PENTINGNYA KELENGKAPAN DOSIS IMUNISASI DPT POLIO UNTUKPERLINDUNGAN JANGKA PANJANG

Asri purwanti

CVNama Lengkap : dr. Asri Purwanti SpA(K), MPd Tempat/Tanggal Lahir : Yogyakarta, 06-11-1955 Riwayat PendidikanDokter Umum (S1) : FK Universitas Diponegoro Semarang Tahun 1982 Dokter

Umum Dokter Spesialis (S2) 1994 Magister Pendidikan dan Konseling UNNES Tahun 2002Konsulen Kolegium Kesehatan Anak Indonesia / Pediatric Endocrinologi

Konsultan (S2) Tahun 2007 Program S3 in stem cell research in Down syndrome  Pendidikan Tambahan : 1995 : Pendidikan Lanjutan Klinik di Klinik Tumbuh Kembang Khusus dan

Genetika Klinis (dismorfologi) RSAB Harapan Kita Tempat di Jakarta 1996 : Kursus Genetika Klinis NUH Singapore Tempat di Singapore2005 : Orientasi di Sub Bidang Endokrinologi Anak FKUI Tempat di Jakarta2005 : Felloship APPES Pediatric Endocrinologi Tempat di Wuhan, Cina  

DPT POLIO MUNCUL LAGI..

BESARAN MASALAH PD3I DAN PERKIRAAN PENCAPAIAN CAKUPAN IMUNISASI DI

INDONESIA TAHUN 2010 (WHO-UNICEF)

No. of reported cases 2009 2008 2007 2006 2005

Msalah infeksi diphteri

BESARAN MASALAH PENYAKITDISTRIBUSI KLB DIPHTERI DI JATIM TH 2000 –

2012

KASUS DIFTERI DI JAWA BARAT 2001

Gambar 2. Persentasi Subjek dengan Titer Protektif Optimal ( > 0,1 )

19.316.8

5.27.8 7.8

0

36.8

30

20

24.3

17.5

5.1

25

1512.8

0

5

10

15

20

25

30

35

40

<1 1_2 2_3 3_4 4_5 5_6 SD I SD II SD III SD IV SD V SD VI SMP 1 SMP 2 SMP 3

Umur dan Kelas Sekolah

Tite

r Pro

tekt

if O

ptim

al >

0,1

DOSIS PENGUAT/ BOOSTER IMUNISASI DASAR

Survei imunitas difteri di Eropa: – Kadar antibodi rendah pada anak usia sekolah di negara

yang tidak melaksanakan dosis penguat pada usia prasekolah Mis: Swedia: imunisasi pada usia 3,5,12 bulan dan 1 kali dosis penguat di usia 10 tahun

* Seroprotection: antitoxin concentrations ≥0.1 IU/ml**ESEN: European Sero-Epidemiology Network*** Children who received primed at 2,4,6 months showed even lower seroprotection rates and were removed

PELAKSANAAN DOSIS PENGUAT IMUNISASI DASAR DI EROPA Use of a ‘full’

diphtheria toxoid dose for preschool booster is the standard in Europe

EU.VACNET. National Childhood Vaccination Schedules; available at: http://www.euvac.net/graphics/euvac/vaccination/vaccination.html

Countries using full diphtheria toxoid dose (D)Countries using reduced diphtheria dose (d)

JADWAL DOSIS PENGUAT DPT DI EROPA

Masalah pertusis

KASUS PERTUSIS DI INDONESIA, 2006

Fasilitas Kesehatan

Jumlah kasus

Puskesmas1 7,185

RS-rawat jalan1 252

RS-rawat inap1 144

Laporan WHO2 3,356

1. Depkes. Indonesian Health Profile 2006 : 422. WHO. Incidence Series 2010

Kasus pertusis terutama pada anak-anak dan dewasa muda

Umur (tahun) 1

Jumlah kasus1

< 1 640

1-4 1,840

5-14 2,060

15-44 1,692

> 45 1,349

Total 7,581

N0 TAHUN

GOLONGAN UMUR

<1 TH 1-4 TH 5-14 TH

15-44 TH

>45 TH

JML

1 2005 25 38 29 31 34 157

2 2006 18 33 2 8 23 79

3 2007 26 62 14 29 37 168

4 2008 19 47 53 24 23 172

DISTRIBUSI KASUS PERTUSIS MENURUT GOL.UMUR DI JAWA TIMUR TAHUN 2005 – 2008 (JULI)

Separuh pada usia yg perlu dosis penguat

PEMBERITAAN ANGKA KEJADIAN PERTUSIS MENINGKAT DI AS

KASUS PERTUSIS DI AS

Perlindungan yang diberikan oleh vaksinasi berkurang dengan bertambahnya waku:

Vaksin wholeP: 4-12 tahun Vaksin acellullar P: 6 tahun

Belum adanya petanda imunitas serologi yang pasti untuk memperkirakan lamanya imunitas yang dimiliki.

~2 years following infection or vaccination, antibodies barely reach detectable levels

HOWEVER, immunity to infection remains

Wendelboe et al. PIDJ, 2005

Rationale for Pertussis Preschool Booster

Immunity to Pertussis is not Lifelong

Infants younger than 1 year are the most vulnerable: 81% of cases related hospitalizations occurred before 4 months

(Australia, 2001 national active surveillance) >90% of pertussis-related deaths among infants <12 months

(USA, 2000-2004: 92%) Susceptibility in this age group is due to:

Fewer transplacental transfer of maternal antibodies due to waning immunity in adults

No vaccination before 2 months of age in most primary schedules

Protection probably not optimal until some time after completion of primary series

Reduction of exposure to B. pertussis is the only way to protect vulnerable infants too young to be (fully) vaccinated

Elliott et al. Pediatr Infect Dis J 2004CDC. WER, 2006Hewlett. NEJM, 2005Beard & Finn. J Public Health Med, 2000

Rationale for Pertussis Preschool Booster

Infants are Particularly Vulnerable to Pertussis-Related Complications

Netherlands, 1998-2005 analysis and comparison pertussis cases registered in the national notification system, hospital registry, and death registry between 1998-2001 (without preschool booster) and 2002-2005 (with preschool booster).

Preschool booster introduced in November 2001 * Both 1-4 and 5-9 age groups contain children eligible for the preschool booster Adapted from de Greef et al. PIDJ, 2008

Rationale for Pertussis Preschool Booster

Preschool Booster Provides both Protection to Preschool Children and Herd Immunity to Susceptible Infants

0-5 mo 1-4 yr* 5-9 yr*

6-11 mo 10-19 yr 20-59 yr 60+ yr

%

80

60

40

20

0

-20

-40

-60Age groups

Changes in incidence of hospitalizations and notifications after preschool pertussis booster introduction

(from 1998-2001 to 2002-05) Hospitalizations

Notifications

40%48%

32%

20%

44%

15%

0-5 mo 1-4 yr* 5-9 yr*

6-11 mo 10-19 yr 20-59 yr 60+ yr

%

80

60

40

20

0

-20

-40

-60Age groups

Changes in incidence of hospitalizations and notifications after preschool pertussis booster introduction

(from 1998-2001 to 2002-05) Hospitalizations

Notifications

Hospitalizations

Notifications

40%48%

32%

20%

44%

15%

Strong decrease of pertussis burden in the targeted cohorts*:

An estimated 79% effectiveness of booster vaccine

40% decrease of hospitalization incidence among infants 0-6 months (from 222.5 to 133.6/100,000)

UK cost-effective study of booster vaccination at 4 years of age, over a 5 year period and assuming herd immunity between 35-100% and willingness to pay 110,000 £ per LYG* reported positive public health impact (21b) : 50% of simulations were cost-effective from Health Care Provider’s

perspective 75% of simulations were cost-effective from Societal perspective In addition, >20% of simulations are cost-saving fro Societal perspective

Results based on a dynamic model of pertussis transmission, and presented in terms of herd immunity levels (given high uncertainty of this parameter). Underreporting was also taken into consideration

Positive public health impact demonstrated in a study in the Netherlands: After inclusion of preschool booster in 2001, strong reduction in

hospitalizations 48% reduction among children aged 1-4 years 40% reduction among children aged 0-6 months

* Life Year Gained de Greef et al. PIDJ, 2008

Edmunds et al. Vaccine, 2002 Postma et al. Vaccine, 2009

Rationale for Pertussis Preschool Booster

Preschool Booster Provides Positive Public Health Impact; Potentially Cost-Effective and Cost-Saving

PERLUNYA PROTEKSI TERHADAP BAYI RENTAN

Penelitian CDC, AS: – 774 kasus bayi di 4 negara bagian dari tahun 1999-2002 – Wawancara orang tua dari 616 kasus bayi, dapat

diidentifikasi 264 sumber penularan

Bisgard et al. PIDJ, 2004

PERLUNYA DOSIS PENGUAT Cakupan imunisasi 100% pada bayi dan anak,

masih memungkinkan adanya risiko penularan pertusis kelompok bayi rentan.

Kelompok bayi rentan tertular pertusis: Berkurangnya imunitas terhadap pertusis pada

usia dewasa, berisiko transfer antibodi transplasental pada ibu berkurang

Ada interval waktu tidak dapat diberikan imunisasi, pada: Bayi umur kurang dari 2 bulan Bayi karena suatu hal, tidak dapat tepat waktu

melengkapi jadwal imunisasinya.Infants Mencegah penularan pada bayi rentan,

dianjurkan memberikan dosis penguat imunisasi pertusis pada: Anak prasekolah (4-6 tahun) Remaja Dewasa

Forsyth et al. CID, 2004 Forsyth et al. Vaccine, 2007

PERLUNYA PROTEKSI TERHADAP BAYI RENTAN

•Angka kejadian pertusis yang harus dirawat 51,4% terjadi karena penularan diantara anak yang tinggal serumah•Risiko terjadinya pertusis yang harus dirawat pada bayi, meningkat bila tinggal serumah dengan anak usia sekolah (4,19 kali lebih tinggi)

Hviid et al. Vaccine, 2006

EXPERTS ACKNOWLEDGE NEED FOR PERTUSSIS PRESCHOOL BOOSTER

“It is universally acknowledged that even if 100% coverage in infants and children was achieved, infants too young to be [fully] vaccinated would still be vulnerable”

“All countries should consider expanding existing vaccination strategies to include pertussis booster doses in preschool children (4-6 years), to adolescents, and in those specific adults that have the highest risk of transmitting B. pertussis infection to vulnerable infants”

Strategy recommendations of the Global Pertussis Initiative

Forsyth et al. CID, 2004 Forsyth et al. Vaccine, 2007

Masalah infeksi tetanus

A Childhood tetanus immunization schedule of 5 doses is recommended. Primary series of 3 doses of DTP3 should be given in infancy (age<1year), with a booster dose of tetanus toxoid-containing vaccine ideally at age 4-7 years and another booster in adolescence, at age 12-15years)

Yet, as vaccination programs are based on combined vaccines (DTP at least), need and timing of booster doses are driven by the weaker immunogens, i.e. pertussis and diphtheria

European Centre for Disease Prevention and Control. ECDC Guidance. Scientific panel on childhood immunization schedule: Diphtheria-tetanus-pertussis (DTP) vaccination. 2009.

Rationale for Tetanus Preschool Booster

CIRCULATING VACCINE-DERIVED POLIOVIRUS OUTBREAKS (CVDPVS), 2000-2011

Type 2 (478 cases)

Type 1 (79 cases)

Type 3 (9 cases)

A preschool IPV booster is necessary to maintain long-term immunity against polioviruses

IPV is needed in both pre- and post-polio eradication era In the pre-eradication era:

Avoid paralytic polio cases associated with Oral Poliovirus Vaccine (OPV) use (in the form of vaccine-associated paralytic polio [VAPP] or vaccine-derive poliovirus [VDPV])

Eliminate remaining wild-poliovirus and circulating VDPVs (cVDPVs)

In the post-eradication era Maintain a world free of polio given potential for

reappearance of poliovirus and risk of bioterrorism

WHO Position Paper. WER, 2006

Rationale for Poliovirus Preschool BoosterEnsure High Protection Against both Wild Type and Vaccine Derived Polio

Safety and Immunogenicity of the Preschool Booster with TETRAXIM®

Safety and Immunogenicity of the Preschool Booster with TETRAXIM®

TETRAXIM®TETRAXIM®

• 1st licensed in 1998 • Licensed in >80 countries • ~15 million doses distributed to date

Licensed under the trade name TETRAVAC® in the European Union

Sanofi Pasteur. Internal data 2010

Countries where TETRAXIM® is licensed

Sanofi Pasteur. TETRAXIM® PPI. Data on file Edwards & Decker. In: Vaccines, 5th ed., 2008

Vidor & Plotkin. Hum Vaccin, 2008Carlsson & Gustafsson. 10-year report.

http://www.smittskyddsinstitutet.se/upload/SMI-rapport%20nr%204-2008.pdfWHO. WER, 2006WHO. WER, 2009

TETRAXIM®TETRAXIM®

Vaksin untuk tetanus, difteri, pertusis dan poliomyelitis: Tetanus toksoid : T ≥ 40 IU/dosis Diphtheria toksoid: D ≥ 30 IU/dosis 2 komponen Pertusis acellular†: PT* 25µg/dosis

FHA* 25µg/dosis†Reaktogenitas rendah, mengandung komponen Pertusis acellular †2-komponen aP memiliki imunogenitas dan efektif terhadap pertusis.

IPV††: Poliomyelitis virus (inactivated) Tipe 1 40 DU/dosis Poliomyelitis virus (inactivated) Tipe 2 8 DU/dosis Poliomyelitis virus (inactivated) Tipe 3 32 DU/dosis

††Disesuaikan dengan kebutuhan pra dan pasca eradikasi polio††Kandungan antigen (IMOVAX® Polio) = vaksin IPV pertama yang diterima

oleh prakualifikasi WHO

IMUNOGENISITAS VAKSIN

TETRAXIM® (n=219)

DTaP (Biken) + IMOVAX® Polio (n=223)

Historical reference:Pentaxim®, France for D,T,PT,FHA

IMOVAX® Polio, S. Korea for PV1,2,3

Seroprotection/Seroconversion rates following primary immunization at 2,4,6 months of age

0

20

40

60

80

100

D T PT FHA PV1 PV2 PV3

Sero

prot

ectio

n or

Sero

conv

ersi

on ra

tes

(%)

≥0.01 IU/ml ≥0.1 IU/ml ≥4x rise (EU/ml) ≥8 (1/dil)

92.4 92.5

78.4

Methodology: Open, two-arm, multicenter, randomized, controlled, phase III trial in 442 infants:Group A (n=219): 3 doses of TETRAXIM® vaccine at 2,4 and 6months of ageGroup B (n=223): 3 doses of commercially available separate DTaP and IPV vaccines at 2,4 and 6months of age.

Immunogenicity of TETRAXIM® administered as Preschool booster in children aged 5-6 years (after primary series and 1st booster with Pentaxim®/Pentavac®*) (n=69) Strong anamnestic

response observed 1 month after preschool booster with TETRAXIM®

* Pentaxim®/Pentavac®: DTacP-IPV-Hib at 2-4 or 2-6 and 12-16 months

Mallet et al. Vaccine, 2004

Proportion of children exhibiting a 4-fold rise in Ab titers following booster

dose with TETRAXIM®

0

20

40

60

80

100

D T PT FHA PV1 PV2 PV3

Prop

ortio

n with

4-fol

dris

e of A

b tite

rs (%

)

99.6 100 98

79

9593

93

TETRAXIM® Induces overall Anamnestic Response when Administered to Preschool-Aged Children

% of children with antibody levels after the 1st and before the 2nd booster doses

KIPI LOKAL

Solicited local reactions followingany dose of vaccine

3336,9

2722,1

15,68,8

0

20

40

60

80

100

Tenderness Erythema Swelling

% o

f do

ses

follo

wed

by

reac

tion

s

Methodology: Open, two-arm, multicenter, randomized, controlled, phase III trial in 442 infants:Group A (n=219): 3 doses of TETRAXIM® vaccine at 2,4 and 6months of ageGroup B (n=223): 3 doses of commercially available separate DTaP and IPV vaccines at 2,4 and 6months of age.

KIPI SISTEMIK

Methodology: Open, two-arm, multicenter, randomized, controlled, phase III trial in 442 infants:Group A (n=219): 3 doses of TETRAXIM® vaccine at 2,4 and 6months of ageGroup B (n=223): 3 doses of commercially available separate DTaP and IPV vaccines at 2,4 and 6months of age.

KIPI DOSIS PENGUAT PRA-SEKOLAH

TERIMA KASIH

 Diphtheria

toxin extracted from

C. diphtheriae culture

 Tetanus toxin

extracted from

C. tetani culture

 Pertactin, PT, FHA and

Fimbriae (AGG 2+3) extracted

from B. pertussis culture

 Poliovirus types 1, 2

and 3 propagated

on Vero cells

 PRP

capsular polysaccharide extracted

from H. influenzae

type b culture

Detoxification(formaldehyde**/

heat)Purification

Detoxification(formaldehyde**/

heat)Purification

PurificationSimple detoxification

of PT(glutaraldehyde)* and chemical treatment of

FHA

PurificationInactivation

(formaldehyde** + heat)

Purification, activation

and conjugation with concentrated

tetanus protein 

Adsorption onto Aluminium hydroxide

Blending

Purified diphtheria

toxoid

Purified tetanus toxoid

Adsorbed, purified Pertactin, PT, FHA and Fimbriae (AGG

2+3)

Concentrated trivalent

polioviruses

PRP conjugated to tetanus protein

BlendingAddition of adjuvant and buffers

Filling of sterile syringes

PEDIACEL™

Manufacture of PEDIACEL™