Mednotes

L06 I&I Meningitis

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tagsinfection-and-immunity, lecture
aliasesL06 I&I Meningitis

14 min read

Overview

This lecture covers meningitis: its classification (infectious vs non-infectious, acute vs chronic, and by CSF cell type), the routes microorganisms use to reach the CNS, the age- and risk-group-specific aetiology of bacterial meningitis, the biology and virulence of Neisseria meningitidis as the key bacterial pathogen, the clinical presentation and complications, laboratory diagnosis via CSF analysis, and empiric and targeted antimicrobial treatment plus prevention through vaccination.

Classification and pathogenesis

  • Meningitis is inflammation of the meninges and CSF. The meninges and CSF are normally sterile, so finding any organism there is significant.
  • The CNS is highly sensitive to inflammation and oedema: raised intracranial pressure can cause pressure on the brainstem, herniation, and depression of respiratory/cardiac centres, so prompt diagnosis and therapy are crucial to avoid mortality and complications.
  • Disease can be acute (<4 weeks) or chronic (>4 weeks).
  • Causes are infectious (bacteria, viruses, fungi) or non-infectious (lymphoma/leukaemia, subarachnoid haemorrhage, drug reactions e.g. NSAIDs, autoimmunity, trauma, neurosurgery), and symptoms/presentation of the two can overlap; imaging (MRI/CT) is useful to distinguish them.
  • Classification by CSF findings:
    • Acute, purulent/pyogenic: bacterial; organisms usually from the normal microbiome (URT/GIT/UGT) and often capsulate; raised neutrophils in CSF.
    • Aseptic: viral; raised lymphocytes in CSF.
    • Chronic (granulomatous): bacterial (TB, syphilis) or fungal (Cryptococcus); raised lymphocytes in CSF.
  • Routes of infection into the CNS:
    • Haematogenous spread (most common): bacteraemia, viraemia, fungaemia.
    • Direct inoculation: trauma; iatrogenic (neurosurgery, CSF shunts, lumbar puncture).
    • Contiguous spread: local infection (otitis media, mastoiditis, sinusitis, dental infection); peripheral-to-central spread of viruses (e.g. herpes).
  • General pathogenesis: organisms cross the nasopharyngeal epithelium into the blood, are inoculated directly, or spread haematogenously from a distant infection site; they must then survive in the circulation long enough to cross the blood-brain barrier.
  • Risk factors: CSF shunts, spinal procedures, diabetes, neurosurgery, trauma, immunodeficiency, asplenia, age.
  • Viral meningitis (without encephalitis) is usually mild and self-limiting. It is preceded by a viraemic phase before organisms reach the CNS. Enteroviruses (e.g. Coxsackievirus) are the most common cause; herpes, mumps, and influenza viruses also cause it.
  • Meninges, outer to inner: dura mater -> subdural space -> arachnoid (with arachnoid trabeculae spanning to the pia) -> subarachnoid space (contains CSF and vessels) -> pia mater -> cerebral cortex.

Aetiology by age and risk group

  • Neonate (immature immune system): E. coli, Streptococcus agalactiae, S. epidermidis, Listeria monocytogenes, HSV.
  • <2 months (colonised at birth; transmission between babies or from adults): S. agalactiae, E. coli, L. monocytogenes.

  • 2 months-10 years (immune system developing, lacking opsonising antibodies): Haemophilus influenzae, N. meningitidis, Streptococcus pneumoniae, viruses.

  • Adolescent: N. meningitidis, viruses.
  • Adult: N. meningitidis, S. pneumoniae.
  • Elderly/immunocompromised: S. pneumoniae, L. monocytogenes, Gram-negative bacteria (e.g. E. coli).
  • HIV/AIDS or immunodeficiency: Cryptococcus (a yeast).
  • Trauma/iatrogenic: S. aureus, S. pyogenes, S. pneumoniae, Gram-negatives (e.g. Pseudomonas).
  • N. meningitidis is the single most important cause across ages 3 months to 50 years.

Neisseria meningitidis: biology, virulence and NZ epidemiology

  • Meningococcus is a Gram-negative diplococcus, found intracellularly within neutrophils in CSF; it is part of the respiratory microbiome in 5-15% of people.
  • Transmitted by respiratory aerosols from carrier to non-immune host; the recipient either becomes a carrier or develops disease, and only a small number of exposed people develop disease. It is highly transmissible, with carriage rates reaching ~80% during outbreaks and highest carriage in infants (3 months-1 year) and adolescents (>20%); these groups are most at risk.
  • Disease can present as meningitis, sepsis, or both; sepsis alone is often worse (>50% mortality), via circulatory collapse, DIC, thrombosis, ischaemia, and multi-organ dysfunction syndrome (MODS).
  • Virulence factors, organised by function:
    • Adhesins: Pili, Opa, Opc — attachment to epithelial/endothelial cells.
    • Porins: PorA, PorB — assist translocation across epithelia/endothelia into the bloodstream and across the blood-brain barrier.
    • Immune evasion (survival in bloodstream): capsule (prevents complement activation/opsonisation; sialic acid-based), sIgA protease, catalase.
    • LOS (lipooligosaccharide): released via membrane blebs in excess, which is proinflammatory.
  • Capsule: 13 serogroups exist; A, B, C, W and Y together cause >90% of infections. Serogroups B and W cause the most serious infections, with B the most common serogroup in NZ.
  • NZ epidemiology: an epidemic of N. meningitidis group B ran 1991-2007, with a cumulative burden of 6128 cases, 252 deaths and 1080 significant complications over the epidemic, peaking in 2001 at 648 cases (17.4 per 100,000), and disproportionately affected Maori and Pacific peoples; a vaccine campaign ran 2004-2008. Group B is still circulating (13% of cases in 2023).
  • NZ 2024: 43 cases notified (down from 59 in 2023), with 2 deaths; European/other and Maori groups had the highest incidence. B strain caused most infections in <1 year and 15-19 year age groups, accounting for 74% of identified isolates.
  • Figure 23 (meningococcal disease notifications, 2004-2023): notifications fell from 343 in 2004 to a low of 35 in 2020. The highest district notification rates were in Hawke’s Bay (2.7 per 100,000) and Canterbury (1.8 per 100,000). The highest age-specific rate was in infants <1 year (12.2 per 100,000), followed by 15-19 year-olds (3.7) and 1-4 year-olds (3.3). Females had a higher rate (1.4 per 100,000) than males (0.8 per 100,000). The highest ethnic-group rate was in Pacific peoples (3.1 per 100,000), followed by Maori (2.1).

A run of short fragmentary strings appears to the right of the Figure 23 charts in the transcript (an apparently cropped or overlapping data table/legend), too fragmentary to transcribe meaningfully; the notification and demographic figures above come from the (legible) chart and caption text, not from this cropped fragment.

Clinical features

  • Classic triad: fever, neck stiffness, headache — a good indicator but not always present (present in only 20-66% of cases).
  • High fever (>39degC) is the most common single feature, present in 95% of cases of acute bacterial meningitis.
  • Altered mental state (e.g. reduced level of consciousness) is described as an important indicator of meningitis.
  • Other features: photophobia, papilloedema (rare), seizures, lethargy, malaise, vomiting, diarrhoea, myalgia, arthralgia, cold/pale/mottled extremities, and sepsis/shock with circulatory collapse.
  • Rash: characteristic of N. meningitidis but not always present (50-80%). Petechiae appear early; purpura appears late and indicates severe disease (sepsis). The rash is non-blanching (glass/tumbler test: press a clear glass against the rash — if it does not fade through the glass, it is concerning and needs urgent medical review; if it fades it is less likely to be meningitis; repeat the test hourly as the rash can change).
  • Meningeal irritation signs: Kernig’s sign (with the hip flexed 90 degrees, the knee cannot be fully extended) and Brudzinski’s sign (passive neck flexion causes reflex flexion of both legs/thighs). These signs have low sensitivity, positive in <50% of cases.
  • Prodromal symptoms can resemble a non-specific respiratory tract infection (nausea, vomiting, fatigue, malaise, lethargy, cough, pharyngitis, headache, myalgia), so meningitis might not initially be considered.
  • Infants: symptoms may be non-specific (episodes of lethargy alternating with irritability, poor feeding); high-pitched cry and a bulging fontanelle are more specific signs.
  • Complications: death, amputation, hearing loss, blindness, epilepsy, cerebral palsy, cognitive issues, developmental delay. At surgery, the brain may be seen covered by purulent exudate with meninges thickened and opaque.
  • Risk groups: age (infants, elderly, and adolescents e.g. students), immunosuppression (diabetes, steroids, HIV, complement deficiencies), trauma/otitis media/sinusitis/dental infection, CSF shunts/neurosurgery, asplenia, and bacteraemia/fungaemia/viraemia.

Diagnosis

  • CSF is obtained by lumbar puncture, ideally before antimicrobials are given — but this must never be an excuse to delay therapy or avoid taking samples, since it takes 2-3 days of therapy to significantly alter CSF findings.
  • Normal CSF is clear, colourless and watery; visible turbidity indicates cells are present. Colour changes: yellow/orange/pink suggests blood (haemorrhage); green suggests pus.
  • CSF profile by cause:
    • Acute bacterial: raised WBC (neutrophil-predominant), decreased glucose, raised protein.
    • Aseptic (viral): raised WBC (lymphocyte-predominant), normal glucose, mildly raised protein.
  • CSF Gram stain directs initial antimicrobial therapy but is affected by prior antimicrobials. On Gram stain, N. meningitidis appears as Gram-negative diplococci (often seen intracellularly within neutrophils), while S. pneumoniae appears as Gram-positive diplococci — the two organisms are distinguished by this Gram-stain contrast.
  • Culture provides antimicrobial sensitivities (resistance is increasing) but is also affected by prior antimicrobials. Blood cultures are used to detect sepsis/bacteraemia.
  • PCR detects both bacteria and viruses, is rapid with high sensitivity and specificity, is not affected by prior antimicrobials, and needs only small CSF volumes (useful in neonates/children).
  • Test performance: Gram stain is positive in 60-90% of cases, falling to 40-60% if antimicrobials have already been given. Culture is positive in 75-80% of cases, falling to <50% with prior antimicrobials. A negative Gram stain or culture does not exclude a diagnosis of meningitis.

Treatment and prevention

  • Acute bacterial meningitis is a medical emergency: untreated infection or delayed treatment leads to significant mortality and complications, so prompt empiric antimicrobial therapy (before samples/results are available) is essential.
  • Pre-hospital treatment (NZ guidelines): IM ceftriaxone (or penicillin) for anyone with a haemorrhagic rash, or who is more than 30 minutes from a hospital.
  • Empiric hospital treatment: IV ceftriaxone.
  • Once the organism is identified:
    • N. meningitidis: IV ceftriaxone (decreased susceptibility/resistance to penicillin is possible); rifampicin is used for carriage/contacts.
    • H. influenzae: IV ceftriaxone.
    • S. pneumoniae: IV penicillin; IV vancomycin plus ceftriaxone is noted as a possible option if penicillin resistance is suspected, but the slides leave this as an open empiric choice (“empiric choice?”) rather than settled practice.
    • Neonates: IV penicillin/cephalosporin plus gentamicin (covers S. agalactiae, E. coli); add ampicillin if Listeria is suspected.
  • Steroids: dexamethasone may be beneficial for S. pneumoniae and H. influenzae meningitis, decreasing complications/mortality, possibly by affecting antimicrobial transport across the BBB (the slides pose this as a question rather than a confirmed mechanism).
  • Vaccination is recommended for risk groups, covering: S. pneumoniae (most common capsule types), H. influenzae b, and N. meningitidis (quadrivalent A/C/Y/W vaccine; serogroup B is now part of the vaccine schedule). Priority groups include infants and 13-25 year-olds in close-living situations (halls of residence/boarding schools); influenza vaccination is also mentioned.

Self-test

  1. Define meningitis and explain why finding any organism in the meninges/CSF is significant.
  2. Describe the three routes by which microorganisms reach the CNS, with an example for each.
  3. Distinguish acute (purulent), aseptic, and chronic (granulomatous) meningitis by their typical CSF cell type and causative organisms.
  4. List, in order from outer to inner, the layers of the meninges and the space that contains CSF.
  5. For each of the following groups, name the organism(s) most likely to cause meningitis: neonates, children >2 months to 10 years, adults, and elderly/immunocompromised patients.
  6. In which patient group does Cryptococcus meningitis typically occur?
  7. Describe the four functional classes of N. meningitidis virulence factors and what each does.
  8. Which N. meningitidis capsular serogroups cause most disease worldwide, and which is most common in New Zealand?
  9. A patient has fever, neck stiffness and headache. How reliable is this triad for diagnosing meningitis, and what single feature is most commonly present? What other feature is described as an important indicator?
  10. Describe the progression of the N. meningitidis rash and how the glass/tumbler test is used to assess it.
  11. What do Kernig’s and Brudzinski’s signs test for, and how sensitive are they?
  12. Describe the expected CSF appearance, WBC type, glucose, and protein findings in acute bacterial versus aseptic (viral) meningitis.
  13. On CSF Gram stain, how do N. meningitidis and S. pneumoniae differ in appearance, and where in the CSF is N. meningitidis typically seen?
  14. How does prior antimicrobial treatment affect the sensitivity of CSF Gram stain and culture, and what advantage does PCR have in this situation?
  15. Outline the empiric antimicrobial treatment for suspected bacterial meningitis before and after hospital arrival, and how treatment for N. meningitidis, S. pneumoniae, and neonates differs once identified.
  16. Summarise New Zealand’s meningococcal disease trends: describe the change in notifications from 2004 to 2020, and name the groups with the highest rates by district, age, sex, and ethnicity.
  17. Explain why prompt empiric treatment is emphasised even though it means treating before the causative organism is confirmed, linking together how patient age, clinical presentation, and CSF findings all feed into that initial treatment decision.

Answers

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