INFEKSI PNEUMOKOKUS

DAN PENCEGAHANNYA
Andy Setiawan
Pneumococcal Disease
•First isolated by Pasteur in 1881
•Confused with other causes of pneumonia until
discovery of Gram stain in 1884
•More than 90 serotypes described
•Two classes of pneumococcal vaccines are currently
available
Streptococcus pneumoniae: The Bacterium Responsible
for Pneumococcal Disease
• A leading cause of pneumonia, meningitis,
and bacteremia

• Organism has an outer polysaccharide layer

– Defines the serotype
– Functions as virulence factor
– Is a vaccine target

• More than 90 serotypes of S pneumoniae have

Serotype 19F; photograph courtesy of Robert
P. Smith, MS, Senior Research Scientist, been identified
Wyeth Vaccines.
– Serotypes are not equally pathogenic

• Antibiotic resistance in S pneumoniae is a

global concern

• Exclusively human pathogen commonly carried

in the nasopharynx

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. 3
• Streptococcus pneumoniae can asymptomatically colonize the
nasopharynx and cause a diverse range of illnesses.
• This clinical spectrum from colonization to invasive pneumococcal
disease (IPD) appears to depend on the pneumococcal capsular
serotype.
• Serotypes 1, 4, 5, 7F, 8, 12F, 14, 18C, and 19A are more likely to cause
IPD
• Pneumococcal epidemiology of capsule types varies geographically --
> nationwide serosurveillance system is vital to establishing appropriate
vaccination strategies for each country.
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3546102/#:~:text=(66)%20also%20reported%20that%20the,true
%20prevalence%20of%20serotype%2014.
 Epidemiology
• Reservoir : Human carriers
• Transmission : Respiratory à "Autoinoculation“
• Temporal pattern : Winter and early spring
• Communicability : Unknown, probably as long as organism in
respiratory secretions
Invasive Pneumococcal
Disease: Incidence by Age Group
250

200

150
Rate

100

50

0
<1 1 2 3 4 5-17 18-34 35-49 50-64 65+
Age Group (Yrs)
 The Burden of Pneumococcal Disease in Children

Meningitis Invasive
Bacteremia/sepsis Pneumococcal
Bacteremic pneumonia Disease (IPD)
y
rit

ce

Pneumonia
ve

• Most common cause of vaccine-

en
Se

preventable death in the U.S.

al
ev

• Most common cause of bacterial

Pr

meningitis among infants and young

Otitis media children
• Increasing antibiotic resistance

Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. In:
7
Hamborsky J, Kroger A, Wolfe S, eds. 13th ed. Washington, DC: Public Health Foundation; 2015. 7
Underlying Cause of Death in Children
Aged 0 - 11 months and 0-59 months
N
Causes of Death (ICD 10) % No Causes of Death (ICD 10) %
o
Disorders relating to length of gestation Disorders relating to length of gestation 14.
1 18.9 1
and fetal growth (P05 – P08) and fetal growth (P05 – P08) 0
Intrauterine hypoxia and birth asphyxia Diarrhoea and gastroenteritis of
2 14.8 2 11.1
(P20, P21) presumed infectious origin (A09)
3 Pneumonia (J12 – J18) 9.7 Intrauterine hypoxia and birth asphyxia
3 11.0
Diarrhoea and gastroenteritis of (P20, P21)
4 9.2
presumed infectious origin (A09) 4
e a th in
Pneumonia (J12 – J18) 9.5
Congenital malformations of the heart o f d of the heart
Congenital malformations
e
5 5.8 5
(Q20 g- caus
Q24)
5.9
(Q20 - Q24)
e rlyin
6 Respiratory distress of newborn (P22) ain
d
4.3un 6 d e r-five(G03)
Meningitis 3.5
th em n d unRespiratory distress of newborn (P22)
7 3.2
i i
Fetus and newborn affectedaby s maternal
n ts a
m o n in fa Accidental drowning and submersion
7 P e u
factors and byncomplications of
2.4 8 2.0
pregnancy labour and delivery (P00 – (W65 – W74)
P04) Fetus and newborn affected by maternal
8 Meningitis (G03) 2.2 factors and by complications of
9 1.9
Haemorrhagic and haematological pregnancy labour and delivery (P00 –
9 disorders of fetus and newborn (P50 – 1.7 P04)
P61) 10 Diseases of the digestive system (K56) 1.5
Litbangkes
10 Kemkes RI.
Diseases ofIndonesia Sample Registration
the digestive system System 2015. Lembaga
(K56) 1.4Penerbitan Balitbangkes. 2017: pg.21
Vaccine-Preventable Pneumonia in Children <5 Years
of Age Worldwide

3.520.700
S
S pneumoniae
pneumoniae
257.000

298.000
Hib Severe episodes
22.600
Deaths

0 3.000.000 6.000.000

2015 global estimates

• S pneumoniae is a leading cause of vaccine-preventable pneumonia, estimated to be

responsible for ~34% of pneumonia deaths worldwide

Hib=Haemophilus influenzae type b.

Wahl B, et al. Lancet Glob Health. 2018;6(7):e744-e757. 9
Indonesia: Pneumonia facts
• Unicef 2018
• Leading cause of death in
Indonesian under five
• 71 children get pneumonia, with
2 deaths every hour
• Kemenkes 2019
• 153.987 cases under 1 yo
• 314.455 cases in 1-5 yo
• 7th highest country with
pneumonia burden
Pneumococcal Disease:
Pneumonia
Meningitis
Pneumococcal Bacteremia
• More than 50,000 cases per
year in the United States
• Rates higher among elderly
and very young infants
• Case fatality rate ~20%; up
to 60% among the elderly
Vaccines
• 1977 : 14-valent polysaccharide vaccine licensed
• 1983 : 23-valent polysaccharide vaccine licensed
• PNEUMOVAX 23 is a vaccine indicated for active immunization for the prevention of
pneumococcal disease caused by the 23 serotypes contained in the vaccine (1, 2, 3, 4, 5, 6B, 7F,
8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F, and 33F).
• 2000 : 7-valent polysaccharide conjugate vaccine licensed
• 2010 :13-valent pneumococcal conjugate vaccine (PCV13) was licensed
• 2012 : 10-valent pneumococcal conjugate vaccine (PCV10) was licensed
Vaccines
• Two classes of vaccines are currently available:
• Polysaccharides:
• Consists of purified capsular polysaccharides from the 23 serotypes
• Coverage about 90% of invasive pneumococcal infection in industrialized countries
• Responses are age-dependent and serotype-dependent.
• Polysaccharides "conjugated" to a carrier protein
• At first, contain polysaccharides from 7 serotypes
• Coverage 65–80% of serotypes associated with invasive pneumococcal disease
• Conjugated to a carrier protein which makes them more immunogenic and effective in
protecting against infection, in particular in young children less than 2 years of age
• Furthermore, the vaccine protects against both systemic and mucosal infection and
prevents nasopharyngeal colonization, thereby reducing transmission in the
community.
Polysaccharide Vaccine
•Purified pneumococcal polysaccharide (23 types)
•Not effective in children <2 years
•Account for 88% of bacteremic pneumococcal disease
•Cross-react with types causing additional 8% of disease
•60%-70% against invasive disease
Polysaccharide Vaccine
Recommendations
•Adults >65 years of age
•Persons >2 years with
• chronic illness
• anatomic or functional asplenia
• immunocompromised (disease, chemotherapy, steroids)
• HIV infection
• environments or settings with increased risk
Licensed Pneumococcal Conjugate Vaccines
4 6B 9V 14 18C 19F 23F
PCV71
CRM

4 6B 9V 14 18C 19F 23F 1 5 7F

PCV102
Protein D TT DT Protein D

4 6B 9V 14 18C 19F 23F 1 5 7F 3 6A 19A

PCV133
CRM

• Development and licensure of expanded-valent vaccines were based on serology of the expanded-
valent vaccine compared with PCV72-4
• PCV7 and PCV13 are conjugated to CRM1973
• PCV10 is conjugated to a Haemophilus influenzae‒derived protein D, nontypeable
H influenzae carrier for all serotypes except 18C (tetanus toxoid) and 19F (diphtheria toxoid)2
DT=diphtheria toxoid; TT=tetanus toxoid.
1. Prevenar [summary of product characteristics]. Wyeth Lederle Vaccines. 2. Vesikari T, et al. Pediatr Infect Dis J. 2009;28(4 suppl):S66-S76. 3. Prevenar 13
[summary of product characteristics]. Pfizer Ltd. 4. World Health Organization. Recommendations for the production and control of pneumococcal conjugate
vaccines. WHO Technical Report Series, no. 927, 2005, Annex.
http://www.who.int/biologicals/publications/trs/areas/vaccines/pneumo/ANNEX%202%20PneumococcalP64-98.pdf. Accessed May 16, 2019. 18
PCV10 vs PCV13
• PCV13 contains pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A,
19F, and 23F.
• PCV10 contains ten of these serotypes (except serotypes 3, 6A, and 19A), although
there is evidence for some cross-protection against serotype 6A and 19A disease
Pneumococcal Conjugate
Vaccine
• Polysaccharide polysaccharide conjugated to nontoxic diphtheria toxin (7
serotypes)
• Vaccine serotypes account for 86% of bacteremia and 83% of meningitis among
children <6 years
• Highly immunogenic in infants and young children, including those with high
risk medical conditions
• >90% effective against invasive disease
• Less effective against pneumonia and acute otitis media
 France, PCV13 2+1

All-Cause CAP* Cases in Children 1 Month–15 Years

of Age and Children <2 Years of Age in 8 Pediatric Hospitals
CAP (children 1 month–15 years and <2 years of age)

2400 CAP 1 month–15 years

CAP <2 years

2000
16% reduction
Number of Cases

vs pre-PCV13
1600

1200

800
32% reduction
vs pre-PCV13
400

0
Pre-PCV13 Transition Post-PCV13
(June 2009–May 2010) (June 2010–May 2011) (June 2011–May 2012)
*X-ray confirmed.
CAP=community-acquired pneumonia.
Angoulvant F, et al. Clin Infect Dis. 2014;58(7):918-924. 21
 France, PCV13 2+1

Pneumococcal CAP*† Cases in Children

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

100
Number of Cases Pneumococcal CAP

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. 22
 US, PCV13 3+1

Incidence of Annual Visits for Otitis Media (OM) Among

Children <5 Years of Age

Post-PCV7 (2002–2009) Transition (2010–2011) Post-PCV13 (2012–2014)

1,2
Adjusted rate ratio* (95% CI)

1 22% 20%
23%
31%
0,8

0,6

0,4

0,2

0
Physician's office- Hospital ED Physician's office- Hospital ED
based visits based visits

Children <2 years of age Children 2–4 years of age

• The annual rates of OM-related visits decreased during the post-PCV13 period among children <5 years of age
(by 20.0%–31.0%) compared with the post-PCV7 period

*Rate ratio was adjusted for age, sex, race/ethnicity, and health insurance.
CI=confidence interval; ED=emergency department.
Kawai K, et al. J Pediatr. 2018. doi: 10.1016/j.jpeds.2018.05.047. [Epub ahead of print] 23
 US, PCV13 3+1

IPD Cases Due to Serotype 3 in Children

<5 Years of Age

PCV7
60 2000
PCV13 31% reduction
2010 (vs 2007–2010)
50
Number of Cases

40

30

20

10

0
2004–2007 2007–2010 2010–2013

Moore MR, et al. Lancet Infect Dis. 2015;15(3):301-309. 24

Pneumococcal NP Carriage in
Indonesia
Province Year Subject N % NP carriage Most Common Serotype

Lombok 1 1997 Children, 0-25 months 484 48 6, 23, 15, 33, 12, 19

Bandung 2 2004 Children, 0-8 weeks 108 13.9 No information

Semarang3 2010 Children, 6-60 months 243 43 6A/B, 15 B/C, 11A, 23F,19F

Lombok4 2012 Children, 2-60 months 1200 46

46- 60 %
6A/B, 19F, 23F, 15 B/C,19A

ra ge :
Jakarta5 2012 Children (HIV) 4-144 months
t y pe Cov90e 46 19F, 19A, 6A/B, 23F, 11A

Children, <513 S e ro
Gunung Kidul 6
2017
P C V years 1008 31.2 6A/6B, 19F, 3, 14, 23F

Sumba6 2017 Children, <5 years 814 84.5 6A/6B, 19F, 23F, 19A, 14

Bandung7,8,9 2015 Children, 2 -12 months 200 21.5 - 67.3 6B, 19F, 23F, and 15A

Bandung10,11,12,13,14 2016 Children 1 - 2 years 302 49.5 15B/C, 23F, NT2, 19F, and 6A

Nasopharyngeal Carriage in Under-five: 43% - 55%

 Vaccination Schedule
Dose 1 Dose 2 Dose 3 Dose 4
2 Months 4 Months 6 Months 12–15 Months

Age Dose

7–11 3 doses, 4-8 weeks interval between doses, third dose after 1 year
Months of age, or minimal 2 months after second dose

12–23 2 doses, minimal 2 months after first dose

Months

>24 1 dose, can be given until 5 years of age

Months

Satgas Imunisasi IDAI. Pedoman Imunisasi Di Indonesia. Badan Penerbit IDAI. 2017: 297-308.
Jadwal Imunisasi Kemenkes
https://www.kemkes.go.id/resources/download/info-
terkini/BUKU%20KIA%2020_03%202016.pdf
 PCV Demonstration Program in Indonesia
Central, North Lombok and Mataram
Launching of PCV Immunization Bangka, Central Bangka, Pangkal
West and East Lombok Pinang November 2018
Vaccine: PCV13
Time: October 2017

Syamsu Alam. Learning and Sharing Experience on PCV Demonstration Program in Indonesia. Presented in 16th Asia Pasific Congress of
Pediatrics, Bali Nusa Dua Convention Center, 27 August 2018
Invasive Pneumococcal
Disease: Incidence by Age Group
250

200

150
Rate

100

50

0
<1 1 2 3 4 5-17 18-34 35-49 50-64 65+
Age Group (Yrs)
Pneumococcal Vaccines Adverse
Reactions
Reactions Type Rate
Local Reactions Polysaccharides 30-50%
Conjugate 10-20%
Fever, Myalgias Polysaccharides <1%
Conjugate 15-24%
Severe Adverse Very Low Very Low
Reactions
Pneumococcal Vaccines
Contraindications and Precautions
•Severe allergy to vaccine component or following prior dose of
vaccine
•Moderate to severe acute illness
Jadwal Imunisasi IDAI 2017
• 5. Vaksin pneumokokus (PCV). Apabila di berikan pada usia 7-12 bulan, PCV
diberikan 2 kali dengan interval 2 bulan; dan pada usia lebih dari 1 tahun diberikan
1 kali. Keduanya perlu booster pada usia lebih dari 12 bulan, atau minimal 2 bulan
setelah dosis terakhir. Pada anak usia diatas 2 tahun PCV diberikan cukup satu kali
Take Home Message
• Pneumococcal infection is a vaccine-preventable disease with high
morbidity and mortality
• PCV vaccine is can effectively lower the burden of this diseases, invasive or
non-invasive
• Study in Indonesia showed that nasopharyngeal carriage contains
serotypes that match from the PCV vaccines
• Indonesia Pediatric Society scheduled PCV given 3 primary doses (age
2.4.6 mo) with 1 booster dose (12 mo)
• Indonesian National Health Program started to give in Lombok in 2017,
and will be nationwide in 2024
 TERIMA
KASIH
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