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Country Spotlights: IsraelCountry Spotlights: Israel
Prof. David Greenberg M.D.Prof. David Greenberg M.D.
The Pediatric Infectious Disease UnitThe Pediatric Infectious Disease UnitSoroka University Medical CenterSoroka University Medical Center
BenBen--Gurion UniversityGurion UniversityBeerBeer--Sheva, IsraelSheva, Israel
OutlineOutline
Epidemiology• Invasive pneumococcal disease (IPD)
• Pneumonia
• Acute otitis media (AOM)
• Antibiotic resistance
Vaccine serotypes coverage• Invasive pneumococcal disease (IPD)
• Acute otitis media (AOM)
• Antibiotic resistance
• Ethnic differences in southern Israel
Israel DemographyIsrael Demography
• Total population: 7,116,700 (2006)
• Jewish population: 80% (5,703,400)
• Arab population (Mainly Muslims and Christians): 19.8% (1,413,300)
• 28% (2,017,800) younger than 14 years
Distribution of the Main Pathogens Causing CommunityDistribution of the Main Pathogens Causing Community--Acquired Acquired Bacteremia in children <5 years Southern Israel, 1992Bacteremia in children <5 years Southern Israel, 1992--2001 2001
Gur E, Frank M, Givon-Lavi N, Peled N, Press J, Dagan R, Leibovitz E. Scand J Infect Dis. 2006;38(8):604-12.
30
42
57
9
00
8
13
711
3
0
5
10
15
20
25
30
35
40
45
1m-12m 13m-60m
S. pneumoniae S. aureus H. influenzae type b Brucella spp Salmonella spp E. coli
% o
f all
path
ogen
s
Incidence of Invasive Infections (Hospital Figures) in Southern Incidence of Invasive Infections (Hospital Figures) in Southern Israel, Age < 2 yrs: Israel, Age < 2 yrs: S. S. pneumoniaepneumoniae ((PncPnc) vs. ) vs. H. H. influenzaeinfluenzae b b
((HibHib) and ) and N. N. meningitidismeningitidis ((MncMnc))
* Pediatric Infectious Diseases Soroka University Medical Center
0
25
50
75
100
125
150
175
200
89 90 91 92 93 94 95 96 97 98 99 00 01 02 03 04 05 06
Inci
denc
e/10
0,00
0
Inc Mnc
Inc Pnc
Inc HiB
2
52
188
55559914
26
57
104
0
20
40
60
80
100
120
1 2 3 4 5 6 7 8 9 10-13 14-16 17-35 36-55 56-65 ≥66
Inci
den
ce/1
00,0
00/y
rIn
cide
nce
/100
,000
/yr
Age (years)Age (years)
Incidence of Invasive Pneumococcal Disease in IsraelIncidence of Invasive Pneumococcal Disease in Israel
Dagan et al, JAMA 268: 3328Dagan et al, JAMA 268: 3328--32, 199232, 1992Raz R, et al. Clin Infect Dis. 1997; 24:1164Raz R, et al. Clin Infect Dis. 1997; 24:1164--88
8
4
7
8 8
9
0
5
10
0 to 2 3 to 4 5 to 6 7 to 8 9 to 10 11 to 12
26 24
149
7
0
10
20
30
0-11 12-23 24-35 36-47 48-59
Yea
rly
inci
den
ce p
er
Yea
rly
inci
den
ce p
er
1,0
00
ch
ildre
n1
,00
0 c
hild
ren
Age (months)
Incidence of Hospital Use (ER Visits and hospitalization) for Incidence of Hospital Use (ER Visits and hospitalization) for Alveolar PneumoniaAlveolar Pneumonia in Children in Southern Israelin Children in Southern Israel
8% of all children will visit will visit the hospital because of the hospital because of
alveolar pneumonia during alveolar pneumonia during their 1their 1stst 5 years of life5 years of life
and 50% will be hospitalizedand 50% will be hospitalized
Annual Burden of Annual Burden of S. S. pneumoniaepneumoniae Disease in IsraelDisease in Israel
• ~350 invasive infectionsinvasive infections cases and 10 deaths
• ~10,000 ER visits for community acquired pneumoniacommunity acquired pneumonia
and 5,000 admissions
• ~50,000 acute acute otitisotitis mediamedia cases
• Non-susceptible to ≥ 1 antibiotic classes - 64%
• Non-susceptible ≥ 3 antibiotic classes (MDR) - 15%
• Penicillin Non-susceptible* - 35%
• Erythromycin resistance - 10%
Antibiotic NonAntibiotic Non--Susceptible Susceptible S. S. pneumoniaepneumoniae Isolates Isolates from Pediatric from Pediatric Invasive InfectionsInvasive Infections--
Israel (n=437)Israel (n=437)
Greenberg et al, J Clin Microbiol,41: 5541–5545, 2003
*MIC ≥ 0.1µg/ml
S. S. pneumoniaepneumoniae Antibiotic NonAntibiotic Non--Susceptible Rates in Susceptible Rates in Acute Otitis Media -- Southern Israel 1992 Southern Israel 1992 -- 20032003
Dagan et al. Pediatr Infect Dis J. 19:S58-65, 2000; Dagan, unpublished
136 10
1
41
22
50
2215
62
01020304050607080
Pen* TMP/SMX ERY R≥2 R≥3
Antibiotics
% o
f all
isol
ates
1992 (n=51) 1993 (n=100) 1994 (n=100) 1998 (n=563) 1999 (n=718)2000 (n=700) 2001 (n=672) 2002 (n=639) 2003 (n=740)
N = 4,283N = 4,283
*MIC ≥ 0.1µg/ml
OutlineOutline
Epidemiology
• Invasive pneumococcal disease (IPD)
• Pneumonia
• Acute otitis media (AOM)
• Antibiotic resistance
Vaccine serotypes coverage• Invasive pneumococcal disease (IPD)
• Acute otitis media (AOM)
• Antibiotic resistance
• Ethnic differences in southern Israel
Proportion and Incidence of invasive infectionsinvasive infections Caused by PCV-7 Vaccine-Serogroup S. pneumoniae (VT + Related) in Children Aged < 2 Yrs: Comparison Between Southern Israel and W. Europe
Pro
port
ion
of
all I
PD
cau
sed
by
vacc
ine
sero
grou
ps
Jefferson et al, Lancet Infect Dis, 6:405-1, 2006Dagan and The Israeli Pediatric Bacteremia and Meningitis Group, unpublished dataHausdorff et al, Lancet Infect Dis; 5: 83-93, 2005
70% 72%47%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
W. Europe Israel Jewishchildren
IsraelBedouinchildren
Incidence 28 65 240(/100,000)
Inci
den
ce o
f IP
D c
ause
d by
vac
cin
e se
rogr
oups
per
10
0,0
00
0
20
40
60
80
100
120
W. Europe Israeli Jewish children
Israeli Bedouin children
20
47
113
Slide prepared by Ron Dagan MD
20
30
40
50
60
70
80
90
7VT 10VT 13VTVaccines (VT=valent)
% C
umul
ativ
e
+ 6A
The potential coverage of the pneumococcal vaccines in The potential coverage of the pneumococcal vaccines in invasive infectionsinvasive infections in children <13 years (n=4009)in children <13 years (n=4009)
Dan Engelhard1, Ron Dagan2, Noga Givon-Lavi2 (for the Israeli Pediatric Bacteremia & Meningitis Group)- ICAAC 2005
Ethnic differences in the potential coverage of Ethnic differences in the potential coverage of different different PCVsPCVs in children in children < 3 years old< 3 years old in in Southern Israel with Southern Israel with invasive infectionsinvasive infections
93
7063
5280
7076
41
0102030405060708090
100
4 6B 9V 14 18C 19F 23F 1 5 7F 6A 3 19A
Jewish children (n=56) Bedouin children (n=133)
Serotype
% o
f all
isol
ates
PCV13PCV7 PCV10 + 6A
34 4147
6165
53
10092104
132
0
20
40
60
80
100
120
140
4 6B 9V 14 18C 19F 23F 1 5 7F 6A 3 19A otherts
Jewish children (n=56) Bedouin children (n=133)
Ethnic differences in Ethnic differences in invasive infectionsinvasive infections incidence incidence rates by the different rates by the different PCVsPCVs in children < 3 years in children < 3 years
old in Southern Israelold in Southern Israel
Cum
ulat
ive
inci
denc
e/10
0,00
0
PCV7 PCV10 PCV13+ 6A
Serotype
Ethnic differences in the potential coverage of Ethnic differences in the potential coverage of different different PCVsPCVs in children < 3 years old in in children < 3 years old in
Southern Israel with Southern Israel with acute acute otitisotitis mediamedia
857164
60 75
5662
49
0102030405060708090
100
4 6B 9V 14 18C 19F 23F 1 5 7F 6A 3 19A
Jewish children (n=1,294) Bedouin children (n=1,903)
Serotype
% o
f all
isol
ates
PCV7 PCV10 PCV13+6A
Comparison of serotype coverage by the various Comparison of serotype coverage by the various PCVPCV’’ssin in invasive infectionsinvasive infections caused by caused by antibiotic nonantibiotic non--
susceptible susceptible S. S. pneumoniaepneumoniae
Pen-intermediate Pen-R Ery-R MDR
PCV-13PCV-10 (+6A) PCV-10 (+6A)PCV-7 PCV-7 (+6A)
0
10
20
30
40
50
60
70
80
90
100
% o
f all
isol
ates
MIC 0.1-1µg/ml MIC > 1µg/ml
Current situation of the PCVCurrent situation of the PCV--7 in Israel7 in Israel
Date1/06 7/06 1/087/07
MoH advisory Committee for infectious diseases and immunizations recommended to include PCV-7 in NIP 2009
1/07
PCV-7 Registration in Israel
All Israeli professional medical organizations recommend PCV-7
The Israeli MoH recommend PCV-7 to all children with reimbursement for selected high risk children
National symposium PCV-7 held by the professional medical societies
MoH announced a 4-years plan for new vaccines and for the PCV-7 to be planned in NIP 2009
All health insurance organizations started to subsidize PCV-7
2nd PCV symposium Planned by the Israeli medical societies
• Streptococcus pneumoniae is a major cause of invasive infection
and mucosal diseases in children in Israel
• Antibiotic resistance rates and MDR are high
• PCV-7 serotypes coverage is moderate, however because of the
high disease incidence in the country its potential in disease
reduction is significant
• The future investigational PCV-10 and PCV-13 have higher
coverage rates than PCV-7 and can potentially reduce the burden
of invasive and mucosal diseases in Israel
• The Israeli MoH future plans are to expand the national
immunization program and to include the PCV-7 in 2009
Summary
2030405060708090
<6 6-23 24-59 ≥60
%7VT
10VT
13VT
2030405060708090
<6 6-23 24-59 ≥60
%
The potential coverage of Pneumococcal vaccines of serotypes The potential coverage of Pneumococcal vaccines of serotypes causing causing invasive infectionsinvasive infections in Israeli children, in different age in Israeli children, in different age
groups in Jewish and nongroups in Jewish and non--Jewish childrenJewish children
Jews Non-Jews
Age (months)Dan Engelhard1, Ron Dagan2, Noga Givon-Lavi2 (for the Israeli Pediatric Bacteremia & Meningitis Group)- ICAAC 2005
Age (months)
% o
f all
Pnc
isol
ates