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

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er

Yea

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er

1,0

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ildre

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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