Estimating the impact of meningococcal
group C conjugate vaccine on hospitalization
for invasive disease in Italy, 2001-2011
Domenico Martinelli
Sector of Hygiene, Department of Medical and Surgical
Sciences, University of Foggia, Italy
Puglia Regional Observatory for Epidemiology, Italy
ESCAIDE – Stockholm, 5-7 November 2014
Domenico Martinelli
2
Sector of Hygiene, University of Foggia, Italy
Background
Meningococcal C vaccination coverage (VC) in Italy and Puglia region by birth cohort
Data collection 2006-2013
90%
80%
70%
VC
60%
50%
40%
30%
20%
10%
13
13
16
16
18
18
0%
2004
2005
2006
2007
2008
Birth cohort
MenC VC, Italy [1]
2009
2010
2011
MenC VC, Puglia [2]
Number of Italian regions with available VC data [1]
[1] Average VC% in a pool of Italian Regions, CNESPS ISS. Dati e evidenze disponibili per l’introduzione della vaccinazione anti-meningococco B nei
nuovi nati e negli adolescenti. June 2014. [2] Apulian Immunization Registry (GIAVA Puglia).
Domenico Martinelli
3
Sector of Hygiene, University of Foggia, Italy
Background
Meningococcal C and ACYW135 VC in Puglia region by birth cohort
Data collection 2006-2013
80%
70%
60%
VC
50%
40%
30%
20%
10%
0%
1995
1996
1997
MenC VC, Puglia [1]
[1] Apulian Immunization Registry (GIAVA Puglia).
1998
1999
Birth cohort
2000
2001
MenACYW135 VC, Puglia [2]
2002
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
Rationale and Objective
Strong experience in
anti-meningococcal C
vaccination
Recent introduction of the
new meningococcal group
B vaccine (4CMenB) in the
immunization schedule of
some Italian regions
To assess the epidemiological burden
and pattern of Invasive
Meningococcal Disease (IMD)
4
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
Methods
 Assessment of IMD burden in Puglia region, 2001-2013
 Evaluation of the sensitivity of available data sources
 Capture-recapture analysis
 Comparison of Puglia region vs Italy
 Comparison between pre and post MenC vaccination era
 Incidence rate ratios (IRRs) and 95% CI, by Poisson regression
 Impact of anti-Men C vaccination program
 Attributable benefit, preventable fraction, prevented fraction
 Missed opportunities of mass vaccination programme
 Analysis of data collected through an ad hoc surveillance system
on suspected IMD cases aged 0-30 years
 Estimation of the 4CMenB vaccination potential impact
 Laboratory confirmed cases in the target population
5
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
Results
Evaluation of the sensitivity of data sources in identifying meningococcal meningitis
Puglia region 2001-2013
Hospital Discharge
Registry (SDO)[1]
Invasive Bacterial
Disease
Surveillance (MIB)[2]
Infectious Disease
Routine Notification
System (SIMI)[3]
Llinkage key: name, surname, date of birth
Meningococcal meningitis
cases
Evaluation of sensitivity*
Capture-recapture analysis [4]
*
• Univocal case definition: clinical features + laboratory confirmation
• Case has the same probability of being present in each data source
[1] HDR
regional archive. [2] Regional archive o Invasive Bacterial Disease Surveillance. [3] Regional archieve of the Infectious
Disease Routine Notification System. [4] Gallay A et al. How many foodborne outbreaks of Salmonella infection occurred in
France in 1995? Application of the capture-recapture method to three surveillance systems. Am J Epidemiol. 2000;152(2):171-7.
6
Domenico Martinelli
7
Sector of Hygiene, University of Foggia, Italy
Results
Evaluation of the sensitivity of data sources in identifying meningococcal meningits
Puglia region 2001-2013
Models
DoF
Gp2
p
AIC
BIC
x
N
95% CI
Indipendent (no interaction)
3
80.34
0
74.34
74.5
20
210
200-225
Interaction (MIB, SIMI)
4
25.75
0
21.75
21.86
56
246
222-283
Interaction (MIB, SDO)
4
78.31
0
74.31
74.41
24
214
202-233
Interaction (SIMI, SDO)
4
51.99
0
47.99
48.1
4
194
190-203
Interaction (MIB, SIMI) and (MIB, SDO)
5
2.33
0.13
.33
.39
270
460
303-932
Interaction (MIB, SDO) and (SIMI, SDO)
5
19.12
0
17.12
17.17
17
207
194-240
Interaction (MIB, SIMI) and (SIMI, SDO)
5
51.99
0
49.99
50.04
4
194
190-204
Satured: interaction (MIB, SIMI) and (MIB, SDO) and (SIMI, SDO)
6
0
1
0
0
116
306
215-691
Sensitivity
SDO
36% (95% CI: 16-51)
Sensitivity
MIB
34% (95% CI: 15-48)
Sensitivity
of the pool of cases
62% (95% CI: 27-88)
Sensitivity
SIMI
40% (95% CI: 18-57)
Domenico Martinelli
8
Sector of Hygiene, University of Foggia, Italy
Results
IMD incidence in Italy and Puglia region, 2001-2012
Incidence of hospitalization for IMD in Italy [1]
IMD incidence in Puglia - Cases from datalinkage SIMI (meningococcal meningitis), MIB (meningitis
and/or meningococcal septicemia), SDO (ICD9-CM: 036.x - meningococcal infection in all diagnosis)
0.8
Incidence (x100,000)
0.7
Puglia Region
IRR = 0.7 (0.4-1.4)
0.6
0.5
0.4
0.3
0.2
0.1
Men C
0
2001
2002
2003
2004
2005
2006
2007
Year
2008
2009
2010
2011
2012
[1] CNESPS ISS. Dati e evidenze disponibili per l’introduzione della vaccinazione anti-meningococco B nei nuovi nati e negli
adolescenti. June 2014.
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
Results
Impact of MenC universal routine vaccination (URV) in subjects aged <24 yrs
Puglia region, 2001-2013
Attributable benefit[1]
Incidence x100,000
IMD mean annual incidence before
and after MenC URV introduction
1.20
Reduction of the risk (in terms of incidence)
attributable to URV
1.00
Preventable fraction[1]
-0.4
Ple F =
0.80
0.60
I 2001-2013 - I 2006-2013
= 19.4%
I 2001-2013
Proportion of cases that theoretically could have
been prevented if URV had been introduced
since 2001
1.05
0.40
0.65
0.20
Prevented fraction[1]
Ped F =
0.00
2001-2005
2006-2013
Period
[1] Last
AR = I 2006-2013 - I 2001-2005 = -0.4 ´100, 000
I 2001-2005 - I 2001-2013
= 23%
I 2001-2005
Proportion of total cases presumably avoided
with the introduction of URV
MD. A Dictionary of Epidemiology. Forth Ed. Oxford University Press, Inc. New York (US): 2001.
9
Domenico Martinelli
10
Sector of Hygiene, University of Foggia, Italy
Results
Prevented fraction of IMD cases <24 yrs, by achieved MenC vaccination coverage
Puglia region, 2001-2013
RR =
Ped F = PResponders ´(1- RR)
[1]
I 2001-2005
= 0.61
I 2006-2013
PResponders = VC ´VE
45%
[2]
EV=100% [1]
Prevented Fraction
40%
EV=83%[1][2]
35%
30%
25%
PedF=23%
20%
15%
10%
5%
VC=57%[3]
0%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90% 100%
Vaccine coverage (%)
[1] Last
MD. A Dictionary of Epidemiology. Forth Ed. Oxford University Press, Inc. New York (US): 2001[2] RCP Menjugate®,
revisione luglio 2009. [3] CV media nelle coorti target dell’offerta vaccinale
Domenico Martinelli
11
Sector of Hygiene, University of Foggia, Italy
Results
Active surveillance of IMD cases aged ≤30 yrs
Puglia region, January 2013 – September 2014
11 cases of IMD recorded - 3 missed opportunities
Enrolment
date
Sex
Age
Serogrop
Sequelae
Exitus
Vaccines
administrated
Active call to
vaccination
June 2013
M
11
Y
Partial
deafness
No
None
February 2013
October 2013
F
13
Y
None
No
None
January 2011
May 2014
F
18
C
None
Yes
None
February 2007
Meningococcal conjugate vaccines history in Puglia region
January
2006
November
2011
May
2014
Men C at 15 months
Men C at 11-12 years
Men C at 15 months
Men ACYW135 at 11-12 years
4CMenB at 3, 4, 6, 15 months
Men C at 15 months
Men ACYW135 at 11-12 years
DGR 30/12/2005, n. 2037. Piano Regionale della Prevenzione 2005-2007. Approvazione del Piano regionale Vaccini triennio 2005-2007. BURP n. 12 del 24-1-2006.
Commissione Tecnico Scientifico Vaccini. Verbale n. 1/2011. 21 novembre 2011. DGR 20 maggio 2014, n. 958. Commissione Regionale Vaccini. Modifica Calendario
Regionale per la vita 2012 ‐ DGR 241/2013. Approvazione nuovo Calendario Vaccinale per la vita 2014. BURP n. 74 dell’11‐06‐2014
Domenico Martinelli
12
Sector of Hygiene, University of Foggia, Italy
Results
Estimation of the 4CMenB vaccination potential impact in Puglia region
IMD annual incidence before and after
MenC URV introduction
Serogroup distribution of N. meningitidis isolates
in Puglia region, 2006-2013 (N=16)
1.20
1.05
1.00
Incidence x100,000
W135
6%
A
6%
0.80
0.65
0.60
Y
19%
B
63%
0.40
C
6%
0.20
0.00
2001-2005
2006-2013
VE
87% (95%CI: 70%-93%)*
Period
* Vogel U et al. Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative
assessment. Lancet Infect Dis 2013;13(5):416-25
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
13
Limitations
 Limited number of IMD cases
 Even more than scarce number of cases routinely
typed in the past
Take home messages
 In Puglia, MenC universal vaccination is modifying the
burden of IMD
 IMD cases decrease in children and adolescent  Need to
improve and maintain high VC for a further reduction of
IMD due to Neisseria meningitides serogroup A, C, Y e
W135
 Remain IMD cases due to Neisseria group B  crucial role
of the extensive introduction of the new 4CMenB vaccine
Domenico Martinelli
Sector of Hygiene, University of Foggia, Italy
14
Acknowledgements
 Novartis Vaccines and Diagnostic s.r.l. to support the ad
hoc laboratory-confirmed surveillance with an
unrestricted grant
 CNESPS ISS for providing the analysis of the national
background
 Co-Authors: Cozza V, Cappelli MG, Fortunato F, Prato R
Thank you for your attention
domenico.martinelli@unifg.it