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

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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

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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

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Efficacy of Men-C-Vac According to Age

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NOT VACCINATED

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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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SBA

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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

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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)

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aucune vaccination

vaccination de masse

routine 1 dose

routine 3 doses

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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

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-198 7177 731 811

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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)