (DIC), or extensive purpura fulminans.
  • Peripheral hypoperfusion and severe metabolic acidosis, which correlate with high mortality in Streptococcus pneumoniae and Neisseria meningitidis infections.

Management

Immediate Stabilisation:

• Airway: Assess patency. If GCS is low (typically <8), intubate and ventilate to protect the airway and prevent aspiration.
• Breathing: Ensure adequate oxygenation. Administer supplemental oxygen to maintain SpO2 >94%. Monitor respiratory rate and pattern.
• Circulation: Establish IV access (two large-bore cannulae). Assess blood pressure and heart rate. Treat hypotension with IV fluids (isotonic crystalloids) and vasopressors if necessary.
• Disability: Rapid neurological assessment (GCS, pupillary response, focal deficits). Treat seizures immediately with IV anticonvulsants.
• Exposure/Environment: Maintain normothermia.

Definitive Treatment:

• Empiric Antibiotics: Administer IV broad-spectrum antibiotics immediately after blood cultures are drawn and LP is considered (or deferred due to contraindications). Do not delay antibiotics for LP if there are contraindications or significant delay is anticipated.
  • Neonates (<1 month): Ampicillin plus an aminoglycoside (e.g., gentamicin) or a third-generation cephalosporin (e.g., cefotaxime).
  • Children (>1 month) and Adults: A third-generation cephalosporin (e.g., ceftriaxone or cefotaxime) plus vancomycin.
  • Immunocompromised/Elderly/Alcoholics: Consider adding ampicillin to cover Listeria monocytogenes.
  • Post-neurosurgery/Trauma/Shunt: Consider antipseudomonal beta-lactam (e.g., ceftazidime or meropenem) plus vancomycin.
• Corticosteroids: Dexamethasone should be given before or concurrently with the first dose of antibiotics, especially in suspected pneumococcal meningitis, to reduce inflammation and hearing loss. Continue for a few days.
• Specific Antibiotics (after culture results): Adjust antibiotics based on Gram stain and culture sensitivity.
  • Streptococcus pneumoniae: Penicillin G or ceftriaxone (if susceptible). If resistant, vancomycin plus ceftriaxone.
  • Neisseria meningitidis: Penicillin G or ceftriaxone.
  • Haemophilus influenzae: Ceftriaxone.
  • Listeria monocytogenes: Ampicillin or penicillin G, often with gentamicin.
  • Group B Streptococcus:* Penicillin G or ampicillin.
• Antiviral Agents: If viral encephalitis is suspected (e.g., HSV), initiate IV acyclovir empirically.
• Antituberculous Therapy: If tuberculous meningitis is suspected, initiate a multi-drug regimen (e.g., isoniazid, rifampicin, pyrazinamide, ethambutol) with corticosteroids.
• Antimalarials: If cerebral malaria is suspected, administer appropriate antimalarial agents.

Monitoring and Follow-up:

• Neurological Status: Frequent GCS, pupillary checks, motor strength, and seizure activity.
• Vital Signs: Continuous monitoring of blood pressure, heart rate, respiratory rate, temperature, and SpO2.
• Fluid Balance: Monitor input/output to prevent fluid overload or dehydration.
• Electrolytes: Monitor for SIADH (hyponatremia).
• Complications: Watch for seizures, hydrocephalus, cerebral edema, focal neurological deficits.
• Repeat LP: Consider if clinical improvement is not seen or if there is a relapse.
• Audiometry: Post-treatment, especially after pneumococcal meningitis.
• Rehabilitation: For persistent neurological deficits.

Contraindications and Safety:

• Lumbar Puncture: Contraindicated in signs of raised intracranial pressure (papilledema, focal neurological deficits, GCS <10, new-onset seizures) or coagulopathy. Perform CT scan before LP if these are present.
• Antibiotic Choice: Consider allergies.
• Corticosteroids: Use with caution in immunocompromised patients or those with active GI bleeding.
• Fluid Management: Avoid overhydration, which can worsen cerebral edema.

Complications and Prognosis

Complications:

• Neurological:
  • Seizures (early or late)
  • Hydrocephalus (communicating or non-communicating)
  • Cerebral edema and raised ICP
  • Focal neurological deficits (hemiparesis, cranial nerve palsies, especially 3rd, 6th, 7th, 8th)
  • Hearing loss (sensorineural, common with pneumococcal meningitis)
  • Cognitive impairment, learning difficulties, behavioral changes
  • Cerebral venous thrombosis, stroke
  • Brain abscess, subdural empyema
• Systemic:
  • SIADH (Syndrome of Inappropriate Antidiuretic Hormone secretion)
  • Sepsis, septic shock, DIC (Disseminated Intravascular Coagulation), especially with meningococcal disease (Waterhouse-Friderichsen syndrome)
  • Arthritis, pericarditis, myocarditis (less common)
  • Renal failure

Prognosis:

• Varies significantly with the causative organism, patient age, immune status, speed of diagnosis, and initiation of appropriate treatment.
• Bacterial meningitis: Mortality remains significant (5-20% in adults, higher in neonates and elderly).
• Poor prognostic factors: Extremes of age, delayed presentation, low GCS on admission, presence of seizures, focal neurological deficits, shock, specific organisms (e.g., Listeria, resistant S. pneumoniae).
• Long-term neurological sequelae occur in 15-30% of survivors.

High-yield exam points

• Look-alike conditions: Subarachnoid hemorrhage (thunderclap headache, meningism, but LP shows xanthochromia), cerebral malaria (fever, altered consciousness, seizures, but peripheral smear positive), severe sepsis with encephalopathy (altered mental status, but no meningism), viral meningitis (milder, self-limiting).
• Commonest wrong first steps: Delaying antibiotics while awaiting LP results in a patient with suspected bacterial meningitis and contraindications to LP or significant delay. Not giving dexamethasone with the first dose of antibiotics.
• Bedside questions:
  • "What are you looking for on this patient's skin?" (Petechial/purpuric rash of meningococcemia, track marks in IV drug users, signs of trauma).
  • "How do you assess for meningism?" (Neck stiffness, Kernig's, Brudzinski's signs).
  • "What are the absolute contraindications to LP?" (Signs of raised ICP, focal neurological deficits, GCS <10, new-onset seizures, coagulopathy).
  • "Why is dexamethasone given?" (To reduce inflammation and neurological sequelae, especially hearing loss, in pneumococcal meningitis).
  • "What are the immediate steps if this patient has a seizure?" (Protect airway, administer IV anticonvulsants, check glucose).

Clinical case

A 3-year-old boy is brought to the emergency department with a 2-day history of fever, irritability, poor feeding, and repeated vomiting. His mother reports he has been drowsy and had a brief generalized seizure at home. On examination, he is febrile (39.5°C), lethargic but rousable, with a GCS of 11/15. He has neck stiffness and a positive Brudzinski's sign. There are no rashes.

Question 1

What is the most appropriate immediate next step in management after initial stabilization?

A. Perform a CT scan of the head. B. Administer empiric intravenous antibiotics and dexamethasone. C. Perform a lumbar puncture. D. Send blood for full blood count and electrolytes.

Answer: B. Administer empiric intravenous antibiotics and dexamethasone. Explanation: Given the high suspicion of bacterial meningitis and the presence of meningism, immediate administration of empiric antibiotics and corticosteroids is crucial to improve outcomes and reduce mortality, even before definitive diagnosis.

Question 2

Which of the following CSF findings would be most consistent with bacterial meningitis in this child?

A. Clear fluid, elevated protein, normal glucose, lymphocytic pleocytosis. B. Turbid fluid, very high protein, very low glucose, neutrophilic pleocytosis. C. Clear fluid, normal protein, normal glucose, no cells. D. Xanthochromic fluid, elevated protein, normal glucose, lymphocytic pleocytosis.

Answer: B. Turbid fluid, very high protein, very low glucose, neutrophilic pleocytosis. Explanation: Bacterial meningitis typically presents with turbid CSF, significantly elevated protein, markedly reduced glucose (due to bacterial consumption), and a predominance of neutrophils (polymorphonuclear cells).

Question 3

The child is started on appropriate treatment. On day 3, he develops new-onset focal neurological deficits and his GCS drops further. What complication should be immediately considered?

A. Syndrome of Inappropriate Antidiuretic Hormone (SIADH). B. Drug-induced encephalopathy. C. Hydrocephalus or cerebral venous thrombosis. D. Otitis media.

Answer: C. Hydrocephalus or cerebral venous thrombosis. Explanation: New-onset focal neurological deficits and worsening GCS in a patient with bacterial meningitis suggest a serious intracranial complication such as hydrocephalus (due to impaired CSF flow), cerebral venous thrombosis, or even a developing brain abscess. These require urgent imaging (CT or MRI).

Practice questions

Question 1

A 25-year-old HIV-positive patient presents with fever, severe headache, neck stiffness, and photophobia. CSF analysis shows clear fluid, protein 0.8 g/L (normal <0.45), glucose 2.5 mmol/L (serum glucose 5.0 mmol/L), and 200 cells/µL, 90% lymphocytes. What is the most likely diagnosis?

A. Bacterial meningitis B. Viral meningitis C. Tuberculous meningitis D. Cryptococcal meningitis

Answer: D. Cryptococcal meningitis Explanation: In an HIV-positive patient, lymphocytic pleocytosis, elevated protein, and moderately low glucose in CSF are highly suggestive of cryptococcal meningitis, which is common in this population.

Question 2

A 6-month-old infant presents with fever, irritability, and bulging fontanelle. Suspecting bacterial meningitis, a lumbar puncture is performed. Which of the following findings would prompt immediate administration of dexamethasone along with antibiotics?

A. CSF Gram stain showing Gram-positive cocci in chains. B. CSF Gram stain showing Gram-negative rods. C. CSF Gram stain showing no organisms. D. Dexamethasone is contraindicated in infants.

Answer: A. CSF Gram stain showing Gram-positive cocci in chains. Explanation: Dexamethasone is recommended to reduce neurological sequelae, particularly hearing loss, especially in suspected pneumococcal meningitis (Gram-positive cocci in chains).

Question 3

A 40-year-old man with suspected bacterial meningitis has a GCS of 7/15 and bilateral papilledema. What is the most appropriate next step?

A. Proceed directly to lumbar puncture for CSF analysis. B. Administer empiric antibiotics and dexamethasone, then perform a CT scan of the head. C. Administer empiric antibiotics and dexamethasone, then perform lumbar puncture. D. Perform a CT scan of the head, then administer antibiotics.

Answer: B. Administer empiric antibiotics and dexamethasone, then perform a CT scan of the head. Explanation: Papilledema and low GCS are signs of raised intracranial pressure, which contraindicate immediate LP. Antibiotics and dexamethasone should not be delayed, so they are given first, followed by a CT scan to rule out a mass lesion before considering LP.

Question 4

Which of the following is a common long-term neurological complication of bacterial meningitis, particularly in children?

A. Parkinsonism B. Amyotrophic lateral sclerosis C. Sensorineural hearing loss D. Multiple sclerosis

Answer: C. Sensorineural hearing loss Explanation: Sensorineural hearing loss is a well-recognized and common long-term complication of bacterial meningitis, especially pneumococcal meningitis, and often necessitates audiological follow-up.

Question 5

A patient with bacterial meningitis is receiving appropriate IV antibiotics. On day 2, their serum sodium drops to 125 mmol/L, and urine output is low despite adequate fluid intake. What is the most likely cause?

A. Dehydration B. Renal failure C. Syndrome of Inappropriate Antidiuretic Hormone (SIADH) D. Adrenal insufficiency

Answer: C. Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Explanation: Hyponatremia with low urine output and adequate fluid intake in the context of meningitis strongly suggests SIADH, a common complication due to increased ADH secretion from hypothalamic involvement or stress.

Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.