Meningococcal disease is caused by Neisseria meningitidis, a Gram-negative diplococcus which is not only a common bacterial commensal of the nasopharynx but can also cause septicaemia (meningococcaemia), meningitis or both. Meningococcal disease may also present with septic arthritis, osteomyelitis, conjunctivitis, endophthalmitis and chronic meningococcaemia. Meningococcal disease is the leading infectious cause of death in early childhood. It most commonly presents as bacterial meningitis (15% of cases of N. meningitidis) or septicaemia (25% of cases), or as a combination of the two presentations (60% of cases).
- N. meningitidis is usually found in the mucous membrane of the nose and throat of humans (no known animal reservoir) with carriage rates varying from 2% in the those aged under 5 to a peak of 25% in those aged 15-19 (in unimmunised populations).
- Carriage rates are greater in smokers, members of overcrowded households and military recruits.
- Asymptomatic nasopharyngeal carriage is transient and eventually resolves (after a period ranging from days to many months), leaving protective immunity against the organism.
- Infection is transmitted from person to person by droplets or secretions from the upper respiratory tract. The most likely source of infection of virulent strains appears to be household members or close friends who are asymptomatic carriers. Meningococci may spread from the nasopharynx to adjacent areas, occasionally causing pneumonia, sinusitis or otitis media.
- Meningococcal disease usually occurs within 1-14 days of acquisition.
- Most cases of meningococcal disease occur sporadically, with <5% of cases occurring in clusters.
Pathogenic forms possess a capsule that prevents phagocytosis:
- There are at least 13 serogroups.
- Serogroups A, B, C, Y and W cause most human meningococcal disease.
- Incidence of meningitis C has reduced dramatically since introduction of the vaccination programme in 1999.
- Colonisation with non-pathogenic Neisseria lactamica (common in preschool children) may confer protection against meningococcal disease.
The epidemiology of bacterial meningitis in the UK has changed dramatically in the period of two decades following the introduction of vaccines to control Haemophilus influenzae type b, serogroup C meningococcus and pneumococcal disease. Group B meningococcus is now the most common cause of bacterial meningitis (and septicaemia) in children and young people aged 3 months or older but this is likely to change with the introduction in 2015 of serogroup B vaccine.In the UK there has been a significant increase in infection due to serogroup W since 2009.
- Most infections occur during winter and early spring.
- Most cases occur below the age of 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.
- Most cases are sporadic, although outbreaks do occur, especially in adolescents.
- Most cases of invasive infection occur 3-5 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.
Features of bacterial meningitis include:
- Fever, headache.
- Stiff neck, back rigidity, bulging fontanelle (in infants), photophobia.
- Altered mental state, unconsciousness, toxic/moribund state.
- Non-blanching rash.
- Shock; signs of shock include:
- Toxic/moribund state; altered mental state/decreased conscious level.
- Unusual skin colour, capillary refill time more than two 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) and Brudziñski's sign (hips flex on bending the head forward).
- Paresis, focal neurological deficits (including cranial nerve involvement and abnormal pupils).
Meningococcal septicaemia and/or meningitis may specifically 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.
Presentation in children
- 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 13-22 hours.
- 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.
- The same study divided the clinical features into early, classic and late features, as follows below.
- Leg pain*.
- Abnormal skin colour.
- Breathing difficulty.
- Cold hands and feet.
- Haemorrhagic rash*: Early on, the rash may be nonspecific or absent. By the time the typical purpuric or petechial rash develops, the patient is gravely ill. Therefore, don't wait for the classic rash before admitting the patient.
- Neck stiffness* or pain.
- Bulging fontanelle.
- Confusion* or delirium.
*A follow-up study suggests that in a feverish child, in addition to the well-recognised 'red flag' symptoms of neck stiffness, rash and photophobia, the symptoms of leg pain and confusion also have a high likelihood ratio for meningococcal disease.
- Phone 999/112/911 to admit any patient with suspected bacterial meningitis or suspected meningococcal septicaemia to secondary care as an emergency.
- If there is a non-blanching rash, give parenteral antibiotics whilst waiting for the ambulance, if this will not delay admission to hospital:
- Give benzylpenicillin 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.
- If there is no rash, do not give parenteral antibiotics, unless rurality or adverse weather conditions make urgent admission impossible.
- 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.
- 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 must be treated with care to prevent false negative results. Close liaison with a microbiologist is required.
- Blood cultures.
- FBC (WCC), CRP, U&Es, renal function tests, LFTs.
- Blood test for polymerase chain reaction (PCR): perform whole blood real-time PCR testing - (EDTA sample) - for N. meningitidis to confirm a diagnosis of meningococcal disease and to serogroup.The earlier the blood is taken, the more likely it is to be positive, so consider testing an earlier blood sample if diagnosis was not considered at that time.
- 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.
- 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.
- Do not delay treatment in patients with signs of meningitis or septicaemia who have a petechial rash - start antibiotics immediately and supportive therapy as soon as possible (may require ITU) and investigate afterwards.
- If, at any point during the assessment, any of the following develop in a child or young person with a fever and a petechial rash, give IV ceftriaxone immediately (these children are at high risk of having meningococcal disease):
- Petechiae start to spread.
- The rash becomes purpuric.
- Signs of bacterial meningitis or meningococcal septicaemia develop.
- The child or young person appears ill.
- Choice of antibiotics in hospital should be guided by local protocols but the following are usually used:
- Ceftriaxone is usually given to those over 3 months
- Cefotaxime and amoxicillin are usually given to those under 3 months.
- Vancomycin is given in addition, 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 to be given to those aged under 3 months.
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.
- 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.
- Amputations and abnormal bone growth due to necrosis, have been seen increasingly, possibly as a result of increased survival rates from meningococcal disease.
- Skin complications (including scarring from necrosis).
- Psychosocial problems.
- Neurological and developmental problems.
- Chronic kidney disease.
- 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.
- 5-8% of cases show persistent problems such as headache, tiredness, sleeplessness, poor concentration problems and irritability, arthritis (10%) and cutaneous vasculitis.
- Mortality is now 2-11%. It is highest (10%) in neonates. Circulatory collapse is the primary cause of death in the developed world.
- 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.
Chemoprophylaxis for contacts
This should be offered as soon as possible after a case is confirmed:
- 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.
- Ciprofloxacin and rifampicin are both recommended by Public Health England (PHE) but ciprofloxacin is the preferred choice for most individuals.
- Ciprofloxacin can be used in all ages and in pregnancy; it is easily available in a single dose and does not interfere with oral contraceptives (but is contra-indicated if there has been previous sensitivity):
- Adults and children aged >12 years - 500 mg orally stat.
- Children aged 5-12 years - 250 mg orally stat.
- Children aged <5 years - 30 mg/kg up to a maximum of 125 mg orally stat.
- Rifampicin is no longer the drug of choice as, although it is licensed for chemoprophylaxis, it has several disadvantages including important drug interactions.
- If serotype of case is identified as type A, C, W or Y, contacts should also have subsequent meningococcal vaccine in addition to immediate chemoprophylaxis.
- Vaccination with serogroup C conjugate vaccine, part of the UK childhood vaccination programme. Also given to those aged 15-17 from 1999 (extended to those aged 20-24 from 2002) until 2015, when MenACWY introduced for this age group.
- Immunisation against group B meningococcus - introduced into the childhood vaccination programme in September 2015.
- A vaccine - quadrivalent (ACWY) conjugate vaccine (Menveo®; Nemenrix®) - is available against groups A, C, W and Y:
- This was introduced in August 2015 for those aged 17-18 years and older first-time university entrants up to the age of 25.
- MenACWY vaccine will be added to the routine adolescent schools programme (school year 9 or 10 - those aged 13-15) from Autumn 2015, as a direct replacement for the MenC vaccination.
- There will be a catch-up campaign for 2015/16 school year 11 students (those aged 15-16) through schools from January 2016.
- This vaccine is also 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.
- The quadrivalent vaccine is given to patients with asplenia, splenic dysfunction, immunosuppression or complement deficiency.
- Antibiotic prophylaxis for close contacts of index cases with ciprofloxacin or rifampicin (see 'Chemoprophylaxis for contacts', above).
Further reading and references
Stephens DS, Greenwood B, Brandtzaeg P; Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. Lancet. 2007 Jun 30369(9580):2196-210.
Hart CA, Thomson AP; Meningococcal disease and its management in children. BMJ. 2006 Sep 30333(7570):685-90.
Bacterial meningitis and meningococcal septicaemia: Management of bacterial meningitis and meningococcal septicaemia in children and young people younger than 16 years in primary and secondary care; NICE Clinical Guideline (last updated February 2015)
Meningococcal disease: guidance, data and analysis; Public Health England, July 2014
Meningococcal: the green book, chapter 22; Public Health England (July 2015)
Bilavsky E, Leibovitz E, Elkon-Tamir E, et al; The diagnostic accuracy of the 'classic meningeal signs' in children with suspected bacterial meningitis. Eur J Emerg Med. 2013 Oct20(5):361-3. doi: 10.1097/MEJ.0b013e3283585f20.
Thompson MJ, Ninis N, Perera R, et al; Clinical recognition of meningococcal disease in children and adolescents. Lancet. 2006 Feb 4367(9508):397-403.
Haj-Hassan TA, Thompson MJ, Mayon-White RT, et al; Which early 'red flag' symptoms identify children with meningococcal disease in primary care? Br J Gen Pract. 2011 Mar61(584):e97-104. doi: 10.3399/bjgp11X561131.
Brouwer MC, McIntyre P, Prasad K, et al; Corticosteroids for acute bacterial meningitis. Cochrane Database Syst Rev. 2013 Jun 46:CD004405. doi: 10.1002/14651858.CD004405.pub4.
Zalmanovici Trestioreanu A, Fraser A, Gafter-Gvili A, et al; Antibiotics for preventing meningococcal infections. Cochrane Database Syst Rev. 2013 Oct 2510:CD004785. doi: 10.1002/14651858.CD004785.pub5.
Introduction of Men B Immunisation for Infants, PHE and NHS England (letter), 22 June 2015; Public Health England
Meningococcal ACWY programme: information for healthcare professionals; Public Health England, 8 Jul 2015
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