Control of Serogroup C Meningococcal DiseaseThe Quebec Experience
Philippe De Wals
Université Laval
Institut national de Santé publique
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MENINGOCOCCAL DISEASE IN CANADA
C-MD Outbreaks: 1991 – 1994
ABBC
QCMB
SK
ON
NBNS
NF
PEI
NUNYK
NWT
Increased incidence of C-MD since 1990
Spaciotemporal clustering
High incidence in adolescents
High fatality rate
Virulent C ET 15 clone
Epidemiologic Situation in Quebec
Fall 1991
Meningococcal Disease Cases
1990-1994
Serogroup B(n = 160)
Serogroup C(n= 292)
Sequelae 3% 15%
Case fatality 7% 14%
(Erickson et coll. 1998)
Thymo-Independant Immune Response to Polysachharide Vaccine
Polysaccharide Antibodies
Lympho. B Plasma Cell.
Bactericidal Antibodies One Month after MenC-PS-Vac
1
10
100
1000
0.5 y 1.0 y 1.5 y 2.0 y 5.0 y 11.0 y 15.0 y
Log GMT
Age
(King et al. J Pediatr 1996; 128: 196-202)
Persistence of Anti-C Antibodies in Children Vaccinated
Between 6 to 8 Years of Age
0123456789
10
GMT (ug/ml)
t 0 1 mo 1 yr 3 yr 4 yr
(Lepow et al. Pediatrics 1977, 60: 673-680)
Serogroup C PS Vaccine Trials
in Military RecruitsVaccine Efficacy 95% C. I.
Walter Reed(Artenstein et al. )
87% 57%-100%
Squibb(Gold et al.)
88% 52%-100%
Region Date Nb vaccines
Outaouais-Laurentide Jan 92 175 000
Sud Lanaudière Jan 92 48 000
Roberval Fév 92 3 000
Valleyfield Avr 92 11 000
Lakeshore Avr 92 4 000
FermontAvr 92 1 000
Châteauguay Mai 92 10 000
Nord Lanaudière Oct 92 33 000
Cluster Immunization 1992-1993
Decreased incidence in vaccinated groups
New outbreaks and sporadic cases in unvaccinated groups
Epidemiologic Situation Fall 1992
MASS VACCINATION December 92- March 93
• Target : Population aged 6 mo to 20 yr
• Vacciness : Bivalent PS & Tetravalent PS
• Doses administered : 1 625 000
• Coeverage : 84%
• Average vaccine purchase price = 5.26 $
Vaccination Coverage
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6 mois 20 ans
%
(De Wals et coll. Bull WHO 1996, 74: 2840-4)
Average = 84%
Costs of Campaign (x 1000 $)
Vaccine purchase 10 586 $
Vaccine distribution 445 $
Vaccine administration 12 174 $
Communication-promotion 242 $
Medical services 2 848 $
Vaccine registry 125 $
Care adverse reactions 39 $
Evaluation 100 $
Total 26 417 $
(Direction de la santé publique, 1994; Buteau et coll. 1998)
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0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20Age in years
VE
%
Efficacy of Men-C-Vac According to Age
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VACCINATED
NOT VACCINATED
CUM RATE / 100 000
YEAR AFTER VACCINE ADMINISTRATION0
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VACCINATED
NON VACCINATED
Rate / 100 000
Years after vaccine administration
Cumulative Incidence C-MD 1993-1998(De Wals et coll. JAMA 2001, 285:177-81)
Effectiveness of Mass Campaign
Directprotection
Directprotection &
herdimmunity
Cases averted 48 74
Deaths averted 7 11
(De Wals et coll. Vaccine 2002, 20:2840-4)
Cost-Effectiveness of Mass Campaign
Directprotection
Directprotection
& Herdimmunity
Cost/Death averted $ 3.0 M $ 1.7 M
Cost/ LY gained $ 105 000 $ 58 000
Coût /QALY gained $ 87 000 $ 49 000
(De Wals et coll. Vaccine 2002, 20:2840-4)
Conjugate Meningococal Vaccines
MCC-CRM197 (Chiron Vaccines – Menjugate)
– 10 g serogroup C oligosaccharide conjugated with CRM197 protein (AlOH3)
MCC-TT (Baxter {NAVA} – Neis Vac)– 10 g serogroup C polysaccharide (de-O-acetylated)
conjugated with tetanus toxoid ( AlOH3)
MCC-CRM197 (Wyeth Lederle Vaccines - Meningitec)
– 10 g serogroup C oligosaccharide conjugated with CRM197 protein (AlPO4)
Thymo-Dépendent Immune Response to Conjugate Vaccine
Antibodies
Plasma Cell. Polysaccharide
B Lympho.
Proteine
T Lympho.
Memory Cell.
SBA GMTs in UK infants after 3 doses of MCC at 2/3/4 months and challenge with 10 ug plain C polysaccharide
at 4 yrs of age.
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e-1st
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2nd
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3rd
6 mon
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3yrs
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Post
chall
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SBA
GMT
SBA responses to MCC vaccines & 10 ug plain polysaccharide booster 6 months later in UK toddlers
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SBAGMT
PostMCC
Pre-boost
Post-boost
Pre-MCC
50ug * Polysacc.
naïve toddlers
MCC Vaccine Efficacy Estimates in the UK
Subjects No. of Doses VE (95% CI)
Infants Exactly 3 91.5% (64.9 - 98.0)
Infants 2 or 3 88.6% (58.4 - 96.9)
Infants Any 79.7% (38.2 - 93.3)
Toddlers 1 89.3% (72.7 - 95.8)
Pre-School* 1 100% (84.9 - 100)
Years 1-11** 1 95.3% (88.3 - 98.6)
Years 12/13*** 1 91.9% (73.3-98.4)
* Pre-school = 3/4 yrs ** Year 1 to 11 = 4/5 yrs to 14/15 yrs
*** Year 12/13 = 15 to 17 yrs
Increased incidence February 2001
Spatiotemporal clustering
Adolescents
High fatality and sequelae rate
Virulent C 2a p1.1,7 ET15 Clone
Epidemiologic Situation
Spring 2001
Number of Articles in Newspapers
January - September 2001
• La Presse 68
• Le Devoir 26
• Le Soleil 91
Predicted Costs and Effectiveness of Mass Campaign
C-PS & C-Con
C-Con
Vaccine purchase 73 771 93 454
Administration 16 317 16 317
Total ($ x 1000) 90 088 109 771
Cases averted 187 210
Deaths averted 26 29
MASS CAMPAIGN SPRING-FALL 2001
• No vaccinated : 48 000 MenC-PS & 1 804 000 MenC-Con
• Coverage : 84%
• Few adverse reactions
• Decreased incidence
• Two documented vaccine failures
Usefulness of Mass Immunization Campaign
0,0%
5,0%
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25,0%
30,0%
35,0%
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45,0%
50,0%
Tout à faitd’accord
Plutôt d’accord Plutôt endésaccord
Tout à fait endésaccord
Ne sais pas
Economic Evaluation of Routine Children Immunization
• 25 birth cohorts
• 75 000 births/yr
• Follow-up Age 25 yr
• Study period 2002-2050
• $ 50 per dose
• Discounting = 3%/yr
Epidemiologic Scenarios Relative Probabilities
1) Endemicity 0.03
2) 1 epidemic 0.15
3) 2 epidemics 0.23
4) 3 epidemics 0.28
5) 4 epidemics 0.18
6) 5 epidemics 0.08
7) Hyperendemicity 0.02
Immunization Strategies
• Do nothing
• Routine 3 doses ( 2, 4 et à 6 mo)
• Routine 1 dose (1 yr)
• Mass campaign
Health System Program Costs
Vaccinepurchase
Administration Total
Mass 70.0 M$ 19.9 M$ 90.0 M$
1 Dose 87.7 M$ 8.4 M$ 96.1 M$
3 Dose 263.2 M$ 25.1 M$ 288.4 M$
C-MD Incidence (1 outbreak)
2002
2005
2008
2011
2014
2017
2020
2023
2026
2029
2032
2035
2038
2041
2044
2047
2050
aucune vaccination
vaccination de masse
routine 1 dose
routine 3 doses
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années
cas
Routine 3doses
Routine 1dose
MassVaccination
Endemicity 2 656$ 903$ -1 outbreak 956$ 267$ 302$2 outbreaks 904$ 255$ 447$3 outbreaks 596$ 121$ -4 outbreaks 486$ 102$ -5 outbreaks 389$ 68$ -Hyperendem. 62$ (52$) -
Societal Cost per C-MD Case Averted
(x 1 0000 $)
Incremental Cost-Effectiveness RatioScénario 2 éclosions/50 ans et taux d'actualisation = 3%/an
$1
$10
$100
$1 000
$10 000
$100 000
$1 000 000
$10 000 000
$100 000 000
$1 000 000 000
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Cas Evités
Co
ût
466 007
-198 7177 731 811
1 458 880
Do nothing
Vaccination de masse
Routine 1 dose
Routine3 doses
Average* Cost-Effectiveness RatioOne-Dose Strategy
Cost per LY gained = 23 000 $
Cost per QALY gained = 39 000 $
*Weighted-average of probabilities of 7 scenarios
Meningococcal Programs in Canada
• Alberta : 3 doses (after mass campaign)
• Quebec : 1 dose (after masss campaign)
• British Columbia : 1 dose (& catch-up)