MENINGOCOCCAL DISEASE IN THE UK CHALLANGES STILL TO BE FACED

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• MENINGOCOCCAL DISEASE IN THE UK CHALLANGES
  STILL TO BE FACED
• Professor Keith Cartwright
• Public Health Laboratory
• Gloucester Royal Hospital

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Introduction of MCC vaccinesUK, November 1999

• decision based on detailed epidemiology
• burden of men C disease well documented
• serological correlates of protection assumed
• ambitious but achievable programme
• evidence of protection to be generated
• Men B disease will continue

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Confirmed group C meningococcal infectionsWeeks
27-51, 1999 and 2000
Age group (years)
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MCC vaccines for the UKstatus in December 2000

• over 18 million doses distributed
• no concerns regarding supplies
• good coverage in schools (but lower in older
  children)
• poor coverage in pre-school toddlers
• adverse events publicity requiring DH response

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Bacterial meningitis in the UK

• meningococcus (serogroups B C)
• pneumococcus
• Heamophilus influenzae type b (Hib)
• Tubercular
• others

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Bacterial meningitis in the UKWhere are we now?

• Hib eliminated in 1990s
• reduction of 1,200 cases per annum
• Meningitis case fatality rate falling
• Men C down by 80 by 2001
• reduction of 1000 cases per annum
• BUT disease persists in unimmunised young adults
• Men B incidence rising (2000 cases p.a.)

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H. influenzae type b infections by quarter
England Wales, 1990 - 1994
Conjugated vaccines introduced
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Meningococcal disease, England
Walesmortality, 1970-1997
Case fatality ratio expressed as
deaths/notifications rolling 3 year average
1970
1990
1980
Year
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Incidence of men C disease, England Wales weeks
1-26, 1998 - 2000
Nos of cases
1998
2000
1999
Year (weeks 1 - 26)
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Estimated incidence of bacterial meningitis
meningococcal disease in the UK, 1999
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Estimated incidence of bacterial meningitis
meningococcal disease in the UK, end 2001
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Men B disease is the challenge
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What is meningococcal disease?
Neisseria meningitidis
3 serogroups - A, B, C
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What is meningococcal disease?
Neisseria meningitidis
3 serogroups - A, B, C

• may invade to cause
• meningitis (85)
• septicaemia (15)

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Meningococcal disease, England Walesannual
numbers of notifications
Numbers of notifications
Meningitis
Septicaemia
1970
1980
2000
1990
Year
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Meningococcal diseaseage-specific incidence
Incidence per 105
Months
Years
Age
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Meningococcal diseasethe UK strategy
Short term minimise morbidity mortality
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Meningococcal diseaseoptimising current
management
Rapid transfer to hospital
Intensive inpatient management
Early recognition antibiotic treatment
New immunomodulators
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Meningococcal diseaseoptimising current
management
Rapid transfer to hospital
Intensive inpatient management
Early recognition antibiotic treatment
New immunomodulators
Reduction in mortality of gt 70
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Meningococcal diseasethe UK strategy
Short term minimise morbidity mortality
Medium term disease elimination
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Meningococcal disease prospects for vaccines

• Serogroup A C
• conjugated vaccines now available (1999 - 2000)
• - safe immunogenic
• - will give lifelong protection

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Meningococcal disease prospects for vaccines

• Serogroup A C
• conjugated vaccines now available (1999 - 2000)
• - safe immunogenic
• - will give lifelong protection

• Serogroup B
• many experimental approaches
• prospects good, but vaccines unlikely for 5-8 y

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Men B vaccines grounds for optimism

• No second attacks
• Very little disease in adults
• natural immunity is the norm
• 1st generation vaccines show promise
• Several candidate subcapsular antigens
• Men B genome sequenced

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Men B vaccines the different approaches

• Capsular
• Native polysaccharide complexed to OMV
• Conjugated, modified B polysacharide
• Subcapsular
• OMV vaccines (Cuba, Norway, RIVM recombinant
  porA)
• Several antigens (TBPs, nspA, Opa, lipoproteins
  etc)
• Men B genome sequencing project
• Live attenuated vaccines
• N. meningitidis, N. lactamica

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Men B vaccines stages of development
Basic research
Pre-clinical development
Manufacture for trials
Clinical trials
Licensure
OMV (Norway/Cuba)
OMV 2nd generation
Tbps A B
Tbp B
NspA
PorA peptide
Conjugated B PS
Live attenuated
N. lactamica
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Is there a front-running candidate men B
vaccine for the UK?

• No clear favourite as yet
• Genome sequencing candidates look promising
• Men B vaccines evolutionary not revolutionary
• Successful vaccines likely to be complex
• Need for regular reformulation is a possibility

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Why dont we use outer membrane vesicle vaccines
in the UK right now?

• OMV vaccines manufactured by Cuba Norway
• Both have production quality control problems
• 50-70 efficacy against homologous strains
• Some cross-protection in adolescents
• Ineffective in infants
• Men B strains in UK highly heterogeneous

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What are the priorities now?

• More work on reducing meningitis case fatality
  rates
• Continue intensive case ascertainment (all
  meningitis)
• Reduce men C disease in adults
• Clinical trials of pneumococcal conjugates
• Development clinical trials of men B vaccines
• Better blood tests of immunity