Meningococcal Disease (Neisseria Meningiditis)

Neisseria Meningiditis is a gram-negative diplococcus. Meningococcal disease usually presents as septicaemia, meningitis, or both. Meningococcal disease may also present with arthritis, osteomyelitis, conjunctivitis, endophthalmitis and chronic meningococcaemia.¹

• It is a usually found in the mucous membrane of the nose and throat of humans² (no known animal reservoir) with carriage rates varying from 2% in the under fives to years to a peak of 25% in 15-19 year olds (in unimmunised populations).³
• Carriage rates are greater in smokers, overcrowded households, and military recruits - and asymptomatic nasopharyngeal carriage is transient and eventually resolves (can take years)!
• Infection is transmitted from person to person by droplets or secretions from the upper respiratory tract, and most likely source of infection of virulent strains would seem to be household members or close friends who are asymptomatic carriers.
• 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 9 of which 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.
• WHO estimates caused 171,000 deaths in 2000. UK rates of invasive disease are 2-6 per 100,000 with approximately 10% fatality.
• In developed world, 1-3/100,000 population/year, mainly group C (40%), the remainder mostly group B.
• Large scale epidemics can occur in the developing world, mainly sub-Saharan Africa, due mainly to group A, with a 11% case mortality rate.
• Most infections occur during winter and early spring.^2,4
• 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. Most cases in young children are sporadic although outbreaks do occur, especially in adolescents.⁴
• 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.
• Risk factors: Influenza A predisposes to infection, as does asplenia, and possibly complement deficiencies.

• The classic features of septicaemia are a non-blanching rash in a feverish, ill child.¹
• However a recent 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.
• More non-specific 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 therefore very important in early diagnosis and therefore earlier initiation of potentially life-saving treatment.⁵
• The same study divided the clinical features into (the stated percentages are the frequency of features occurring in the study population).

• In the very young in particular, 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.

• 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 1200mg for adults, 600mg if aged 1-9 years, 300mg if <1 year, ideally IV (or IM).^2,6
• Cefotaxime may be used as alternative.
• Warn close family contacts that chemoprophylaxis may be required if meningococcal disease is confirmed (see below).

• 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:
• Benzyl penicillin in very high doses.
• Cefotaxime or ceftriaxone plus vancomycin as blind treatment of bacterial meningitis.

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

• Blood culture x3.
• Blood for PCR (polymerase chain reaction).
• 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.

• Early complications - seizures, raised intracranial pressure, cerebral venous or sagittal sinus thrombosis, and hydrocephalus.
• In severe fulminant meningococcaemia - disseminated intravascular coagulation and adrenal failure (Waterhouse-Friderichsen's syndrome).
• 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.¹
• Septic complications: septic arthritis, purulent pericarditis, endophthalmitis, pneumonia.
• 5-8% of cases show persistent problems such as headache, tiredness, sleeplessness, poor concentration problems and irritability, arthritis (10%), cutaneous vasculitis.

• Septicaemia 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.¹

This should be offered as soon as possible after case is confirmed:²

• 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 - 600mg orally twice daily for 2 days.
  • Children aged 1-12 years - 10mg/kg dose orally twice daily for 2 days.
  • Children aged <1 year - 5mg/kg orally twice daily for 2 days.
• Rifampicin can be used in pregnancy (although caution is advised and ceftrizaxone is preferred). The dose for ceftrizaxone is 250mg IM/IV for an adult or 125mg 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 500mg orally if aged >12, 250mg 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).⁷ 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.⁴
• Antibiotic prophylaxis in close contacts of index cases with rifampicin or ciprofloxacin.