Epidemiology

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. There is currently no licensed vaccine against serogroup B meningococcus, which is now the most common cause of bacterial meningitis (and septicaemia) in children and young people aged 3 months or older.^[3]

• Most infections occur during winter and early spring.^[5][4]
• Most cases occur below age 5 years and particularly during the first year of life. There is also a smaller peak at age 14-19 years. However, about one third of the cases of meningococcal disease occurs in adults.^[6]
• Most cases are sporadic, although outbreaks do occur, especially in adolescents.^[5]
• Most cases of invasive infection occur 2-4 days after acquiring the virulent strain, with invasion of the submucosa to reach capillaries and start the bacteraemia.
• Influenza A, asplenia and complement deficiencies predispose to infection.

Presentation^[3]

• Features of bacterial meningitis include:
  • Fever, headache.
  • Stiff neck, back rigidity, bulging fontanelle (in infants), photophobia.
  • Altered mental state, unconsciousness, toxic/moribund state.
  • Shock; signs of shock include:
    • Toxic/moribund state; altered mental state/decreased conscious level.
    • Unusual skin colour, capillary refill time more than 2 seconds; cold hands/feet.
    • Tachycardia and/or hypotension; respiratory symptoms or breathing difficulty.
    • Leg pain.
    • Poor urine output.
  • Kernig's sign (pain and resistance on passive knee extension with hips fully flexed).
  • Brudziñski's sign (hips flex on bending the head forward).
  • Paresis, focal neurological deficits (including cranial nerve involvement and abnormal pupils).
  • Seizures.
• Meningococcal meningitis and/or septicaemia may, in addition, present with capillary refill time more than 2 seconds, unusual skin colour, hypotension, leg pain and cold hands/feet.
• Meningococcal septicaemia without meningitis does not tend to present with stiff neck, back rigidity, bulging fontanelle, photophobia, Kernig's sign, Brudziñski's sign, paresis, focal neurological deficits or seizures.
• 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 (viral) infections presenting in this way
• Children and young people with the 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.

Prehospital management

• Transfer any patient with suspected bacterial meningitis or suspected meningococcal septicaemia to secondary care as an emergency by telephoning 999.^[3]
• Give benzylpenicillin whilst waiting for the ambulance unless there is history of immediate penicillin allergy after previous penicillin administration (eg difficulty in breathing, collapse, generalised itchy rash). Benzylpenicillin dose is 1,200 mg for adults, 600 mg if aged 1-9 years, 300 mg if aged <1 year.
• Cefotaxime may be used as an alternative.
• Antibiotics should be injected intravenously (IV) or intramuscularly (IM) in adults and IM in children. The recommended site of IM injection is the quadriceps muscle.^[1]
• Warn close family contacts that chemoprophylaxis may be required if meningococcal disease is confirmed (see 'Chemoprophylaxis for contacts', below).

Investigations in hospital

In order to confirm a diagnosis of meningitis, samples require to be treated with care to prevent false negative results. Close liaison with a microbiologist is required.

• Blood cultures.
• FBC, U&Es, renal function tests, LFTs.
• Investigations for disseminated intravascular coagulation (prothrombin time is elevated, activated partial thromboplastin time (aPTT) is elevated, platelet count is reduced and the fibrinogen level is low).
• Blood test for polymerase chain reaction (PCR); this is increasingly used for diagnosis, serogrouping and multilocus sequence typing.^[1] Perform whole blood real-time PCR testing - (EDTA sample) - for N. meningitidis to confirm a diagnosis of meningococcal disease.^[3]
• Pharyngeal swab (per-nasal if the patient is unable to co-operate).
• Lumbar puncture - once the patient is stable, and an assessment made to rule out raised intracranial pressure (may need a CT scan). Send cerebrospinal fluid for microscopy, culture, glucose and PCR.
• Aspirate from other sterile sites suspected of being infected (eg joints) for microscopy, culture and PCR.

Hospital management^[1]

• Antibiotics:
  • Do not delay treatment in acutely ill patients - start antibiotics and supportive therapy as soon as possible (may require ITU) and investigate afterwards.
  • Give IV ceftriaxone immediately to children and young people with a petechial rash if any of the following occur at any point during the assessment (these children are at high risk of having meningococcal disease):
    • Petechiae start to spread.
    • The rash becomes purpuric.
    • There are signs of bacterial meningitis or meningococcal septicaemia.
    • The child or young person appears ill.
  • Choice of antibiotics in hospital should be guided by local protocols but the following are usually used:
  • Cefotaxime and amoxicillin are usually given to those under 3 months.
  • Ceftriaxone is usually given to those over 3 months
  • Vancomycin is given also to those who have recently travelled outside the UK or have had prolonged or multiple exposure to antibiotics.
  • Traditionally, patients are treated for seven days, but three or four days of IV treatment have proved to be curative.
• Aggressive management of raised intracranial pressure reduces mortality.
• Fluids should not be restricted unless there is evidence of raised intracranial pressure.
• Most patients with fulminant meningococcal sepsis require dialysis; haemofiltration has been used to reduce oedema.
• Anticoagulants are sometimes given for patients with disseminated intravascular coagulation.
• Corticosteroids significantly reduce hearing loss and neurological sequelae, but there is no evidence that they reduce overall mortality. They are not usually given to those under three months.^[8]

Children and young people should be reviewed by a paediatrician, with the results of their hearing test 4-6 weeks after discharge from hospital, to discuss morbidities associated with their condition and to be offered referral to the appropriate services.^[3]

Complications

• Early complications - seizures, raised intracranial pressure, cerebral venous or sagittal sinus thrombosis, and hydrocephalus.
• In severe fulminant meningococcaemia - disseminated intravascular coagulation, adrenal haemorrhage and adrenal failure (Waterhouse-Friderichsen syndrome). Circulatory collapse and impaired renal and pulmonary function also occur.
• Late complications: communicating hydrocephalus (walking difficulty, cognitive impairment, incontinence), deafness (1-10% cases) which is usually irreversible. Children and young people with a severe or profound deafness should be assessed for cochlear implants as soon as they are fit to undergo testing.^[3]
• Amputations and abnormal bone growth due to necrosis have been increasingly seen recently as a result of meningococcal disease.^[2]
• Skin complications (including scarring from necrosis).
• Psychosocial problems.
• Neurological and developmental problems.
• Renal failure.
• Septic complications: septic arthritis, purulent pericarditis, endophthalmitis, pneumonia.
• Immune-complex complications, eg arthritis and pericarditis, tend to present several days after the onset of illness, when the patient is otherwise improving.^[1]
• 5-8% of cases show persistent problems such as headache, tiredness, sleeplessness, poor concentration problems and irritability, arthritis (10%), and cutaneous vasculitis.

Prognosis

• Mortality is now 2-11%. It is highest (10%) in neonates. Circulatory collapse is the primary cause of death in the developed world.^[1]
• Meningococcaemia is the more dangerous presentation, especially when leading to septic shock; however, meningitis is more likely to lead to neurodevelopmental complications.
• 15% of patients with meningococcal disease have long-term complications, including deafness and both major and minor neurodevelopmental impairments.^[2]

Chemoprophylaxis for contacts

This should be offered as soon as possible after a case is confirmed:^[4]

• To close contacts of cases, irrespective of vaccination status - for example, those who have had prolonged close contact with the case in a household-type setting during the seven days before onset of illness (ie living and/or sleeping in the same household, pupils in the same dormitory, boy/girlfriends, or university students sharing a kitchen in a hall of residence).
• Those who have had transient close contact with a case and have been directly exposed to large particle droplets/secretions from the respiratory tract of a case around the time of admission to hospital.
• Rifampicin is the drug of choice (but is contra-indicated if jaundice is present or there has been previous sensitivity):
  • Adults and children aged >12 years - 600 mg orally twice daily for two days.
  • Children aged 1-12 years - 10 mg/kg dose orally twice daily for two days.
  • Children aged <1 year - 5 mg/kg orally twice daily for two days.
• Rifampicin can be used in pregnancy (although caution is advised and ceftriaxone is preferred).
• Ciprofloxacin is often used when large numbers of contacts need prophylaxis.
• If serotype of case is identified as type A or C, contacts should also have subsequent meningococcal vaccine in addition to immediate chemoprophylaxis.

Prevention^[9]

• Vaccination with serogroup C conjugate vaccine, part of the UK vaccination programme for infants and 15-17 year-olds since 1999 (extended to 20-24 year-olds in 2002).^[10]
• A vaccine - quadrivalent (ACW135Y) conjugate vaccine (Menveo®) - is available against groups A, C, W135 and Y.
• This vaccine is given to those patients travelling to Saudi Arabia for pilgrims on Hajj and Umrah, and for other travellers in Hajj season. Vaccination is also recommended for travel to sub-Saharan Africa and certain other countries
• This is also given to patients with asplenia, splenic dysfunction, immunosuppression or complement deficiency.^[5]
• Antibiotic prophylaxis in close contacts of index cases with rifampicin or ciprofloxacin (see 'Chemoprophylaxis for contacts', above).