Epidemiology

• Meningitis occurs in people of all age groups, but infants, young children and the elderly are more predisposed to meningitis.³
• Viral meningitis is the most common cause.
• The incidence of bacterial meningitis is 2-5 per 100,000.⁴
• The epidemiology of bacterial meningitis in the UK has changed dramatically in the past two decades following the introduction of vaccines to control Haemophilus influenzae type b, serogroup C meningococcus and pneumococcal disease.²
• There is currently no licensed vaccine against serogroup B meningococcus, which is now the most common cause of bacterial meningitis (and septicaemia) in those aged 3 months to 16 years.²

Risk factors

• Patients with CSF shunts or dural defects (e.g. staphylococcal).
• Patients having spinal procedures (e.g. spinal anaesthetics) are at increased risk and Pseudomonas spp. may then be the cause.
• Other risk factors include bacterial endocarditis, diabetes mellitus, alcoholism and cirrhosis, intravenous drug abuse, renal insufficiency, adrenal insufficiency, malignancy (increased risk of listerial infection), hypoparathyroidism, thalassaemia major and cystic fibrosis.
• Splenectomy and sickle cell disease increase the risk of meningitis secondary to encapsulated organisms.
• Crowding (e.g. military recruits and college students) increases the risk of outbreaks of meningococcal meningitis.

Causes

Meningitis can be caused by any bacteria but the most common bacterial causes are:
• Neonates: group B streptococci, Listeria monocytogenes, Escherichia coli.
• Infants and young children: H. influenzae type b if younger than 4 years and unvaccinated, Neisseria meningitidis, Streptococcus pneumoniae.
• Adults and older children: S. pneumoniae, H. influenzae type b, N. meningitidis, Gram-negative bacilli, staphylococci, streptococci and L. monocytogenes.
• Elderly and immunocompromised: S. pneumoniae, L. monocytogenes, tuberculosis (TB), Gram-negative organisms.
• Hospital-acquired and post-traumatic meningitis (may often be multidrug-resistant), Klebsiella pneumoniae, E.coli, Pseudomonas aeruginosa, Staphylococcus aureus.
• N. meningitidis: usually local outbreaks among young adults; increased incidence in late winter or early spring. Meningococcal meningitis is endemic in parts of Africa, India and other developing nations. Periodic epidemics occur in sub-Saharan Africa as well as among religious pilgrims travelling to Saudi Arabia for the Hajj.
• Syphilis and TB are rare causes but are increasing in association with HIV infection.

Neonatal meningitis⁵

See also separate general articles Congenital Infections in Neonates and Perinatal and Neonatal Infection.

• Neonates are at greater risk of meningitis. Risk factors for the development of meningitis include low birthweight (below 2,500 g), premature delivery, premature rupture of membranes, traumatic delivery, fetal hypoxia and maternal peripartum infection.
• Intrapartum prophylactic antibiotics in pregnant mothers who carry, or who are at risk of colonising group B streptococci, has been effective in reducing the risk of neonatal group B streptococcal meningitis.
• Caesarean section reduces the risk of transmission of herpes simplex virus (HSV).
• The initial presentation is usually nonspecific with features including raised or unstable temperature, respiratory distress, episodes of apnoea and bradycardia, hypotension, feeding difficulty, irritability and reduced activity.
• Meningitis should therefore be considered and included in the urgent investigations of any acutely ill neonate.
• In developed countries, the rate of mortality from bacterial meningitis among neonates has decreased but there has not been a significant decrease in long-term complications such as cerebral palsy, learning disability, seizures and hearing impairment.
• Mortality following HSV infection of the central nervous system is 15%. HSV-1 and HSV-2 have the same risk of mortality but HSV-2 is more often associated with long-term complications such as cerebral palsy, mental retardation, seizures, microcephaly and visual impairment.

Aseptic meningitis

CSF has cells but is Gram-stain negative and no bacteria can be cultured on standard media. Causes include:

• Partly treated bacterial meningitis.
• Viral infection, e.g. mumps, echovirus, Coxsackie, herpes simplex virus (HSV)⁵ and herpes zoster virus, HIV, measles, influenza, arboviruses. See separate Viral Meningitis article.
• Fungal infection: fungal meningitis is rare, but can be life threatening. People with immunodeficiency (e.g. AIDS, leukaemia, immunosuppressant medication) are at higher risk. Fungal causes of meningitis include Cryptococcus, Histoplasma and Coccidioides.
• Parasites, e.g. eosinophilic meningitis caused by angiostrongyliasis
• Other possible causative organisms include atypical TB, syphilis, Lyme disease, leptospirosis, listeriosis and brucellosis.
• Kawasaki disease.
• Mollaret's meningitis.

Noninfective meningitis

Meningeal inflammation can be caused by meningeal infiltration by:

• Malignant cells (leukaemia, lymphoma, other tumours).
• Chemical meningitis (intrathecal drugs, contaminants).
• Drugs (non-steroidal anti-inflammatory drugs (NSAIDS), trimethoprim).
• Sarcoidosis.
• Systemic lupus erythematosus.
• Behçet's disease.

Presentation

See also separate articles Ill and Feverish Child and Fever and Night Sweats.

• Clinical presentation of meningitis may include:²
  • Fever, headache.
  • Stiff neck (generally not present in children under the age of one year or in patients with altered mental state), back rigidity, bulging fontanelle (in infants), photophobia, opisthotonus (if severe).
  • Altered mental state, unconsciousness, toxic/moribund state.
  • Shock: signs of shock include tachycardia and/or hypotension, respiratory distress, altered mental state and poor urine output.
  • Kernig's sign (pain and resistance on passive knee extension with hips fully flexed).
  • Brudzinski's sign (hips flex on bending the head forward).
  • Paresis, focal neurological deficits (including cranial nerve involvement and abnormal pupils).
  • Seizures.
• Viral meningitis may be clinically indistinguishable from bacterial meningitis but features may be more mild and complications (e.g. focal neurological deficits) less frequent. Any person presenting with suspected meningitis should therefore be managed as having bacterial meningitis until proved otherwise.
• Classic symptoms are not evident in infants and also not often seen in the elderly.
• Some children and young people will present with mostly nonspecific symptoms or signs and the conditions may be difficult to distinguish from other less important infections presenting in this way. Children and young people with more specific symptoms and signs are more likely to have bacterial meningitis or meningococcal septicaemia and the symptoms and signs may become more severe and more specific over time.²
• Approximately 25% of patients with bacterial meningitis present acutely within 24 hours of onset of symptoms. Other patients with bacterial meningitis and most patients with viral meningitis present with subacute neurological symptoms developing over 1-7 days. Chronic symptoms lasting longer than one week suggest meningitis caused by some viruses as well as TB, syphilis or fungi.

Individual symptoms have low diagnostic accuracy. Absence of fever, neck stiffness, and altered mental status makes the diagnosis of meningitis much less likely. A study of children aged 16 years or younger with meningococcal disease found that classical signs such as haemorrhagic rash, meningism and impaired consciousness did not tend to appear until after 13 to 22 hours. However, more nonspecific features such as leg pain, cold hands and feet and abnormal skin colour appeared much earlier with a median onset of 7-12 hours. These earlier features are thus very important in early diagnosis and therefore earlier initiation of potentially life-saving treatment.⁷

Differential diagnosis

• Other causes of pyrexia and severe infection.
• Intracranial abscess.
• Other causes of altered mental state and coma, e.g. encephalitis, subarachnoid haemorrhage, brain tumours.

Investigations

Investigations must not delay treatment.

Lumbar puncture

See separate articles Lumbar Puncture (LP) and Cerebrospinal Fluid for normal values and interpretation of abnormal CSF findings.

• Perform LP immediately provided there are no signs of raised intracranial pressure (reduced consciousness, very bad headache, frequent fits) or focal neurology. Beware signs of impending brain herniation (abnormal postures or breathing, dilated pupils, doll's eyes reflexes, papilloedema). If any doubt do emergency CT first (but one study suggested it is a poor predictor of herniation).⁸
  • Send a minimum of 3 bottles of CSF for Gram stain, Ziehl-Neelsen stain (TB), cytology, virology, glucose, protein, culture, rapid antigen screen or polymerase chain reaction (PCR) if available and India ink for cryptococci.
  • CSF may be normal in the early stages of meningitis so repeat the LP if symptoms and signs persist.

Other investigations

• Blood cultures should be sent before initiating antibiotic therapy.⁴
• Blood glucose (to compare with CSF).
• Full blood count, renal function tests
• Coagulation profile: especially if disseminated intravascular coagulation is suspected.
• Chest X-ray (lung abscess).
• Culture urine, nasal swabs and stool (virology).
• Perform whole blood real-time PCR testing (EDTA sample) for N. meningitidis to confirm a diagnosis of meningococcal disease.²
• CT scan can rule out a mass lesion or hydrocephalus. CT scan if there is history of head injury, altered mental state, focal neurological deficits or concern regarding raised intracranial pressure before LP.
• Other possible investigations:
  • Serum cryptococcal antigen, especially if the baseline is known (less diagnostic than India ink and CSF cryptococcal antigen).
  • Serology of blood, urine, and CSF for specific bacterial antigens is occasionally recommended if there is diagnostic doubt or in patients with partially treated meningitis.
  • Serum test for syphilis if neurosyphilis is suspected.

Management

Management includes supportive treatment (including fluids, antipyretics, antiemetics), treatment of the causative organism and treatment of any complications, e.g. seizures, raised intracranial pressure. See also the articles on specific infections for management of rarer causes of meningitis such as tuberculosis, fungi and parasites.

Management of viral meningitis

• The general principles of management for all viral meningitis includes supportive therapy, e.g. analgesia, antipyretics, nutritional support and hydration.
• Enteroviral meningitis: usually self-limiting and no specific therapy is required unless there is hypogammaglobulinaemia (immunoglobulins required).
• Acyclovir is considered beneficial in treating herpetic viral infections but only if given very early in the course of the infection, and evidence for benefit is limited. Intravenous acyclovir should be started immediately if there is any suspicion of herpes simplex encephalitis.
• Ganciclovir is effective for cytomegalovirus (CMV) infections but, because of toxicity, should be reserved for severe cases with positive CMV culture or when a congenital infection or an AIDS-related infection is likely.⁹

Management of bacterial meningitis²

• Management includes supportive treatment with analgesia, antipyretics, nutritional support and hydration.
• Do not restrict fluids unless there is evidence of raised intracranial pressure or increased antidiuretic hormone secretion.²
• The choice of antibiotics and the duration of therapy should be guided by the microbiological diagnosis but initial 'blind' antibiotic therapy must be started immediately.
• Corticosteroids:
  • Dexamethasone should be administered with, or shortly before, the first dose of antibiotic in suspected cases of bacterial meningitis.⁴
  • Corticosteroids given to patients of all ages with bacterial meningitis significantly reduce hearing loss and neurological sequelae, but there is no evidence that they reduce overall mortality.¹⁰
  • Avoid dexamethasone in patients with septic shock, if immunocompromised, or in patients with meningitis following surgery.¹¹
• The listed antibiotic drug regimes are based on current British National Formulary (BNF) guidance:¹¹

• Third generation cephalosporin (cefotaxime or ceftriaxone) is often used as empirical treatment before identification of the causative organism.
• Amoxicillin should be added if listeriosis is suspected and particularly for infants under three months old, those aged over 50 years and immunocompromised individuals.⁸

• Benzylpenicillin or cefotaxime for at least 7 days (use chloramphenicol instead if there is a history of anaphylaxis to penicillin or to cephalosporins).
• Give rifampicin for 2 days to patients treated with benzylpenicillin or chloramphenicol in order to eliminate nasopharyngeal carriage.
• Prevention of secondary case of meningococcal meningitis:
  • Rifampicin 600 mg every 12 hours for 2 days (child 10 mg/kg, or 5 mg/kg if aged under 1 year) every 12 hours for 2 days.
  • Or ciprofloxacin (not licensed for this indication) 500 mg as a single dose (child 5-12 years 250 mg).
  • Or IM ceftriaxone (not licensed for this indication but the preferred choice for pregnant women) 250 mg as a single dose (child aged under 12 years 125 mg).

• Treat with cefotaxime for 10-14 days.
• Use benzylpenicillin if the organism is penicillin-sensitive.
• Add vancomycin and, if necessary, rifampicin if the organism is resistant to penicillin and cephalosporins.

• Treat with cefotaxime for at least 10 days; use chloramphenicol instead if there is history of anaphylaxis to penicillin or cephalosporins, or if the organism is resistant to cefotaxime.
• Give rifampicin for patients with H. influenzae type b infection for 4 days before discharge.
• Prevention of secondary case of H. influenzae type b disease:
  • Rifampicin 600 mg once daily for 4 days (child aged 1-3 months 10 mg/kg once-daily for 4 days; aged over 3 months 20 mg/kg once-daily for 4 days).

• Treat for 14 days with benzylpenicillin and gentamicin, or cefotaxime alone.

• Treat for 10-14 days with amoxicillin and gentamicin.

• See also separate article Rising Intracranial Pressure.
• Patients should be considered for urgent admission to intensive care and for elective intubation and ventilation.¹²

Complications

• Immediate: septic shock, including disseminated intravascular coagulation, coma with loss of protective airway reflexes, seizures (30-40% of children, 20-30% of adults), cerebral oedema and raised intracranial pressure, septic arthritis, pericardial effusion, and haemolytic anaemia (H. influenzae).
• Subdural effusions: reported in 40% of children aged 1-18 months with bacterial meningitis. Risk factors include young age, rapid onset of illness, low peripheral white cell count and high CSF protein.
• Syndrome of inappropriate antidiuretic hormone secretion (SIADH).
• Seizures: occur more commonly during the acute stage of the disease.
• Delayed: decreased hearing or deafness, other cranial nerve dysfunction, multiple seizures, focal paralysis, subdural effusions, hydrocephalus, intellectual deficits, ataxia, blindness, Waterhouse-Friderichsen syndrome, and peripheral gangrene.

Prognosis

• Prognosis depends on the pathogen, the patient's age and condition, and the severity of acute illness.
• Patients with severe neurological impairment on presentation or with extremely rapid onset of illness, even if treated immediately, have a 50-90% mortality rate and an even higher rate of morbidity.
• Pneumococcal meningitis has the highest rates of mortality (21%) and morbidity (15%).
• Meningococcal disease has a better prognosis when meningitis accompanies the septicaemia than when it doesn't.

Prevention

See separate articles Immunisation Schedule (UK), Hib Vaccination, Meningococcal Vaccines and Pneumococcal Vaccine.

• Vaccination against H. influenzae type b, meningococcus group C and S. pneumoniae.¹³
• Appropriate prophylaxis of people in close contact with those diagnosed.

Document references

1. Lazoff M; Meningitis, eMedicine, Feb 2010
2. Bacterial meningitis and meningococcal septicaemia, NICE Clinical Guideline (June 2010); The management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care
3. Razonable RR et al; Meningitis, eMedicine, Jun 2010
4. Chaudhuri A, Martinez-Martin P, Kennedy PG, et al; EFNS guideline on the management of community-acquired bacterial meningitis: Eur J Neurol. 2008 Jul;15(7):649-59. [abstract]
5. Dredge DC et al; Neonatal Meningitis, eMedicine, Jan 2010
6. Management of invasive meningococcal disease in children and young people, Scottish Intercollegiate Guidelines Network - SIGN (May 2008)
7. Thompson MJ, Ninis N, Perera R, et al; Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006 Feb 4;367(9508):397-403. [abstract]
8. Meningitis Trust; The Meningitis Resource Pack, 2003
9. Vokshoor A et al; Viral Meningitis, eMedicine, Oct 2009
10. Brouwer MC, McIntyre P, de Gans J, et al; Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2010 Sep 8;9:CD004405. [abstract]
11. British National Formulary; 59th Edition (March 2010) British Medical Association and Royal Pharmaceutical Society of Great Britain, London.
12. Heyderman RS; Early management of suspected bacterial meningitis and meningococcal septicaemia in immunocompetent adults--second edition. J Infect. 2005 Jun;50(5):373-4. [abstract]
13. British National Formulary; 61st Edition (March 2011) British Medical Association and Royal Pharmaceutical Society of Great Britain, London (link to current BNF)

Internet and further reading

• Meningitis Research Foundation; Home page
• Meningococcal disease, Health Protection Agency
• Management of Infection - Guidance for Primary Care, Health Protection Agency, various dates; (including diagnosis - quick reference guides)