Cissy B Kartasasmita

Departemen Ilmu Kesehatan Anak FKUP/RSHS

PERALMUNI
 Prof. Cissy Kartasasmita, dr, MSc, PhD, SpA(K)
§ Guru Besar Departemen ilmu Kesehatan Anak, Fakultas Kedokteran, Universitas
Padjadjaran/Rumah Sakit Hasan Sadikin Bandung

§ Ketua Indonesia Influenza Foundation (IIF)

§ Ketua Pokja Vaksinasi PP PERALMUNI

§ Anggota Satgas Imunisasi IDAI

§ Anggota Indonesia Technical Advisory Group on Immunization (ITAGI)

§ Board Member of APACI ( Asia Pacific Alliance for the Control of Influenza)

§ Board Member of ASAP (Asian Strategic Alliance for Pneumococcal Disease

Prevention)

§ Board Member of CI PP ( Congress of International Pediatric Pulmonology)

§ Board Member of GAN (Global Asthma Network)

OUTLINES
• Introduction
• Burden of Pneumococcal Diseases
• Pneumococcal Diseases During the PCV Vaccination
• History of Pneumococcal vaccination
• Impact of PCV Immunization in Children
• PCV Immunization Program worldwide and in Indonesia
• Take Home Messages
INTRODUCTION
• Streptococcus pneumoniae (SP) related diseases become a leading cause of morbidity and
mortality, especially in children and in the elderly population.
• In Europe and the USA the annual incidence of Invasive Pneumococcal Diseases (IPD) ranges
from 10 to 100 cases per 100,000 people
• Pneumococcal vaccines have been developed over the years and have shown a significant
reduction in mortality, especially in developing countries.
• There is still a debate about the indications given by various countries to different age groups.
• Recommendations for Pneumococcal vaccination are: healthy children 24 through 59 months,
children ages 24 through 71 months with underlying medical condition, and children 6
through 18 years with immunocompromising condition, functional or anatomic asplenia,
cerebrospinal fluid leak, or cochlear implant
• In 2022 BPOM recommend PCV 13 in healthy infant and children age 6 weeks to 17 years old
 Children at risk for pneumococcal disease
Children at increased risk for pneumococcal disease include
§ those younger than 2 years old
§ Chronic heart, lung, or kidney disease
§ Cerebrospinal fluid (CSF) leak
§ Cochlear implant
§ Diabetes
§ HIV infection, cancer, solid organ transplant, or another condition or taking
medicine that weakens the immune system
§ Nephrotic syndrome
§ Sickle cell disease,
§ a damaged spleen, or no spleen
Pneumococcal Disease Can Be Broadly Grouped Into Categories of
Invasive and Noninvasive (Mucosal) Disease

Pneumococcal
Disease1

Noninvasive
Invasive
(Mucosal)

Acute
Meningitis Bacteremia Pneumonia* Sinusitis
Otitis Media

• ~25% invasive*2
• ~75% noninvasive*

• Noninvasive forms may become invasive (eg, pneumonia when accompanied by bacteremia)1

• Disease severity and invasiveness differ based on serotype3

*In adults.
1. World Health Organization (WHO). Wkly Epidemiol Rec. 2012;87(14):129-144. 2. Said MA, et al. PLoS One. 2013;8(4):e60273. 3. Jansen AG, et al. Clin Infect
Dis. 2009;49(2):e23-e29. 6
Common forms of pneumococcal disease
 Pneumococcus: Pathogenesis1-4

Otitis media

Transmission of Meningitis
pneumococcus from
host Bacteremia

Pneumococcal strain
establishes itself in
nasopharynx of host

Pneumonia

1. Centers for Disease Control and Prevention. Pneumococcal disease. In: Hamborsky J, Kroger A, Wolfe S, eds. Epidemiology and Prevention of Vaccine-
Preventable Diseases. 13th ed. Washington, DC: Public Health Foundation; 2015:279-296. 2. Dagan R, et al. J Infect Dis. 2002;185(7):927-936. 3. Simell B, et
al. Expert Rev Vaccines. 2012;11(7):841-855. 4. Henriques-Normark B, et al. Cold Spring Harb Perspect Med. 2013;3(7):a010215. 8
 BURDEN OF DISEASE

After Pneumococcal Conjugate Vaccine (PCV)

Implementation
PNEUMOCOCCAL DISEASES

Pneumococcal pneumonia kills

about 1 in 20 who get it.

Ear infections are usually mild and are more common .

Some children develop repeated ear infections and may need ear tubes.
 Invasive pneumococcal disease
Annual Epidemiological Report for 2018
European Centre for Disease Prevention and Control, 2020 .
In 2018, 24 663 confirmed cases of invasive pneumococcal disease (IPD) were reported in the EU/EEA.
• The crude notification rate was 6.4 cases per 100 000 population, continuing the increasing trend
observed since 2014.
• Age-specific rates were highest in adults aged 65 years or older (18.7 confirmed cases per 100 000
population) and in infants under one year (14.4 confirmed cases per 100 000 population), with higher
rates reported in males than females.
• The 10 most common serotypes were 8, 3, 19A, 22F, 12F, 9N, 15A, 10A, 23B and 6C (in order of
decreasing frequency), accounting for 70% of typed isolates.
• Of all the cases under five years of age, 75% were caused by a serotype not included in any
pneumococcal conjugate vaccine (PCV).
• Among cases aged 65 years and over, 73% were caused by serotypes included in the 23-valent
polysaccharide vaccine and 29% were caused by serotypes in the 13-valent PCV.
Distribution of confirmed invasive pneumococcal disease cases per 100 000
population by country, EU/EEA, 2018

Source: Country reports from Austria,

Bulgaria, Croatia, Cyprus, the Czech
Republic, Denmark, Estonia, Finland, France,
Greece, Hungary, Iceland, Ireland, Italy,
Latvia, Lithuania, Luxembourg, Malta, the
Netherlands, Norway, Poland, Portugal,
Romania, Slovakia, Slovenia, Spain, Sweden
and the United Kingdom.
 Distribution of confirmed invasive pneumococcal disease cases
per 100 000 population, by age and gender, EU/EEA, 2018
In 2018, IPD was predominantly reported in the elderly and in
infants, with 18.7 confirmed cases per 100 000 population in adults
aged 65 years and above, and 14.4 confirmed cases per 100 000
population in infants under one year (Figure 2). The rates of disease
were the lowest in persons aged 5–24 years (0.8 confirmed cases per
100 000 population). The notification rate was higher in males in all
age groups. The overall male-to-female ratio was 1.2:1.
Distribution of confirmed invasive pneumococcal disease cases
by month, EU/EEA, 2014–2018
Countries included: Austria, Cyprus, Czechia, Denmark, Estonia,
Finland, France, Greece, Hungary, Ireland, Iceland, Italy, Latvia,
Lithuania, Malta, the Netherlands, Norway, Poland, Romania,
Slovenia, Slovakia, Spain, Sweden and the UK.
Distribution of confirmed serotyped cases of invasive pneumococcal disease:
most common S. pneumoniae serotypes in 2018

8^ 3^ 19A^ 22F^ 12F^. 9N^ 15A 10A^ 23B 6C

2014 - 2015 – 2016 - 2017 - 2018

Source: Country reports from Austria, the Czech Republic, Denmark, Estonia, Finland, France, Greece, Hungary, Iceland, Ireland, Italy,
Latvia, Lithuania Distribution of confirmed serotyped cases of invasive pneumococcal disease: most common S. pneumoniae serotypes in
20181 , the Netherlands, Norway, Portugal, Slovakia, Slovenia, Spain, Sweden and the United Kingdom.
 Cases in Indonesia Total Estimated

S.pn pneumonia 585,770

S.pn severe pneumonia 230,600

S.pn meningitis 2,480

S.pn non-pneumonia non-meningitis 2,816

S.pn non-pneumonia non-meningitis non-severe 7,488

• Globally Pneumococcal death in children aged 1-59 months:

600,000 in 2000 decline to 294,000 in 2015
Wahl B, O'Brien K, Greenbaum A, et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type b disease in children in the era of conjugate
vaccines: global, regional, and national estimates for 2000–15. Lancet Glob Health 2018;6:e744-57
Karier Nasofaring di Padang, Bandung, Lombok
Universitas Padjajaran, Universitas Andalas, Universitas Mataram, Murdoch Children’s Research Institute, The University
of Melbourne, London School of Hygiene and Tropical Medicine, PATH

Anak usia 12-24 bulan: 20 serotype paling sering per daerah

PCV13 coverage
Overall 76/164 (46.3%):
Bandung 26/73 (36%)
Lombok 28/53 (53%)
Padang 22/38 (58%)

Dunne EM, Murad C, Sudigdoadi S, et al. OneCarriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus
aureus in Indonesian children: A cross-sectional study. Plos One 2018;13(4): e0195098.
IMPACT OF PCV IMMUNIZATION
The overall IPD incidence declined
from 95 cases per 100,000 in 1998 to
7 cases per 100,000 in 2018; IPD
caused by PCV13 serotypes declined
from 88 cases per 100,000 in 1998 to
2 cases per 100,000 in 2019.
 The Impact of Pneumococcal Conjugate Vaccine (PCV) Coverage
Heterogeneities on the Changing Epidemiology of Invasive Pneumococcal
Disease in Switzerland, 2005–2019.
Oyewole OR-A, et. Al (2021)

Abstract
Pneumococcal conjugate vaccines (PCVs) have lowered the incidence of invasive pneu- mococcal disease (IPD)
worldwide. However, the influence of regional vaccine uptake differences on the changing epidemiology of IPD
remains unclear. We aimed to examine the overall impact of both seven- and 13-valent PCVs (PCV7 and PCV13) on
IPD in Switzerland. Three-year periods from 2005–2010 and 2011–2019 were considered, respectively, as (early and
late) PCV7 eras and (early, mid and late) PCV13 eras. Vaccine coverage was estimated from a nationwide survey
according to east (German-speaking) and west (French/Italian-speaking) regions for each period. Reported
incidence rate ratios (IRRs) were compared between successive periods and regions using nationwide IPD
surveillance data. Overall IPD incidence across all ages was only 16% lower in the late PCV13 era compared to the
early PCV7 era (IRR 0.83, 95% CI 0.79–0.88), due to increasing incidence of non-PCV-type IPD (2.59, 2.37–2.83) in all
age groups, except children <5 years. PCV uptake rates in swiss children were slightly higher in the west than the
east (p < 0.001), and were accompanied by lower IPD incidences across all age groups in the former region. Post-
PCV13, non-PCV serotypes 8, 22F and 9N were the major cause of IPD in adults ≥65 years. Increased PCV coverage
in both areas of Switzerland resulted in a decrease in vaccine-type and overall IPD incidence across all age groups, in
a regionally dependent manner. However, the rising incidence of non-vaccine-type IPD, exclusive to older adults,
may undermine indirect beneficial effects.
Microorganisms 2021, 9, 1078. https://doi.org/10.3390/microorganisms9051078 https://www.mdpi.com/journal/microorganisms
 Changes in Invasive Pneumococcal Disease Spectrum After 13-Valent
Pneumococcal Conjugate Vaccine Implementation.
Levy C et al. (2020)
• Background. Pneumococcal conjugate vaccine (PCV) implementation has led to a sharp decrease in invasive pneumococcal disease
(IPD) due to the reduction in PCV serotypes. We aimed to describe the changes in the spectrum of IPD and its clinical presentations
after 13-valent PCV (PCV13) implementation.

• Methods. This prospective, hospital-based, active surveillance involved 130 pediatric wards and microbiology departments
throughout France. We analyzed IPD cases from 2011 to 2016 for which a pneumococcal isolate was sent to the National Reference
Center for Pneumococci for serotyping. Clinical data recorded were medical history, vaccination status, type of IPD, clinical features,
and short-term evolution.

• Results. Among 1082 IPD cases, we observed a 35.3% decrease (95% confidence interval, 29.2%–41.8%]) and the median age
shifted from 38.3 months to 23.7 months (P = .007). The change in IPD type was mostly due to a reduction in bacteremic
pneumonia frequency (from 42.1% to 19.1%; P < .001). Among the emerging non-PCV13 types (NVTs), those known to have the
highest disease potential (8, 12F, 24F, and 33F) were isolated more frequently in patients without underlying conditions and were
able to induce all IPD clinical presentations including bacteremic pneumonia. Conversely, serotypes with lower disease potential
(15A, 15BC, 16F, and 23B) were rarely isolated from bacteremic pneumonia cases and were particularly involved in IPD in patients
with underlying conditions (35.8%).

• Conclusions. Besides the decrease in IPD after 7-valent, then 13-valent PCV implementation, the
spectrum of the remaining IPD cases showed significant changes, with substantial discrepancies across
NVTs implicated in terms of clinical features and un- derlying conditions. cid 2020:70 (1 February)
 Impact of 13-valent pneumococcal conjugate vaccine
on laboratory-confirmed pneumococcal meningitis and purulent
meningitis among children.
Libwea JN et al.
Results
• Among children hospitalized with CSBM who had a lumbar puncture obtained, there was no significant change from the
EPE versus the LPE in the percentage identified with purulent meningitis: 7.5% (112/1486) versus 9.4% (154/1645), p =
0.0846. The percentage of pneumococcal meningitis cases due to PCV13 vaccine-serotype (VST) decreased from 62.0%
(31/50) during the EPE to 35.8% (19/53) in the LPE, p = 0.0081. The most frequent pneumococcal meningitis VSTs during
the EPE were 6A/6B (30%) and 5 (6%), and during the LPE were 14 (13.2%), 3 (7.6%), 4 (5.6%) and 18C (5.6%).
Conclusion
• Four to seven years after PCV13 introduction, the proportion of pneumococcal meningitis due to
vaccine serotypes has declined, mainly due to reductions of serotypes 6A/6B, 1, 19A, and 23F;
nevertheless, PCV13 VSTs remain common.
• Because the analyzed surveillance system was not consistent or population based, we could not
estimate incidence or overall impact; this emphasizes the need for improved surveillance to
document further the utility of PCV13 immunization in Cameroon.
•Published: April 15, 2021
•https://doi.org/10.1371/journal.pone.0250010
 13-valent Pneumococcal Conjugate Vaccine in Older Children and Adolescents Either
Previously Immunized With or Naïve to 7-valent Pneumococcal Conjugate Vaccine

Background: The 13-valent pneumococcal conjugate vaccine (PCV13) has been demonstrated to be immunogenic and safe
for administration to infants and children aged <5 years. PCV13 recently was approved for children and
adolescents aged up to 17 years as the vaccine may be of benefit to some in this older age group.

Methods: In this open-label study, healthy children aged ≥5 to <10 years (ie, the younger age group) previously vaccinated
(≥1 dose) with 7-valent PCV (PCV7) and pneumococcal vaccine-naïve children aged ≥10 to <18 years (ie, the older age
group) received 1 dose of PCV13. For the younger group, antipneumococcal immunoglobulin (Ig) G geometric mean
concentrations 1 month postvaccination were compared with posttoddler dose (PCV13 or PCV7) levels from a historical
control study. Opsonophagocytic activity geometric mean titers 1 month postvaccination for the older group
were compared with the younger age group. Safety data were collected.

Results: Five hundred and ninety-eight children were enrolled, 299 in each age group. For PCV7 serotypes, IgG geometric
mean concentrations in the younger group were 8.23–53.56 μg/mL, ≥2.5-fold greater than historical posttoddler dose values.
For the 6 additional serotypes, IgG geometric mean concentrations in the younger group were 2.38–21.51 μg/mL, ≥1.2-fold
greater than historical posttoddler dose values. Opsonophagocytic activity geometric mean titers were similar in the older
and younger age groups, except for serotype 3 which was lower in the older group. Safety was comparable in both groups.

Conclusions: PCV13 was immunogenic and safe when administered to older children and adolescents,
regardless of prior PCV7 vaccination.
A phase 3, multicenter, single-arm, open-label study to assess the safety, tolerability,
and immunogenicity of a single dose of 13-valent pneumococcal conjugate vaccine in
Japanese participants aged 6–64 years who are considered to be at increased risk of
pneumococcal disease and who are naive to pneumococcal vaccines
Background: This open-label, single-arm, phase 3 study evaluated safety and immunogenicity of the 13-valent pneumococcal conjugate vaccine
(PCV13) in pneumococcal vaccine-naive Japanese individuals aged 6–64 years at increased risk of pneumococcal disease (PD).
Methods: Participants received 1 PCV13 dose. Reactogenicity events were recorded for 7 days (individuals aged 6- to 17-year-old) or 14 days
(individuals aged 18 to 64 years old) postvaccination. Adverse events (AEs) were collected for 1 month postvaccination. Opsonophagocytic
activity (OPA) and anticapsular immunoglobulin G (IgG) geometric mean concentrations (GMCs) were measured for vaccine serotypes before and
1 month postvaccination. Post hoc analyses compared immunogenicity in participants categorized as at-risk (immunocompetent but having
chronic medical conditions associated with increased PD risk) or high-risk (immunocompromised due to diseases/conditions and/or
medications).
Results: 206 participants aged 6- to 17-year-old (n = 53) and 18 to 64 years old (n = 153) completed the study. Reactogenicity events were
generally mild to moderate in severity. AEs were reported in 16% (33/206) of participants; 1.0% (2/206) were severe. Six AEs were vaccine-
related; most were associated with local reactions. No serious AEs occurred. Circulating antibody levels for all 13 serotypes increased
postvaccination. OPA geometric mean fold rises (GMFRs) from prevaccination to 1 month postvaccination were 5.5–61.7; lower limits of the 2-
sided, 95% CI were > 1 for all serotypes. IgG GMFRs were consistent with OPA analyses. In post hoc analyses, 55.8% (115/206) and 44.2%
(91/206) of participants were categorized as at risk and at high risk of PD, respectively; OPA GMFRs from prevaccination to 1 month
postvaccination were 3.9–635.1, with lower limits of the 2-sided 95% CIs > 1 for all 13 serotypes across these risk groups; IgG GMFRs were
consistent with OPA analyses.

Conclusions: PCV13 was well tolerated and immunogenic in Japanese individuals aged 6–64 years
considered at increased risk of PD. Results were broadly comparable with past PCV13 studies in other
Japanese and non-Japanese populations.
https://doi.org/10.1016/j.vaccine.2021.08.106
0264-410X/ 2021 Elsevier Ltd. All rights reserved.
Long-term Immune Responses to Pneumococcal Conjugate Vaccines in Children
Previously Vaccinated With 7-valent Pneumococcal Conjugate Vaccine

Background: Seven-valent pneumococcal conjugate vaccine (PCV7) has reduced incidence of vaccine-serotype
pneumococcal diseases. Using a single dose of 13-valent pneumoccal conjugate vaccine (PCV13), we evaluated late
immune responses 10 years after vaccination with PCV7 in infancy, compared with a PCV7-naïve cohort.
Methods: In this open-label study, we administered 1 dose of PCV13 to children aged 11–14 years who had previously
received PCV7 (PCV7/ PCV13) or meningococcal group C conjugate vaccine (MnCC/PCV13) during infancy. We evaluated
serotype-specific immunoglobulin G concentrations and opsonophagocytic activity prevaccination and 1 week and 1
month postvaccination. We recorded local reactions and systemic events for 4 days postvaccination and adverse events
for 6 months.
Results: Seventy-four subjects received PCV13 (PCV7/PCV13, n = 38; MnCC/PCV13, n = 36). Prevaccination with PCV13,
>62.9% of subjects had immunoglobulin G concentrations ≥0.35 μg/mL for all serotypes except serotype 4 (28–29%);
proportions increased at 1 month postvaccination to 100% for all serotypes except serotypes 3 (PCV7/PCV13, 94.7%;
MnCC/PCV13, 97.0%) and 14 (MnCC/PCV13, 97.1%). Immunoglobulin G and opsonophagocytic activity concentrations
for the 7 common and 6 additional serotypes were similar in both groups prevaccination and increased in both groups
from prevaccination to 1 week and 1 month postvaccination. Local reactions and fever were mild or moderate; no
serious adverse events were reported.

Conclusion: Late immune responses after a single dose of PCV13 were similar in children aged 11–14 years
regardless of previous vaccination with PCV7 or MnCC. PCV13 was immunogenic, safe and well tolerated.
IMPACT OF PCV IMMUNIZATION
IN CHILDREN < 15 YEARS
 PCV13 2+1

France: Pneumococcal CAP*† Cases in Children 1 Month–15 Years of Age

in 8 Pediatric Hospitals
Pneumococcal CAP (children 1 month–15 years of age)

Pneumococcal CAP
100
Number of Cases

50

63% reduction
vs pre-PCV13

0
Pre-PCV13 Transition Post-PCV13
(June 2009–May 2010) (June 2010–May 2011) (June 2011–May 2012)

*X-ray confirmed; laboratory-confirmed P-CAP defined by positive blood or pleural culture, positive pleural PCR, or positive pneumococcal antigen detection in pleural sample.
†Microbiologically confirmed.

CAP=community-acquired pneumonia; P-CAP=pneumococcal CAP; PCR=polymerase chain reaction.

Angoulvant F, et al. Clin Infect Dis. 2014;58(7):918-924. 26
 PCV13 2+1

France: Cases of Pneumonia* With Pleural Effusion in Children

1 Month–15 Years of Age in 8 Pediatric Hospitals
Pneumonia with pleural effusion (children 1 month–15 years of age)

Pleural effusion
200
Number of Cases

100
52.7% reduction
vs pre-PCV13

0
Pre-PCV13 Transition Post-PCV13
(June 2009–May 2010) (June 2010–May 2011) (June 2011–May 2012)

*X-ray confirmed.
Angoulvant F, et al. Clin Infect Dis. 2014;58(7):918-924. 27
 PCV13 2+1

Argentina: Impact of PCV13 Vaccination on Consolidated Pneumonia

in Children ≤15 Years of Age
Discharge rates and percent reduction for consolidated pneumonia by age, 2007–2014
40.1%
(34.5%–45.1%)
15.8%
(9.5%–21.6%) 22.2%
(per 10,000 hospital discharges)

20.5%
(15.5%–28.3%)
1000 (13.4%–27.1%)
10.4%
(4.3%–16.2%)
2.1%
800 (-5.8%–9.3%)
Discharge rates

Pre-vaccination period (2007–2011)*

600 13.8%
(5.2%–21.6%) Intervention period (2012)

2.9%
Post-vaccination period (2013–2014)*
400
(-6.3%–11.2%)

200

0
0–11 months 12–23 months 24–59 months 5–15 years
Age group
• There was an overall 24.8% decrease in discharge rates related to consolidated pneumonia between the pre- and the post-vaccination
periods, with the largest decrease (40.1%) seen in children 12 to 23 months of age

*Data shown correspond to annual averages.

Gentile A, et al. PLoS One. 2018;13(7):e0199989. 28
 PCV13 2+1

Argentina: Impact of PCV13 Vaccination on Pneumococcal Pneumonia

in Children ≤15 Years of Age
Discharge rates and percent reduction for pneumococcal pneumonia by age, 2007–2014
64.3%
(44.9%–76.9%)
77.6%
(59.6%–87.6%) 42.3%
(per 10,000 hospital discharges)

(18.2%–59.4%)
50 70.5%
(40.4%–82.8%)
66.2%
(43.6%–79.8%)
40 56.3%
71.8%
Discharge rates

(35.0%–70.6%)
(53.1%–83.0%)
Pre-vaccination period (2007–2011)*
51.7%
30
(30.0%–66.7%)
Intervention period (2012)

20 Post-vaccination period (2013–2014)*

10

0
0–11 months 12–23 months 24–59 months 5–15 years
Age group

• There was an overall 68.8% decrease in discharge rates related to pneumococcal pneumonia between the pre- and post-vaccination periods,
with the largest decrease (77.6%) seen in children 12 to 23 months of age

*Data shown correspond to annual averages.

Gentile A, et al. PLoS One. 2018;13(7):e0199989. 29
 PCV13 2+1

Uruguay: Hospitalizations for Bacterial-Confirmed Pneumonia

in Children 0–14 Years of Age
H influenzae b
(Hib) (1994)
Incidence per 10,000 Discharges

120

100

80

60 87.7%*
PCV7
PCV13
40

20

0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Year

*Significant reduction.
Pirez MC, et al. Pediatr Infect Dis J. 2014;33(7):753-759. 30
 PCV13 2+1

Uruguay: Hospitalizations for Pneumococcal CAP

in Children 0–14 Years of Age
Incidence per 10,000 Discharges

90

80

70

60

50
PCV7 90.4%*
40 PCV13

30

20

10

0
2003 2004 2005 2006 2007 2008 2009 2010 2011 2012
Year
• A significant 95% reduction in discharges for P-CAP caused by 6 additional serotypes in PCV13 was observed between the periods prior to
and after PCV7/13 implementation
*Significant reduction.
CAP=community-acquired pneumonia.
Pirez MC, et al. Pediatr Infect Dis J. 2014;33(7):753-759. 31
 PCV13 3+1

United States: IPD Cases Caused by the PCV13 Serotypes (plus 6C)
in Children <18 Years of Age
United States, PCV13 serotype IPD
PCV13
350
<5 years of age
5–17 years of age
300

250
Cases per Year

200

150 (2009–2010 vs 2012–2013)

89% reduction in
100 <5 years of age

50 68% reduction in
5–17 years of age

0
2004–05 2005–06 2006–07 2007–08 2008–09 2009–10 2010–11 2011–12 2012–13
Year

Moore MR, et al. Lancet Infect Dis. 2015;15(3):301-309. 32

 PCV13 3+1

United States: IPD Caused by the Additional Serotypes in PCV13 (not in PCV7)
in Children <18 Years of Age
United States, PCV13 minus PCV7 serotype IPD*
PCV13
350
<5 years of age
5–17 years of age
300

250
Cases per Year

200

150 (2009–2010 vs 2012–2013)

100 91% reduction

50 72% reduction

0
2004–05 2005–06 2006–07 2007–08 2008–09 2009–10 2010–11 2011–12 2012–13
Year

*Includes serotypes 1, 3, 5, 7F, and 19A; serotype 6A is considered a PCV7-related serotype by the US CDC.
Moore MR, et al. Lancet Infect Dis. 2015;15(3):301-309. 33
 PCV13 2+1
Uruguay: Impact of PCV7/13 on Pneumococcal Meningitis (PM)
in Children Aged <15 Years
Average annual hospitalization rates and case fatality rates due to PM
by any serotype among children <15 years of age, 2005–2014
P<0.0001 P=0.07
8 60

7 71% reduction
50
per 10,000 discharges

in mortality
6

Case fatality rate

63.5% reduction in
Hospitalized PM

hospitalized PM 40
5

4 30

3
20
2
10
1

0 0
Pre-vaccination era Post-vaccination era Pre-vaccination era Post-vaccination era
(2005–2007) (2009–2014) (2005–2007) (2009–2014)

• In children <15 years of age, the annual average rate of PM hospitalizations declined by 63.5% during the post-PCV era relative to before
PCV introduction
• A 71% reduction in mortality due to PM was observed in the post-vaccination era in children younger than 15 years of age
Pre-vaccination period (before PCV7/13) extended from January 1, 2005 to December 31, 2007. 2008 was the transition year, and the post-vaccination period went from January 1, 2009 to December 31, 2014.
Pírez MC, et al. Pediatr Infect Dis J. 2017;36(10):1000-1001. 34
 PCV13 2+1

Uruguay: Impact of PCV7/13 on Pneumococcal Meningitis (PM)

in Children Aged <15 Years
Average annual rate of PM hospitalizations due to vaccine
and non-vaccine serotypes among children <15 years, 2005–2014
7 P<0.0001
Pre-vaccination (2005–2007)
per 10,000 discharges 6
Post-vaccination (2011–2014)
Hospitalized PM

3
NS
2

0
PCV13 serotypes Nonvaccine serotypes

• The annual average rate of hospitalized PM due to PCV13 serotypes significantly declined by ~90% during the post-vaccine era in children
younger than 15 years of age
Pre-vaccination period (before PCV7/13) extended from January 1, 2005 to December 31, 2007. 2008 was the transition year, and the post-vaccination period went from January 1, 2009 to December 31, 2014.
NS=not significant.
Pírez MC, et al. Pediatr Infect Dis J. 2017;36(10):1000-1001. 35
 History of Pneumococcal Vaccines
1880 1916–1917
Isolation of S pneumoniae Dochez and Avery isolate
by Sternberg and Pasteur pneumococcal capsular
polysaccharides 2000
First approval of
pneumococcal
1911–1912 1929 conjugate vaccine
Wright carries out trials Avery conjugates
of whole-cell heat-killed pneumococcal
pneumococcal vaccine polysaccharides
in several thousand to proteins in
patients animal models

1914
Lister recognizes 1977 1983
pneumococcal types & PPV14 PPV23
develops first serotype- approved* approved*
specific whole-cell
pneumococcal vaccines
1944–1945
MacLeod and Heidelberger
demonstrate efficacy of
quadrivalent PPSV
*US approval.
Grabenstein JD, Klugman KP. Clin Microbial Infect. 2012;18(suppl 5):15-24. 36
 History of PCV13 Licensure and Recommendations
in the United States and European Union
2011 2014
PCV13 licensed for adults aged ≥50 years ACIP recommends PCV13
for prevention of IPD and pneumonia
for all adults ≥65 years2
under accelerated approval pathway2
US
2010 2012
ACIP recommends PCV13 2016
PCV13 licensed CAPiTA trial
PCV13 indication expanded
for use in children2 for immunocompromised completed2
adults ≥19 years2 to include adults ≥18 years5

2013
2009 PCV13 indication extended to
PCV13 licensed
for use in children1 include adults ≥18 years for
prevention of IPD3
EU 2015
2011 EMA approves
PCV13 licensed for adults ≥50 years for prevention of expanded indication for
IPD only, as EMA would not grant an indication for prevention of pneumonia
PCV13 for non-invasive disease based on serological in adults ≥18 years3
bridging to PPV233,4

ACIP=Advisory Committee on Immunization Practices; CAPiTA=Community-Acquired Pneumonia Immunization Trial in Adults; EMA=European Medicines Agency.
1. Prevenar 13 [summary of product characteristics]. Kent, United Kingdom: Pfizer Limited; 2014. 2. CDC. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6337a4.htm.
Accessed June 30, 2017. 3. European Medicines Agency. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-
_Procedural_steps_taken_and_scientific_information_after_authorisation/human/001104/WC500096015.pdf. Accessed July 6, 2017. 4. European Medicines Agency.
http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Assessment_Report_-_Variation/human/001104/WC500119784.pdf. Accessed June 30, 2017.
5. Pfizer press release. Pfizer receives FDA approval for Prevnar 13® in adults age 18 through 49. http://www.pfizer.com/news/press-release/press-release-
detail/pfizer_receives_fda_approval_for_prevnar_13_in_adults_age_18_through_49. Accessed June 30, 2017. 37
PCV in Pediatric Immunization Program Worldwide1,2

PCV13 Only* = 121

PCV13 / PCV10† Shared = 6

(PCV13 covers >50% of total BC)

PCV13 / PCV10† Shared = 1

(PCV13 covers <50% of total BC)

PCV10 Only = 31
As of February 2020

PCV13 Is Included in Over 125 NIPs, With Exclusivity in 121 Countries Worldwide
Picture adapted from 1. Gavi Alliance Annual Progress Report 2017. https://www.gavi.org/sites/default/files/publications/progress-
reports/Gavi-Progress-Report-2017.pdf Accessed July 29, 2020. 2. Data on file. Pfizer Inc, New York, NY. 2020.
*Canadian province of Quebec and Italian region of Piemonte have initiated PCV vaccination programs with PCV10.
†Both PCVs are available/reimbursed in the NIP or the NIP consists of different PCVs by region. BC=birth cohort.
13 Years of Heritage supporting Pneumococcal Disease Prevention
in Indonesia

PCV 7 Launch
• Extensive CMEs and Vaccinology Training in
every province in Indonesia.

• Pneumococcal disease prevention awareness

education towards Parents and Health Care PCV13 Launch
Professionals • PCV13 launched as the broadest coverage
PCV

PCV13 Indication extended to • Media education on the public health

cover Adults / Peds Data @ ISPPD importance of pneumococcal disease
prevention
• PCV13 adult indication approved (only PCV
with adult indication)

• Indonesia Pediatric Nasopharyngeal Carriage PCV Demonstration Program in

data presented in ISPPD Hyderabad Lombok and Bangka Belitung
• PCV13 selected for Indonesian PCV
Demonstration project.
PCV Access for Indonesia • CMEs, Vaccinology and Safety Training
• Commited to successful PCV introduction in conducted during introduction period
for the children of Indonesia

• Nationwide CMEs, Trainings, Workshops,

Capacity Building, logistic and supply support

Nationwide

Confidential. Not for further Distribution. 39

 Indikasi lama yang disetujui
(persetujuan BPOM 16 Mei 2021)
Bayi dan anak usia 6 minggu hingga 5 tahun:
Imunisasi aktif untuk pencegahan penyakit invasif,
pneumonia, dan otitis media akut yang disebabkan
oleh bakteri streptococcus pneumoniae.
Dewasa usia 50 tahun ke atas:
Imunisasi aktif untuk pencegahan penyakit
pneumokokus (termasuk pneumonia dan penyakit
invasif).
Indikasi baru yang disetujui
(Persetujuan BPOM 9 Mei 2022)5
Bayi, anak, dan remaja usia 6 minggu hinga 17 tahun:
Imunisasi aktif untuk pencegahan penyakit invasif,
pneumonia, dan otitis media akut yang disebabkan
oleh bakteri Streptococcus pneumoniae.
Dewasa usia 18 tahun ke atas:
Imunisasi aktif untuk pencegahan penyakit
pneumokokus (termasuk pneumonia dan pneumonia
invasif).
Safety and Immunogenicity of 13-Valent Pneumococcal Conjugate Vaccine
in Children 6–17 Years of Age in India

Abstract: In an open-label study in India, 200 healthy participants 6–17 years

of age received 13-valent pneumococcal conjugate vaccine (PCV13). PCV13
elicited robust functional antibody immune responses. No adverse events
were reported by caregivers at the 1-month follow-up visit. The
immunogenicity results together with the known favorable risk–benefit
profile of PCV13 support extension of the indication to this age group in India
 TAKE HOME MESSAGES

• Streptococcus pneumoniae (SP) is a leading cause of morbidity and mortality,

especially in children and in the elderly population.
• Globally Pneumococcal death in children aged 1-59 months: 600,000 in 2000
decline to 294,000 in 2015
• Pneumococcal vaccines have been developed over the years and shown a
significant reduction in mortality, especially in developing countries
• BPOM approved age expansion indication for PCV, which previously approved
for 6 weeks – 5 yo , now PCV approved for children age 6 weeks-17 yo
43