|
| |
Created by CD Gomersall
Updated on November 2006
by Thomas Li
Epidemiology
- at least 13 serogroups with most cases due to infection with A, B or C serogroups of Neisseria
meningitides.
- highest rates of disease amongst infants but this may be altered by the
introduction of vaccination. About 50% of cases occur in children under 4
years. Small increases in incidence in late teenage years and above age of
65 years.
Risk factors
- deficiency of antibody-dependent, complement mediated immune lysis
- functional or anatomical asplenia
- properdin deficiency
- deficiency of terminal complement components
- household contacts of patient with invasive meningococcal disease
- tobacco smoke
- upper respiratory tract infection (probably diminshes barrier properties
of respiratory mucosa)
Pathogenesis
- respiratory droplet spread and direct mucosal contact results in
colonization of upper respiratory tract
- small minority of patients who are colonized with virulent strains develop
invasive disease. Usually occurs 2-4 days after colonization.
- bacteria migrate across epithelium into submucosal tissue and capillaries
resulting in bacteraemia
- may be followed by meningeal invasion
- bacterial proliferation and inflammatory response may occur predominantly
in subarachnoid space causing meningitis or in circulation causing
meningococcaemia
Clinical syndromes
Invasive disease presents as:
- meningitis without shock
- shock without meningitis
- meningitis and shock
- meningococcaemia without shock or meningitis
- respiratory tract infection
- pneumonia
- epiglottitis
- otitis media
- focal infection
- conjunctivitis
- endophthalmitis
- septic arthritis
- Osteomyelitis
- urethritis
- purulent pericarditis
Septic shock without meningitis
Characterised by:
- persistent circulatory failure
- severe DIC leading to:
- thrombosis and extensive haemorrhage of skin
- thrombosis and gangrene of extremities
- impaired renal, adrenal and lung function
- very rapid deterioration over hours
Clinical features
Classical features are fever, non-blanching rash and a sick child
- fever
- diarrhoea common in first few hours
- non-blanching rash
- haemorrhagic skin lesions
- initially bluish petechiae (larger than in idiopathic
thrombocytopaenic purpura)
- rapidly increase in size and number
- if non-blanching rash is more than 2 mm in diameter in a sick febrile
child, meningococcal disease is highly likely
- all over body but often more pronounced and appear early on
extremities
- occasionally on mucous membranes
- up to 30% of children with meningococcal disease may have non-specific
maculopapular rash, but most will have non-blanching element
- shock
- initially high cardiac output, although extremities often cold and
cyanotic with poor capillary refill
- Tachycardia
- Widened central-peripheral temperature gradient
- later cardiac output falls
- oliguria
- hypotension is a late sign in children
- neck stiffness usually absent and Kernig's sign -ve. Many patients alert
at time of hospital admission
- consumptive coagulopathy associated with inhibition of fibrinolysis by
release of plasminogen activator inhibitor 1 from activated endothelial
cells and platelets
- thrombosis occurs particularly in the skin, kidneys, adrenals, muscles
and limbs. Reduced concentrations of antithrombin III and protein C
(natural inhibitors of coagulation).
- ± multiple organ failure
- ARDS
- renal failure
- rhabdomyolysis
Clinical course
Rapid deterioration is common and death often occurs within 48 hours
Investigations
- Full blood count: low WCC with marked left shift
- blood cultures usually +ve
- Blood for polymerase chain reaction for meningococci
- Aspirate, smear or punch biopsy may show meningococci
- metabolic acidosis
- raised creatinine and urea
- glucose may be high, low or normal
- hypokalaemia, hypomagnesaemia, hypocalcaemia
- slightly raised AST and ALT but normal GGT
- CPK rises after 1-3 days due to rhabdomyolysis
- platelets, fibrinogen low
- fibrinogen degradation products elevated
- lumbar puncture contraindicated because of coagulopathy
Differential diagnosis
Pericarditis
- may present with cardiac tamponade
- fever, nausea, epigastric pain
- blood cultures may be -ve
Treatment
- immediate aggressive resuscitation with urgent transfer to the Intensive
Care Unit
- intravenous fluid 20 ml/kg and repeated if necessary
- high dose ceftriaxone (4g daily) or cefotaxime (2g 6hourly) in countries
with a significant risk of penicillin resistant N. meningitidis.
- high dose benzylpenicillin (2.4g 6 hourly) if penicillin resistance is not
a concern
- the following have been recommended but there are no controlled data
demonstrating an improvement in outcome:
- heparin (10-15 IU/kg/h)
- antithrombin III (to keep plasma concentration >35-40 IU/ml)
- protein C (loading dose 100 IU/kg followed by 15 IU/kg/h to keep
plasma concentration between 0.8-1.2 IU/ml)
- recombinant tissue plasminogen activator
- 0.25-0.5 mg/kg over 1.5-4 h
- to overcome inhibition of fibrinolysis
- if used, should be started early
- plasma exchange
Secondary prophylaxis
Should be offered to household and kissing contacts of patient
- rifampicin is not recommended for pregnant women. Patients taking oral
contraceptives should be warned to use alternative methods while rifampicin
is being taken. Patients should also be warned that rifampicin colours all
secretions and may stain soft contact lenses
- ciprofloxacin is not recommended for pregnant or lactating women. Should
not be used for prophylaxis in children unless no acceptable alternative is
available
- ceftriaxone, but not benzylpenicillin, eliminates nasal carriage of
meningococci. Patients who have not received ceftriaxone should be treated
with rifampicin to eliminate nasal carriage prior to discharge from hospital
Prophylaxis for healthcare workers
- Healthcare workers coming within 3 feet of patients should wear surgical
masks
- Eye protection should be worn when there is a risk of secretions
splashing onto face or into eyes
- Chemoprophylaxis should be offered to healthcare workers whose mouth or
nose is directly exposed to respiratory droplets/secretions within a
distance of 3 ft from a probable or confirmed case of meningococcal disease
who has received <24h appropriate treatment
- eg staff undertaking airway management during resuscitation without
wearing a mask or other mechanical protection or a clear perception of
physical contact with droplets/secretions
- Chemoprophylaxis is not recommended in the absence of a clear
history of exposure. General medical or nursing care of cases is not an
indication for prophylaxis
- Exposure of eyes to respiratory droplets is not an indication for
chemoprophylaxis but is associated with a low risk of conjunctivitis and
subsequent invasive disease. Staff should be counseled about this risk
and advised to seek early treatment if conjunctivitis develops within 10
days of exposure
| Drug |
Dose |
| |
Children |
Adults |
| Rifampicin |
<1 month: 5mg/kg 12hrly for 2 days
Others: 10mg/kg 12hrly for 2 days |
600 mg 12 hrly for 2 days |
| Ciprofloxacin |
Not recommended <18 years |
500 mg single dose |
| Ceftriaxone |
<15 years: 125mg IM single dose
Others: adult dose |
250 mg single dose |
Outcome
- Most children survive
- 8% die from septic shock and complications
- Among survivors
- 10% have neurodevelopmental consequences like cerebral palsy
- 10% have deafness
Further reading
Brandzaeg P. Meningococcal infections. In Warrell DA, Cox TM,
Firth JD, Benz EJ. Oxford Textbook of Medicine, 4th edition, 2003, Oxford,
Oxford University Press, pp 7.11.5
Rosenstein NE et al. Medical Progress: Meningococcal disease.
N Engl J Med, 2001; 344(18):1378-1388
Stuart JM et al. Preventing secondary meningococcal disease in health care
workers: recommendations of a working group of the PHLS Meningococcus Forum.
Communicable Disease and Public Health, 2001; 4:102-5
Hart CA and
Thomson APJ. Meningococcal disease and its management in children. BMJ 2006;
333: 685-690 |
