Meningococcal Disease

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Meningococcal Disease

• Alistair McGregor

Chair Bruce King
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The Meningococcus

• Neisseria meningitidis
• Alistair McGregor
• Royal Hobart Hospital

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Mr S.D.

• 21 yo male
• Previously fit well
• No regular medications
• Professional guitarist

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Mr S.D.

• Presented to Gp with 16 hour Hx
• Flu-like illness
• Febrile, nauseated
• Lethargy
• Generalized aches (muscular)
• Feels terrible

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Mr S.D.

• O/E
• Temp 375
• Reddened pharynx
• Coryza
• Dx viral illness
• Rx Amoxil, Panadene

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Mr S. D.

• Worked that evening ( Saturday )
• Felt worse
• Presented to DEM 2200
• Triaged - 3 hour wait
• Leaves to attend party

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Mr S. D.

• Brought back to DEM by partner 0200
• Worsening symptoms
• Headache
• Nausea
• Generalized muscle aches

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Mr S.D.

• O/E
• Temp 38
• Pale
• Smells of alcohol
• Drowsy, agitated
• Uncooperative with exam

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Mr S.D.

• Investigations
• FBC normal WCC and differential
• CRP 45
• U E normal
• CXR NAD
• CT Head NAD

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• CSF
• 2 red cells, 35 polymorphs, 8 lymphocytes
• Glucose 2.3 ( 2.7 - 5.1 )
• Protein 5.2 ( 1.5 - 0.45 )
• Gram stain negative

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Progress

• Dx Meningo-encephalitis
• Empiric therapy
• Ceftriaxone
• Penicillin
• Acyclovir
• No steroids

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Progress

• Sudden deterioration
• Hypotension
• Peripheral shutdown
• Decreased consciousness
• Developed petechial rash
• Episode of haematemesis

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Review by Intensivist

• Hypotensive (70/-), tachycardic (140)
• Bilateral conjunctival haemorrhages
• Extensive rash, rapidly spreading
• Poor peripheral circulation, peripheral cyanosis

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Progress

• Sedated, paralysed, intubated, ventilated
• Central vascular access
• Volume resuscitation
• Crystalloid 5000ml, Platelets 6 units,FFP 4
  units, Cryoprecipitate
• Antithrombin III 2000u
• Heparin 5000u stat, then 10 000u q24h

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Mr S. D. - contd.

• Partner very worried
• 2 year old child from previous relationship
• Bar owner rings next morning
• wants advice

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Meanwhile - back in the lab .

• CSF - no growth
• Blood cultures - no growth
• Throat swab - N meningitidis untypable
• PCR ( blood ) - Positive for N meningo. Sent away
  for typing

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Progress

• Multiple returns to OT for
• Further debridement of necrotic skin both legs
• Change of dressings, Colostomy formation
• Skin grafting
• Debridement of necrotic muscle compartments R leg
• Detipping fingers (L) hand
• Amputation R below knee
• Amputation L below knee

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Outcome

• Lost
• 4 fingers (PIP) on left
• 2 lower legs
• sacral skin (Grafted Day 56)
• Gained
• Fluid
• Colostomy
• Neuropathic pain

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Outcome - contd.

• Discharge
• from ICU DAY 30
• (_at_2,000/day 60,000)
• from hospital day 68
• (_at_500/day 34,000)

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This Is Very Bad !

• What can we do ?
• understand pathogenesis
• understand epidemiology
• diagnose early
• clinical
• laboratory
• optimize therapy
• prevention / public health measures

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Neisseria Meningitidis

• Gram negative coccus
• Fastidious
• Polysaccharide capsule
• virulence factor
• typing
• Normal flora of human URT

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N. meningitidis serogroups

• gt13 serogroups based on capsular polysaccharides
• Commonest serogroups
• A, B, C, W-135 and Y
• 3 major serogroups cause different patterns of
  disease

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Carrier Status

• 5 to 10 population asymptomatic carriers
• may be transient, intermittent or chronic
• asymptomatic carriage more common in
  adolescents and young adults and less in young
  children
• vast majority with nasopharyngeal carriage do
  not develop disease

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Pathogenesis

• Colonisation v Invasion
• Organism factors
• virulence
• Host factors
• immunity (local, complement)
• integrity of URT epithelium
• Disease when meningococci cross epithelial
  barriers, multiply in blood and disseminate
• Disease more likely if newly acquired or if
  acquired from patient with disease

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Transmission

• Primary mode of transmission is by
• CLOSE CONTACT (Aerosol )
• large droplets lt 3ft (1m)
• person to person contact with respiratory
  secretions

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Pathogenesis - contd.
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Endotoxin
Anti-cytokine substances e.g..soluble
receptors (cytokines,endotoxin), glucocorticoids
Monocyte Macrophage
Cytokines
Induce iNOS
TNF,IL-1
Activate Cascades Complement Kinin Coagulation
Nitric Oxide
Phospholipid derivatives PAF,PGs,IL-B4
?VO2
?SVRI
Myocardial depression
Chemotaxis
Increased permeability
SIRS/MODS/Shock
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Epidemiology

• International
• Australian
• Local

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Serogroup differences

• A epidemics/pandemics with high attack rates
• Meningitis belt of Africa
• Australia - 1942, 1987
• New Zealand - late 1980s
• B sporadic cases or outbreaks with low attack
  rate (Aus. mortality 6.4)
• epidemic in New Zealand since 1990
• C sporadic cases or outbreaks with moderate
  attack rates (Aus. mortality 14.9)

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In Australia

• Endemic infections with cyclical peaks
• Seasonal peak in winter-spring
• Bimodal age distribution
• 0-4 years and 15-25 years
• Slight male preponderance
• Overall notification rates 1.7-2.7 per 100,000

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Prevalence (Australia)

• 1986 lt 1 per 100,000 population
• 1991 1.9 per 100,000 population
• 1997 2.7 per 100,000 population

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N. meningitidis isolates, 1999 by serogroup
(Australia)
(n 369 isolates)
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Meningococcal strain differentiation data

• Serogroup B has predominated in most States since
  1994
• Serogroup C strains are increasing particularly
  in NSW and VIC

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Age-specific distribution (Australia)
Natural immunity develops during childhood - by
age 20 years 80 of persons have adequate immunity
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At Risk Groups

• Most cases sporadic but localised clusters may
  occur amongst
• Household members
• Child care centres
• Education facilities
• Those who have shared saliva with case
• Those exposed to a case after onset of symptoms
• Usually annual winter/spring peak.
• Rates are increased by smoking, exposure to
  smoke or URTI

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Infectivity of cases

• Most cases acquire infection within 7 days
  prior to onset
• Cases themselves are not efficient
  transmitters but remain potentially infectious
  till organisms are cleared from nose throat
  (24 hours after ABs)

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Invasive Meningococcal Disease in Tasmania
1990-2001
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Diagnosis - Clinical

• Septicaemia alone 15 - 20 do worse
• Useful clues
• rash, rigors, myalgia, vomiting
• rapid progression
• parental / partner concern
• age
• High index of suspicion
• Yung McDonald MJA Feb 2003

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Diagnosis - Laboratory

• Full Blood Count
• Left Shift
• Leucocytosis
• Abnormal Coags ?
• Elevated CRP
• Procalcitonin

• Microbiology
• Gram stain
• Culture
• PCR
• Serology
• (Antigen Test)

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Treatment

• Definite or suspected cases
• Benzylpenicillin or (amoxy)ampicillin
• - exquisitively sensitive
• - does not remove nasopharyngeal carriage
• Cefotaxine or Ceftriaxone
• - removes nasopharyngeal carriage lt 24hrs
• Supportive therapy
• With appropriate antibiotic therapy lt 10
  fatality rates

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Contact Tracing and Prophylaxis

• Notification Criteria
• Isolation of Neisseria meningitidis from a
  normally sterile site or skin lesion OR
• Detection of gram negative intracellular
  diplococci in blood or CSF OR
• Detection of meningo. antigen or nucleic acid in
  joints, blood, CSF, tissue or urine

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Who should notify Public Health?

• Attending medical/nursing clinician
• When? On suspicion
• URGENT Phone / Fax PHU
• Pathology Labs
• When? On confirmation
• URGENT Phone / Fax PHU

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Who does what?

• Public Health Unit Action
• liaise with attending clinician / RN
• interview family / case
• prescribe organise free chemoprophylaxis
• provide accurate information

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1 - Defining close contacts

• Household members e.g..
• anyone staying under the same roof
• Other very close contacts e.g..
• close travelling companions
• Kissing contacts, sexual partners
• Same-room contacts at child-care facilities
• but usually NOT school / institution / work
  contacts
• Low risk to health care staff - they use Standard
  Precautions!!

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Nosocomial Transmission

• Rare but can occur
• Study in England Wales 15 year period
• - 3 HCWs acquired meningococcal disease
• - gt 30 minutes with primary case around
• time of admission
• - direct exposure to respiratory droplets
• (had not worn masks or taken prophylactic
• antibiotics)
• RHH 15 years - NO nosocomial transmission

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Infection Control Issues

• Respiratory Isolation (gown, gloves, mask) 24
  hours
• Meningococci undetectable after 24 hours
  treatment
• If transfer lt 24 hours patient to wear mask
• Not known as environmental contaminant (not
  able to be isolated from environmental surfaces
  or samples)

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2 - Chemoprophylaxis

• Rifampicin
• reduces nasopharyngeal carriage by 80 - 90
  within 1 week of treatment
• taken orally BUT
• doesnt prevent recolonisation or disease if
  incubating
• overuse encourages AB resistance

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Alternatives

• Rifampicin is not for all
• ? Pregnancy
• ? Active liver disease
• ? Hypersensitivity
• Alternatives
• Ceftriaxone - IM (ok during pregnancy)
• Ciprofloxacin - oral

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3 - Maintaining calm

• Who is affected
• healthcare staff
• immediate extended family
• friends and associates
• neighbours
• schools / childcare
• general community
• the media

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Vaccination

• Now 2 types of vaccine
• 1. Polysaccharide (Mencevax / Menomune)
• cover against groups A,C,W135, Y
• short term
• 2. Group C Conjugated polysaccharide (Meningitec
  / Menjugate / NeisVac-C)
• - against group C ONLY
• - long lasting
• NB No Group B Vaccine as yet

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Polysaccharide vaccines

• induce antibodies in 10-14 days in 90 if gt 2yo
• single dose but boosters after 3 years
• about 39 per dose
• fails to reduce carriage rates
• does NOT protect against group B
• overseas travelers to endemic areas
• Tasmanian State access scheme since June 02 for
  13-30yo.

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Conjugate Meningococcal vaccines

• Gp C polysaccharide conjugated to carrier protein
  (like Hib)
• Effective in infants (but 3 doses needed if lt 1
  yo)
• Long-lasting protection likely
• Group C is on the increase (2/3 of cases in Tas
  recently). Excellent results in UK program
• C/wealth program 1/1/03 now routine at 1yo
• Catch up being rolled out for all 1 19 yos
  over next three years.

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MenC catch up program

• Phased over 4 years
• Start Up 2003 1st part
• 1 Jan 2003 1 4y 11m via GPs
• 15-19 yo via school programs only
• Catch up 1 July 2003 onwards
• 6 14 yo also via school programs only
• 15 19 yo continues
• Mop Up 2005 - 2006

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Public Education and awareness
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8th
..mid/late 2003?
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Invasive Meningococcal Disease in Tasmania
1990-2001
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Adult Meningococcal Disease in Tasmania 1990-2000

• Southern Region 10 cases
• Northern Region 12 cases
• Northwest Region 3 cases
• (25 Adult infections, 94 Paediatric infections)

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Meningococcal serogroups in Tasmania 1998-2001
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Deaths due to Meningococcal Disease in Tasmania
1990-2001
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Greater Hobart Area - 2001

• 17 confirmed cases
• Incidence rate (per 100,000)
• 2001 (12/12) 8.75 (total population), 38.74
  (15-24 yrs)
• Sept-Nov 2001 (3/12) 7.21 (total population),
  31.70 (15-24 yrs)
• Additional probable cases

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Greater Hobart Area - 2001
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Clinical cases

• 17 confirmed cases
• Hyperacute clinical presentation
• Bacteraemia with/without meningitis
• 4 deaths (mortality 23.5)
• 11 males, 6 females
• Ages ranged 2-60 yrs (average age 24.4 yrs)

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Confirmed cases

• All had blood cultures taken 11/17 BC ()
• of the 6 patients with BC (-)
• 2 EDTA PCR () and IgM ()
• 2 EDTA PCR (-) and IgM ()
• Only 2 patients had CSF taken (both children)
• 1 CSF culture () and blood culture (-) (CSF and
  blood PCR ())
• 1 gram negative diplococci (CSF culture (-) and
  blood culture and PCR (-))

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Confirmed cases

• 12/17 had PCR performed on EDTA blood 9/12 ()
• 8/17 had IgM performed 7/8 IgM () (1 negative
  result was on sera taken on day 1)
• No single diagnostic test is perfect
• Clinical suspicion remains extremely important

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Outbreak strain

• Serogroup C
• PorA VR type P1.5,2
• PorB VR type C,Eb,2a,C

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Early 2002

• Tasmania - 9 confirmed cases till May
• 7 in Greater Hobart ( cf 1 in 2001 )
• 1 death ( plus SA case - not included )
• 6 serogroup C
• ? drift in age group effected ?
• Hobart - since 6/5/02
• 2 confirmed, 2 ( 3 ) possible cases

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Local Action

• Task force
• ID/Micro, Public Health, Health Policy makers
• Interstate assistance sought
• Modeling performed
• 10 / 100,000 in 3 months
• at risk group
• vaccine costs and availability

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Modelling 10 / 100, 000 in 3 months

• Total of 20 proven cases in Southern Tas
• approx 1 every 4 days
• expect
• up to 10 further probable cases
• 3 - 4 deaths
• 3 - 4 permanently disabled

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Outcome

• Defacto vaccination campaign
• October 2001 gt 10,000 doses of Meningitec
• State Govt.. campaign June 2002 - ongoing
• Polysaccharide vaccine
• economically vulnerable target group ( N 30,000
  )

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Subsequently

• Federal Govt. campaign Early 2003 - ongoing
• Conjugate C vaccine to all infants
• catch up campaign for teenagers
• Hobart
• no type C since June 2002