DAFTAR RIWAYAT HIDUP

1. IDENTITAS :
a. Nama : Dr. Eddy Fadlyana, dr., Sp.A(K), M.Kes
b. Unit Kerja – : Dept. Ilmu Kesehatan Anak FKUP/RSHS
b. Jabatan
– : Kepala Divisi Tumbuh Kembang–Pediatri Sosial
b. Alamat Kantor
– : Jl. Pasteur No.38 Bandung

2. RIWAYAT PENDIDIKAN
a. S1 :
b. Spesialis I FK. UNPAD Bulan Desember Tahun 1985
c. Spesialis II : FK. UNPAD Bulan MeiTahun 1996
d. S2 : Kolegium IDAI Bulan Juni Tahun 2002
e. S3 : FK. UNPAD Bulan April Tahun 2003
: FK. UNPAD Tahun 2011

El Royale Hotel Bandung 3-4

 Evolving Vaccination Needs Against
Six Vaccine Preventable Disease

Eddy Fadlyana

Child Health Department, Faculty of Medicine, Universitas Padjadjaran

/ Dr.Hasan Sadikin Hospital, Bandung, Indonesia
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INTRODUCTION

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 IMMUNIZATION SCEDULE

BCG Birth
Hep B Birth – 24 hour
DTP-HB-Hib 2. 3. 4 month and 18 month
DT 6 to 7 years
Td 7 to 8 year, 8 to 9 years, 15 to 39 years
OPV 1, 2, 3, 4 month
IPV 4 month
Measles 9 , 24 month, and 7 years
MR 9, 18-24 month, and 7 years
HPV 11 year, 12 year (Jakarta Prov)
PCV 2, 3, 12 month(Mataram)
JE 10 month (Bali Province)
Indonesia Immunization schedule, 2018
– EPI lauched in 1977
– Hep B vaccine introduction in 1997
– DTP-Hep B vaccine introduced ini 2004
– Pentavalent vaccine introduced in four provinces
in 2013 and gradually expended to all provinces
by 2014•
– tOPV to bOPV switched on 04 April 2016•
– IPV vaccine launched in national routine
immunization programme from July2016.

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16x9 core template Insert your date / confidentiality text here 11
 (DTwP+HB+Hib) + OPV+IPV
(DTaP+HB-Hib+IPV) = DTaP hexavallent

16x9 core template Insert your date / confidentiality text here 12

Whole cell Pertussis Acelullar Pertussis

– It consisted of diphtheria and tetanus – It consisted of diphtheria and tetanus

toxoids and a cellular component toxoids and individual antigens of B.
i.e.inactivated cells of Bordetella pertussis i.e.pertussis toxin,
pertussis. pertactin, fimbriae, adenylate cyclase
etc.
– DTP vaccine, introduced in 1940s, has – The action of shift from whole cell
been considered as an efficacious pertussis vaccine to acellular vaccine
vaccine in reducing the burden of all was carried out in 1990s after reports of
three diseases against that it protects side effects associated with DTwP
vaccines.
– Schedule: 2, 3, 4 month – Schedule: 2, 4, 6 month
– .Immunogenicty >> – Immunogenicity <<
– Safety << – Safety >>
– Efficacy 94% (CI 95%, 88–97%; – Efficacy 74-97% (CI 95%, 81–87%;
p<0,0001 p<0,0001).
Sendy Tjahjowargo dkk: Perbandingan efektivitas dan keamanan vaksin pertusis aselular dan whole-cell. Sari Pediatri 2017;18:403-8
Fulton TR, Phadke VK, Orenstein WA, Hinman AR, Johnson WD, Omer SB. Protective effect of contemporary pertusis vaccines: a systematic review and meta-analysis. Clin Inf Dis
2016;62:1100-10.,
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Rusmil et al. BMC Pediatrics (2015) 15:219
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– PAIN

– REDNESS

– SWELLING

– INDURATION

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 Table 1. Vaccination schedule.

0─3 d of age 2 mo of age 3 mo of age 4 mo of age

Hepatitis B bOPV bOPV bOPV

(birth dose)
bOPV DTP-HB-Hib DTP-HB-Hib DTP-HB-Hib
(Pentabio®) (Pentabio®) (Pentabio®)
IPV

The subjects’ parents or representatives kept an observation card

(i.e. a diary) to assess and record information on local and systemic
reactions for 30 days
3. Results

Description Total
N included 150
Gender
Male, n (%) 82 (54.7)
Female, n (%) 68 (45.3)
Age (days)
Mean (SD) 0.57 (0.64)
Min; max 0; 3
Table S1.
Seroprotection to poliovirus types 1, 2 and 3 at pre-immunisation, at post-first dose and post-fourth
dose of the study vaccine (n = 143). Per Protocol Immunogenicity Population.
Neutralisation Titre (NT ≥ 8) Neutralisation Titre (NT < 8)
Description n (%) 95 % CI n (%) 95 % CI
Anti-P1:
Pre-dose (n = 143) 89 (62.2) 54.1–69.8 54 (37.8) 30.2–45.9
Post 1st dose (n = 143) 116 (81.1) 73.9–86.7 27 (18.0) 13.3–26.1
Post 4th dose (n = 143) 143 (100.0) 97.4–100.0 0 -
Anti-P2: 128 (89.5) 83.4–93.5 15 (10.5) 6.5–16.6
Pre-dose (n = 143) 69 (48.3) 40.2–56.4 74 (51.7) 43.6–59.8
Post 1st dose (n = 143) 131 (91.6) 85.9–95.1 12 (8.4) 4.9–14.1
Post 4th dose (n = 143)
Anti-P3: 74 (51.7) 43.6–59.8 69 (48.3) 40.2–56.4
Pre-dose (n = 143) 80 (55.9) 47.8–63.8 63 (44.1) 36.2–52.2
Post 1st dose (n = 143) 142 (99.3) 96.1–99.9 1 (0.7) 0.1–3.9
Post 4th dose (n = 143)
Table S2.
Seroconversion to poliovirus types 1, 2 and 3 at post-first dose and post-fourth dose of the study
vaccine.
Description % seroconversion
Anti-P1 (n = 54)
Post 1st dose (n = 143) 42 (77.8 %)
Post 4th dose (n = 143) 54 (100.0 %)
Anti-P2 (n = 15)
Post 1st dose (n = 143) 0 (0.0 %)
Post 4th dose (n = 143) 14 (93.3 %)
Anti-P3 (n = 69)
Post 1st dose (n = 143) 33 (47.8 %)
Post 4th dose (n = 143) 69 (100.0 %)
Fig. 2.Geometric mean titers (GMT) of anti-poliovirus types
1, 2, and 3 at pre- and post-vaccination.
Table S3
Geometric mean titres (GMTs) of anti-poliovirus types 1, 2 and 3 at
post-first and post-fourth dose of the study vaccine.

Description GMT anti-poliovirus (95% CI)

Anti-P1: (n = 143)
Pre-dose (n = 143) 9.67 (7.20–12.96)
Post 1st dose (n = 143) 78.20 (53.75–113.76)
Post 4th dose (n = 143) 1495.55 (1294.79–1727.83)
Anti-P2: (n = 143)
Pre-dose (n = 143) 28.83 (23.10–35.99)
Post 1st dose (n = 143) 4.73 (3.69 –6.06)
Post 4th dose (n = 143) 23.45 (20.02–27.45)
Anti-P3: (n = 143)
Pre-dose (n = 143) 4.85 (3.770–6.24)
Post 1st dose (n = 143) 13.15 (8.77–19.72)
Post 4th dose (n = 143) 846.45 (727.11–985.14)
Fig. 3. Percentage of subjects reported solicited systemic adverse events after each
vaccination. Occurrence of systemic adverse events after each vaccination were categorized
into three time points: H0 (30 min post-vaccination), H1-H3 (>30 min – 72 h post vaccination)
and >H3 (>72 h – 30 days post vaccination).
2 3 4 11 mo 4 yrs 9 yrs

DTaP DTaP DTaP TdaP

2 3 4 11 mo 4 yrs 9 yrs

DTwP DTaP DTaP TdaP

These immunological data corroborate epidemiological data showing that
DTaP-primed adolescents are less protected against clinical pertussis than
DTwP-primed children.
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What is DTaP(3) hexavalent vaccine?

DTaP(3) hexavalent vaccine a is a combination vaccine targeting

six diseases* in infants and toddlers

Diphtheria
Tetanus
Pertussis
Hib†
Poliomyelitis
Hepatitis B

Primary dose Booster dose

Helps to protect Administered as either a Can be used in children

against six potentially 3+1 or 2+1 primary and >6 weeks of age§
serious diseases booster schedule‡

*Containing active substances derived from diphtheria, tetanus, pertussis and Hib bacteria, HBV, and inactivated polioviruses 1, 2 and 3
†Hib is provided as a separate powder and must be reconstituted in the DTPa-HBV-IPV suspension before use
‡Schedule dependent on locally-applied/recommended schedule as per local licensing
§Safety and efficacy have not been established in children >36 months of age

DTPa, Diphtheria-tetanus-acellular pertussis; HBV; Hepatitis B virus; Hib, Hemophilus influenzae type b; IPV, Inactivated polio virus
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GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.;
DTaP(3) hexavalent vaccine : clinical development
program

Objectives of the DTaP(3) hexavalent vaccine Additional phase

pivotal trials IIIb/IV studies

Preterm infants11–13
primary schedule1‒4 booster schedule*5‒10
Additional schedules:
• Assess the immunogenicity, reactogenicity, immune EPI9, 2+114–17
persistence and safety profile of DTaP(3) hexavalent
vaccine given as a primary vaccination1–4 Co-administration
with other pediatric
• Assess the immunogenicity, reactogenicity, immune vaccines18,19
persistence and safety profile of DTaP(3) hexavalent
vaccine given as a booster vaccination5–10
Additional countries20–24

*Booster given during the second year of life

EPI, expanded program of immunization by World Health Organization 6–10–14 weeks of age
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1.Schmitt HJ. 2000; 2. Arístegui J. 2003; 3. Zepp F. 2004; 4. Bogaerts H. 2003; 5. Behre U. 2016; 6. Heininger U. 2007; 7.GSK. InHx03 - 2013N163277_00; 8.GSK. InHx04 - 2013N163281_00;
9.Gatchalian S. 2007; 10. Zinke M. 2010; 11. Omeñaca F. 2007; 12. Omeñaca F. 2018; 13. Omeñaca F. 2011; 14. Avdicová M. 2015; 15. Gabutti G. 2004; 16. Avdicová M. 2002; 17. Thollot F.
2014; 18. GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.; 19. Dolhain J. 2020; 20. Reinert P. 2008; 21. Kosalaraksa P. 2018; 22. Lalwani SK. 2017; 23. Quiambao B. 2012;
24. Romanenko Vl. 2020
High seroprotection/seropositivity rates for all antigens
after primary and booster vaccinations with a 3+1 schedule
Primary schedule: first 12 months of life Booster
Months Months Months EPI schedule† 2nd year of life
(weeks)
2 4 2 6 3 5 6 14

3 4 4 10
Seroprotection/
seropositivity*

≥96.4% ≥96.6% ≥96.8% ≥95.7% ≥98.4%

N=196 N=1,693 N=1,055 N=265 N=2,009

2 studies 6 studies 6 studies 1 study 12 studies

*Seroprotective thresholds: anti-diphtheria, ≥0.1 IU/mL; anti-tetanus, ≥0.1 IU/mL; anti-HBs, ≥10 mIU/mL; anti-polio, ≥1/8 dilution; anti-PRP, ≥0.15 g/mL; seropositivity thresholds:
pertussis antigens PT, FHA, PRN ≥5 EL.U/mL
†EPI schedule (at 6, 10, 14 weeks of age) may only be used if a dose of hepatitis B vaccine has been given at birth

EL.U, Enzyme-linked immunosorbent assay test unit; EPI, Expanded program of immunization; FHA, Filamentous hemagglutinin; HB, Hepatitis B surface antigen; IU, International
unit; PRN, Pertactin; PRP, Polyribosylribitol phosphate; PT, Pertussis toxoid
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GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.
Up to 7 years of immune persistence across vaccine
antigens* with a 3+1 schedule1–3

4–6 years old (N=203)1 7–9 years old (N=200)1

3, 4, 5 or 2, 3, 4 months + 12–23 months 3, 4, 5 months + 12–24 months

Diphtheria Tetanus Pertussis HBV Hib Polio

100
Patients with seroprotection/
seropositivity, % (95% CI)

80

60

40

20

0
Anti-diphtheria Anti-tetanus* Anti-PT* Anti-FHA Anti-PRN Anti-HBs Anti-PRP Anti-polio type1 Anti-polio type2 Anti-polio type3

4‒6 years old (N=174–198) 7‒9 years old† (N=51–193)

*Waning of PT and tetanus antibodies is countered by pre-school booster dose

†These data are for children who had not received an additional booster of the antigens for DTPa-HBV-IPV/Hib following the booster in the 2nd year of life (3+1 schedule);

DTPa, Diphtheria-tetanus-acellular pertussis; ELISA, Enzyme-linked immunosorbent assays; FHA, Filamentous hemagglutinin; HB, Hepatitis B surface antigen; HBV, Hepatitis B
virus; Hib, Hemophilus influenzae type b; IPV, Inactivated polio virus; PRN, Pertactin; PRP, Polyribosylribitol phosphate; PT, Pertussis toxoid
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Figure created from data tables in Data on file, 2014N203547_01
1. Zinke M, et al. Hum Vaccin 2010;6:189–93; 2. GSK. Data on file, 2014N203547_01 – Infanrix hexa persistence data presented in Zinke, et al. 2010;
3. GSK. Data on file, 2014N203547_00 – Infanrix hexa persistence data presented in Zinke, et al. 2010
Up to 15 years of immune persistence to HBV with a
3+1 schedule

Vaccination schedule (months) At 14–15 years of age,

administration of challenge
2 3 4 12–15 dose to mimic HBV
exposure (N=268)2

98.4% 92.5%
(N=2,009) (95% CI 88.7–95.4)
had seroprotective antibody produced an
titers against HBV anamnestic response† to
1 month after booster dose*1 HBV exposure challenge

*Pooled across different primary vaccination schedules

†Anamnestic response was defined as anti-HBs concentrations ≥10 mIU/mL in participants seronegative (anti-HBs antibody concentrations <6.2 mIU/mL) before the challenge dose

and as a ≥4-fold increase in anti-HBs concentrations in participants seropositive (anti-HBs antibody concentrations ≥6.2 mIU/mL) before the challenge dose
HB, Hepatitis B surface antigen; HBV, Hepatitis B virus; CI, confidence interval
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1. GSK. Infanrix Hexa Prescribing Information, Version GDS18/IPI13; 2. Schwarz TF, et al. Hum Vaccin Immunother 2019;15:235–41
A 3-dose primary vaccination schedule provides high
vaccine efficacy against pertussis
German household
Italian randomized, double-blind study2,3
contact study1
Primary schedule (months) Primary schedule (months) 5-year unblinded follow-up
3 5 2 6 at 3–6 years of age3

4 4

88.7% 83.9% 86.0%

vaccine efficacy* vaccine efficacy* vaccine efficacy†

N=22,505 N=4,481 N=4,217

Cases=360 Cases=37 Cases=33

*As of 1 month after dose 3; †At up to 60 months since last priming dose; N, number of patients vaccinated
Please note: these results have been obtained with DTaP Infanrix containing same antigen, in the same amount as Infanrix Hexa: 1,3,4 Equivalence in efficacy is based on the comparison of antibody titres
between Infanrix and Infanrix hexa
DTaP, Diphtheria-tetanus-pertussis
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1. Schmitt HJ, et al. JAMA 1996;275:37–41; 2. Greco D, et al. N Engl J Med 1996;334:341–8; 3. Salmaso S, et al. Pediatrics 2001;108:E81; 4. GSK. Infanrix Hexa Prescribing
Information, Version GDS18/IPI13.
Effectiveness of acellular pertussis vaccination in Madrid, Spain
Vaccine effectiveness with DTaP vaccination with a 3+1 schedule

2 4 6 16–18 months

Reported pertussis cases from 1998 to 2015 (n=3855)*

After 1 year of follow-up, VE: 98.8% (95% CI: 98.3, 99.1) After 12 years of follow-up, VE: 85.1 (95% CI: 81.9, 87.7)

100 500
Vaccine effectiveness (%)

Number of vaccinated
80 400

60 300

cases
Vaccine effectiveness

40 Vaccinated cases 200

20 100

0 0
1 2 3 4 5 6 7 8 9 10 11 12
Follow-up time (years)

A 3+1 schedule was associated with high vaccine effectiveness, which waned gradually over 12 years
To GSK's knowledge, Infanrix hexa was used exclusively from 2007–2015 (no reference currently available)
*88.7% of cases had data on vaccination status; vaccination coverage was 80.5–98.7% for primary immunisation (3 doses) and 74.1–94.9% for the first booster dose (4 doses)
VE was calculated using a screening method based on comparison between the ratio of vaccinated cases and the ratio of the vaccinated population, 1998–2015. Data on vaccination
status was obtained from the Community of Madrid Vaccination Register, which collects nominal information on the vaccines administered throughout its population, with data available
since the end of 2004; VE, vaccine effectiveness

Latasa P et al. Vaccine 2018;36:1643–1649

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The graph has been independently created by GSK using data from the source
Hexavalent vaccines are effective against invasive Hib
disease with a 3-dose schedule
In a German post-marketing study:

Follow-up Vaccine Number of doses Vaccine effectiveness, % (95% CI)

Two hexavalent vaccines 90.4 (70.6–96.8)

5 years1
(including DTaP(3)
(N=2,893)
Hexavalent) 100 (52.7–100)

89.6 (74.4–95.8)
Two hexavalent vaccines
7 years2,3
(including DTaP(3)
(N=2,851)
Hexavalent)
100 (99.9–100)

CI, confidence intervals; Hib, Hemophilus influenzae type b

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1. Kalies H, et al. Vaccine 2008;26:2545–52; 2. Infanrix Hexa Prescribing Information, Version GDS18/IPI13.; 3. GSK. Data on file 2020N436414_00
DTaP(3) hexavalent vaccine was generally well tolerated
in children <2 years of age across several clinical trials1,2
DTaP(3) hexavalent vaccine administered as a 2+1 or 3+1 schedule
Reactions to primary immunization1
20 studies, N=15,095 doses‡
100
Reactions to booster immunization1
Doses followed by a reaction, % (95% CI)†

19 studies, N≤7,719 doses‡

80 Grade 3 reactions*1
or fever >39.5C

Solicited local
60 injection-site reactions Solicited systemic reactions

40

20

0
Pain Redness Swelling Drowsi- Irritability/ Loss of Fever Diarrhea Vomiting Restless- Unusual
ness fussiness appetite ness crying

*Grade 3 reactions defined as: pain, crying when a limb was moved, or spontaneously painful (as per GSK studies); redness and swelling, diameter >20 mm2
†Symptoms reported during the 4- or 8-day post-vaccination period (Days 0–7); ‡Pooled analysis of GSK-sponsored interventional studies

CI, confidence interval

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The graph has been independently created by GSK from: 1.Data on file, 2016N295531_00 – Pooled safety analyses Infanrix hexa as reflected in 2. GSK. Infanrix Hexa
Prescribing Information, Version GDS18/IPI13.;
More than 12 years of post-marketing safety surveillance1
Safety profile of DTaP(3) hexavalent vaccine administered as a 2+1 or 3+1 schedule

No reported interruptions to vaccination

programs due to safety issues* Frequency per 100,000 doses
Fever 2.30
Crying <1.00
Floppiness <0.50
The 10 most frequently spontaneously Pallor
reported events occurred at a frequency Vomiting
of ≤2.3 per 100,000 doses†1 Redness <0.25
Itching
Rash
Cyanosis ≤0.20
>188 million doses delivered globally as of Convulsion
February 20202

*Information correct to the knowledge of GSK

†Reported to OCEANS, GSK’s worldwide safety database*, in a 2+1 schedule with pneumococcal conjugate vaccine co-administration, over a distribution of 92 million doses

OCEANS, Operating Companies Event Accession and Notification System

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1. Baldo V, et al. Hum Vaccin Immunother 2014;10:129–37; 2. GSK. Data on file, 2020N434373_00
SUMMARY
– Immunization has been proven to be effective in reducing
cases
– Must be maintained with high coverage
– The effects of a COVID-19 pandemic have caused low
coverage
– The choice of whole cell or Acellular Pertussis vaccine
depends on your needs

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