Meningococcal Disease (Neisseria Meningiditis)

• It is usually found in the mucous membrane of the nose and throat of humans³ (no known animal reservoir) with carriage rates varying from 2% in the under fives to a peak of 25% in 15-19 year olds (in unimmunised populations).⁴
• Carriage rates are greater in smokers, 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.¹
• 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.
• Meningococcal disease usually occurs within 1-14 days of acquisition.¹
• Most cases of meningococcal disease occur sporadically, with <5% of cases occurring in clusters.

Pathogenic forms possess a capsule that prevents phagocytosis:

• These are divided into 13 serogroups, of which 9 cause invasive disease (A, B, C (C1 , C1-), X, Y, W-135, Z, and L).
• 4 serotypes are known to cause epidemics: A, B, C and W135.
• In the UK in 1996-2000, group B accounted for 59% of all infections, and group C 36% (now greatly reduced by vaccination).
• Colonisation with non-pathogenic Neisseria lactamica (common in preschool children) may confer protection against meningococcal disease.

Meningococcal disease is the most common infectious cause of death in childhood in developed countries.
• UK rates of invasive disease are 2-6 per 100,000 with approximately 10% fatality.
• Large scale epidemics can occur in the developing world, mainly in sub-Saharan Africa but also in Russia and China, due mainly to group A.¹
• Most infections occur during winter and early spring.^3,5
• Most cases occur below age 5 years and particularly during 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 occur 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.

• The classic features of meningococcaemia are the abrupt onset and rapid progression of a non-blanching haemorrhagic rash (may be petechial only) associated with fever.²
• Meningococcal disease may also present with circulatory collapse and meningitis.¹
• Meningococcaemia may present without a rash, making rapid diagnosis particularly difficult.
• Meningococcaemia may present with red maculae with a diameter more than 1 cm with no other signs.¹
• In the very young in particular, the onset may be insidious and classic symptoms absent. Consider the diagnosis when there is vomiting, pyrexia, irritability and (if still patent, raised anterior fontanelle tension).
• It is obviously extremely difficult to diagnose early cases. Where the diagnosis is only a remote possibility when symptoms are mild and non specific, ensure the parents or friends are aware of the signs to look for, and ensure that there is adequate follow-up - ideally arrange to review the child in an hour or two, earlier if the patient becomes difficult to rouse, a rash develops or the child begins crying in an odd (weak) way.
• In severe illness, septicaemic features are often more apparent than features of meningism. The prognosis in meningococcal disease is improved if meningism is present.

Transient meningococcaemia¹

• Causes fever and a non-specific viral rash, which can both disappear within 2-5 days without treatment.

Chronic meningococcaemia¹

• Rare but can last for weeks or months.
• Causes intermittent fever, arthralgia and a non-specific maculopapular rash.
• Symptoms may disappear for days before causing fever, joint pains and signs of vasculitis.

• Arrange admission - urgent ambulance (999).
• Give benzylpenicillin whilst waiting for the ambulance unless history of immediate penicillin allergy after previous penicillin administration (e.g. difficulty in breathing, collapse, generalised itchy rash). Benzyl penicillin dose 1200 mg for adults, 600 mg if aged 1-9 years, 300 mg if <1 year.^3,8
• Cefotaxime may be used as alternative.
• Antibiotic should be injected intravenously or intramuscularly in adults and intramuscularly in children. The recommended site of intramuscular injection is the quadriceps muscle.¹
• Warn close family contacts that chemoprophylaxis may be required if meningococcal disease is confirmed (see below).

Meningococci are fastidious and samples require careful handling. Close liaison with microbiologist required.

• Blood culture x3.
• Blood for PCR (polymerase chain reaction); is increasingly used for diagnosis, serogrouping and multilocus sequence typing.¹
• Serum for serology - initial paired sample (second 2-6 weeks later).
• Pharyngeal swab (per-nasal if patient unable to cooperate) other swabs as appropriate, stool for virology. State "meningococci?" on form.
• Lumbar puncture - once patient is stable, and an assessment made to rule out raised intracranial pressure (may need CT scan). Send cerebrospinal fluid for microscopy, culture, glucose, PCR.
• Aspirate from other sterile sites suspected of being infected (e.g. joints) for microscopy, culture, PCR.
• Full blood count, electrolytes, renal function tests, liver function tests.
• 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).

Hospital management¹

• Antibiotics:
  • Do not delay treatment in acutely ill patients - start antibiotics and supportive therapy as soon as possible (may require ITU) and investigate afterwards.
  • Choice of antibiotics in hospital should be guided by local protocols but the following are usually used:
  • Benzylpenicillin, cefotaxime, ceftriaxone, and chloramphenicol are effective antibiotics.
  • Patients are usually initially given cefotaxime or ceftriaxone, often combined with vancomycin until the causative agent has been identified.
  • When N. meningitidis is identified, antibiotic treatment should be continued with benzylpenicillin alone or a third-generation cephalosporin.
  • Traditionally are treated for 7 days, but 3 or 4 days of intravenous treatment have proved to be curative.
  • Chemoprophylaxis (see below) is sometimes recommended for patients given penicillin or chloramphenicol for treatment as pharyngeal carriage may not be eliminated with these antibiotics.
• Aggressive management of raised intracranial pressure reduces mortality.
• Fluid treatment with colloids and crystalloids, usually combined with vasopressor therapy including dopamine, noradrenalin, adrenalin or dobutamine. Aggressive fluid treatment is often required but requires very careful monitoring and care as excessive volume treatment may cause fatal brain oedema and herniation.
• Most patients with fulminant meningococcal sepsis require dialysis; haemofiltration has been used to reduce oedema.
• Anticoagulants are frequently given for patients with disseminated intravascular coagulation but has not been shown to improve outcome.
• Adults with septic shock and impaired adrenal function benefit from low doses of steroids but this benefit has not been shown in children. There is no evidence that dexamethasone reduces death from cerebral oedema or deafness in patients with meningococcal meningitis.

• 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's 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.
• Amputations and abnormal bone growth due to necrosis have been increasingly seen recently as a result of meningococcal disease.²
• Septic complications: septic arthritis, purulent pericarditis, endophthalmitis, pneumonia.
• Immune-complex complications, e.g. 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%), cutaneous vasculitis.

• Mortality is now about 10%. 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

This should be offered as soon as possible after case is confirmed:³

• To close contacts of cases, irrespective of vaccination status, e.g. those who have had prolonged close contact with the case in a household type setting during the seven days before onset of illness (i.e. 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 contraindicated if jaundice is present or previous sensitivity):
  • Adults and children >12 years - 600 mg orally twice daily for 2 days.
  • Children aged 1-12 years - 10 mg/kg dose orally twice daily for 2 days.
  • Children aged <1 year - 5 mg/kg orally twice daily for 2 days.
• Rifampicin can be used in pregnancy (although caution is advised and ceftriaxone is preferred). The dose for ceftriaxone is 250 mg IM/IV for an adult or 125 mg for a child<12 yrs.
• Ciprofloxacin is a useful when large numbers of contacts need prophylaxis - and can be used aged 5 (single dose of 500 mg orally if aged >12, 250 mg if aged 5-12).
• If serotype of case is identified as type A or C, contacts should also have subsequent meningococcal vaccine in addition to immediate chemoprophylaxis.

• 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).⁹ Also given with pneumococcal, HIB, and influenza vaccines for asplenic patients.
• Vaccines are available against group A and C serotypes for patients travelling to Africa and the Middle East.
• Pilgrims going to the Hajj and Umra require vaccine against groups A, C, W135 and Y.⁵
• Antibiotic prophylaxis in close contacts of index cases with rifampicin or ciprofloxacin (see above).