APPOINTMENT

❑ Lecturer in pediatric infectious disease and tropical pediatrics Universitas

Indonesia
❑ Pediatric ID consultant in Cipto Mangunkusumo National Referral Hospital
❑ Pediatric ID consultant Universitas Indonesia Hospital

Dr. Nina Dwi Putri, Sp.A(K),
MScTropPaed
EDUCATION
❑ Master of tropical pediatric, Liverpool School of Tropical Medicine, United
Kingdom, 2018/19
❑ Executive fellowship in Pediatric Infectious Disease, The Children hospital at
Westmead, Sydney - 2018
❑ Pediatric ID consultant training, Universitas Indonesia, 2015-2017
❑ Clinical fellowship in infectious disease for outpatient parenteral antibiotic
therapy, Institute of Infectious Disease and Epidemiology, Communicable
Disease Center, Tan Tock Seng Hospital, Singapore - 2014
❑ Pediatric Residency Training, Universitas Indonesia, 2007 -2012
❑ Medical Doctor, Universitas Indonesia, 2000-2006

ORGANIZATION
❑ Secretary of Scientific Affair of Indonesia Pediatric Society, 2017-
❑ Secretary of COVID-19 task force of Indonesia Pediatric Society 2019-
❑ Head of book division of Indonesia Pediatric Society Publishing Unit, 2015-

AWARD
❑ Thomas Mark Award, UK
❑ Endeavour Award, Australia
❑ Asia Pacific Economic Cooperation Scholarship, Singapore
Disclosure
Global meningococcal initiative member
Outlines
• Microbiology & transmission
• Prevention strategies
• Epidemiology of IMD in Asia Pacific & Indonesia
• Meningococcal Vaccine
• Chemoprophylaxis
• Disease surveillance
Transmission
• Person-to-person transmission by close contact with respiratory
secretions of a person with meningococcal disease or asymptomatic
carriage of N. meningitidis
• 16 serogroups reported, 6 are responsible for invasive disease (A, B,
C, W135, X, Y)
• Increased risk in specific population groups: infants, adolescents,
those with asplenia or complement deficiencies, crowded living
conditions such as in college dormitories, public mass gathering
• Asymptomatic nasopharyngeal carriage is transient, affecting an
estimated 5%–10% of the population at any given time

Crum-Cianflone N, Sullivan E. Infect Dis Ther. 2016 Jun;5(2):89-112.

 Prevention

Immunization Targeted Active disease Public

Chemoprophylaxis surveillance education &
awareness
Meningococcal Vaccine
Available Vaccines
• Quadrivalent vaccines
• Polysaccharide: MPSV4 & PsACWY
• Conjugate:
• A quadrivalent meningococcal polysaccharide conjugate vaccine-diphtheria toxoid carrier (MenACWY-DT)
• A quadrivalent meningococcal polysaccharide conjugate vaccine-diphtheria toxoid carrier, CRM197 (MenACWY-CRM)
• A quadrivalent meningococcal polysaccharide conjugate vaccine-tetanus toxoid carrier (MenACWY-TT)

• Monovalent vaccines
• Meningococcal serogroup B vaccine (MenB-FHbp; MenB-4C)
• Meningococcal serogroup C conjugate vaccine
• Meningococcal serogroup A vaccines

• Other: the combination conjugate vaccine serogroups C and Y and Haemophilus influenzae type b
(HibMenCY)
 Polysaccharide Vaccines
Antibody
Polysaccharide production
Poor response
B-cell receptor
< 2 yo
IgG2
Differentiation

IgM

Depletion of B-cell
B cell memory reserve
Plasma cell

No production of
From Pollard AJ, et al. Nat Rev Immunol. 2009;9:213-220. memory B cells 9
 Conjugated Vaccines Antibody
production
Carrier Polysaccharide Polysaccharide-
protein specific
plasma cell
B cell receptor
Polysaccharide-
Processing of specific B cell IgG1
carrier protein and
IgG3
MHC
class II

CD40 CD80 or
CD86
CD40L CD28

Memory
TCR
response

T-cell help
Polysaccharide-specific
From Pollard AJ, et al. Nat Rev Immunol. 2009;9:213-220.
memory B cell
11
Meningococcal conjugate vaccines represent a significant advance compared
with plain polysaccharide vaccines

Polysaccharide vaccines T cell-independent

Antibody response of short duration

No production of memory B cells

Polysaccharide
B cell Plasma cells
vaccine

Conjugate vaccines T cell-dependent

Antibody response of long duration

T cells help produce memory B cells

Conjugate B cell B cell: CD4+ T cell Plasma cells

vaccine Memory B cells

Pollard AJ, et al. Nat Rev Immunol 2009; 9: 213–20

12
Comparison of polysaccharide and conjugate vaccines
Property Polysaccharide Conjugate
Immunogenicity Adults High High
Young Children Poor HIgh
Quality of Avidity Low High
Antibody Persistence Low/Med High
Bactericidal activity Low High
Response to a booster Poor High
Induction of hyporesponsiveness Yes No
Induction of immunological memory No Yes
Prevention of carriage No Yes
Contributes to herd effect No Yes
1Khatami & Pollard. Expert Rev Vaccines. 2010;9(3); 2Granoff. In: Vaccines. 6th ed. 2013: chapter 21.
Impacts of MenA Conjugate Vaccine in African Meningitis Belt

Trotter CL et al. Lancet Infect Dis. 2017 Aug;17(8):867-872.

 MenC Conjugate Vaccine in UK
Infants + catch-up campaign up to 18 years old since 1999-2000

97%

Trotter CL et al. Expert Rev Vaccines. 2009 Jul;8(7):851-61.

 Netherlands: MenC disease controlled in by
vaccination, with rising MenW disease
Start of the MenC conjugate
vaccination among 14 months old, plus
catch-up to 18 y/o

The Pediatric Infectious Disease Journal • Volume 25, Number 1, January 2006

• May 2018 : Replace MenC vaccination for 14 months old

with Men ACWY vaccination
• October 2018: Introduce Men ACWY vaccination for cohort
of 14 years old |
17
 Carriage and Disease
35

30
Global carriage rate 10
25

Incidence
% carriers

20

15
5
10

0 0
0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85 90 95 100
Age (y)
Parent du Chatelet et al., J Infect 74, 564 (Jun, 2017).
Delbos et al., Eur J Clin Microbiol Infect Dis 32, 1451 (Nov, 2013).
Caugant et al., J Clin Microbiol 32, 323 (Feb, 1994).
Christensen, et al., Lancet Infect Dis 10, 853 (Dec, 2010).
Impacts of MenA Conjugate Vaccine in Chad
~ 1.8M people aged 1-29 years in 3 areas vaccinated

risk of meningitis:
90.4%
MenA carriage:  98% No MenA case

Daugla DM. et al. Lancet 383, 40–47 (2014).

MenACWY vaccination and invasive meningococcal disease in the US

Implementation of MenACWY vaccination programs in adolescents in 2005*1 has decreased the

incidence of IMD caused by vaccine serogroups across the US (2006–2016)2–12

Serogroups C, W, and Y Serogroup B

0.5 0.5
5–17 years

Incidence per 100,000 population

Incidence per 100,000 population

11–17 years
0.44
0.45 0.45 18–34 years
18–22 years
0.4 0.4
0.37

0.35 0.35

0.3 0.3
0.27
0.23
0.25 0.25

0.24 0.19 0.2

0.2
0.15 0.15
0.14 0.14
0.15 0.15
0.11 0.1 0.1
0.09 0.09
0.06 0.08 0.1 0.08
0.1 0.06 0.05
0.01 0.03 0.04 0.04 0.03 0.04
0.03 0.04 0.05
0.05 0.07 0.03 0.03 0.02 0.02
0 0.02
0.02 0.05
0 0.02 0.03 0.01
0 0
0 0
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016
Year
Year

Increases in vaccination coverage were associated with decreases in IMD incidence rates.
IMD, invasive meningococcal disease; *Approved in the USA in 20051
1. Bilukha OO, et al. MMWR 2005; 54 (RR-7): 1–21; 2–12. CDC. ABC Surveillance Report 20
Emerging Infections Program Network Neisseria meningitidis, 2006–2016 [Mar 2019]. See notes for full citations
MenACWY-D induces significantly higher antibody titers in children when
compared with MPSV4
Immune responses by age groupa
6000
Children aged 2–5
and 6–10 years: 5483 ■ MenACWY-D
■ MPSV4
5000 MenACWY-D induces 4615

statistically significantly
4000
higher antibody
rSBA GMT

3246
responses compared
3000
with MPSV4 2445 2374

1859 1924
2000 1639
1557 1545
1342 1407
1249 1228 1322
1098
930
1000 698
570 543
239 310 334
158
0
A C W Y A C W Y A C W Y

Age 2–5 years1 6–10 years1 11–18 years2

aAntibody
titers 28 days post-vaccination
CI, confidence interval; GMT, geometric mean titer; rSBA, serum bactericidal assay using baby rabbit complement
1. Sanofi Pasteur. 603-02 clinical study report, 2004 (data on file); 2. Sanofi Pasteur. MTA-02 clinical study report, 2003 (data on file)
21
 MenACWY-D in children/adults: post-marketing study in the US

Children: 1421 recipients aged 2–10 years (2007–2010)

Infants/toddlers: 116 recipients, aged 9–23 months (2011–2014)
Large surveillance study conducted in >30,000 recipients, the majority aged 11–18
years (2005–2006)

Monitored all non-elective hospitalizations, emergency department

visits, and selected outcomes in the clinic setting* during the
6 months following vaccine administration

No unexpected or new safety concerns

identified

This study provides reassurance for administration of MeMenACWY-D in

children and adults during routine care
*Includes Bell’s palsy, seizure, neuritis, Guillain-Barré syndrome, encephalopathy, encephalitis, epilepsy, transverse myelitis, multiple sclerosis, hypersensitivity reactions, idiopathic thrombocytopenic
purpura, diabetes, arthritis, hemolytic anemia, and collagen-vascular disease 23
Hansen J, et al. Vaccine 2017; 35: 6879–84; Hansen J, et al. Vaccine 2018; 36: 2133–8
Safety in Asian Populations
Vietnam (9 mo to 55 yo)
• Similar frequencies of AE, as seen in other populations
• Most solicited reactions were mild or moderate (grade 1 or 2) in intensity;
almost all resolved within 3 days
• No increased reactogenicity was observed after the 2nd dose of the vaccine
in participants 9-23 months.
• Most frequent solicited reactions:
• Local: tenderness or pain
• Systemic: appetite loss (9-23 mo) and malaise (2-55 yo)

Phan CH et al. Pharmacoepidemiol Drug Saf. 2019;1–6.

Routine vs selected population
Epidemiology of IMD in Asia Pacific
Country Incidence of IMD
Philippines 0.02–0.1 cases/100,000 persons/year

Malaysia Limited data

Thailand 0.04 cases/100,000 persons in
2019.
Australia 1.1 cases/100,000 persons (2018)

1995–1996: N. meningitidis cause of

Indonesia meningitis in 16.7% of bacterially-
confirmed cases in children <5 years
1998–2002: N. meningitidis detected
in 17.6% of culture-positive
meningitis cases in children <2
years
Outbreak of 14 cases of
meningococcal meningitis with 6
deaths in 2000
Singapore ∼0.2 cases/per 100,000
persons/year
Myanmar five IMD outbreaks since 1990
Indonesia: Need more robust data…

PCR Based Testing

Recommended and
Preferable
Epidemiology of Meningitis in DKI Jakarta

Month 2019 2020

January 9 16
February 16 8
March 21 16
April 15 21
May 21 11
June 9 11
July 20 6
August 10 6
September 17 7
October 16
November 18
December 8
Total 180

https://surveilans-dinkesdki.net
Selected Populations
• Public mass gathering: hajj, military, camp
• Traveling: study abroad
• Functional or anatomical Asplenia
• Immunocompromised
• Complement deficiency
• HIV
• Microbiologist
 Outbreak of Meningitis of Hajj Pilgrims, 2000

Adapted from
R. Borrow 2018
Reference in slide notes
31
Mustapha MM et al. Vaccine 34 (2016) 1515–1523
Outbreak of Meningitis of Hajj Pilgrims, 2000
 Mandatory Vaccines
1. Yellow Fever Vaccine Yellow Fever Endemic Areas

2. Meningococcal Vaccine
3. Polio (type 2 - IPV) Vaccine

Meningitis Belt
 Meningococcal Vaccine

Travelers to the Kingdom of Saudi Arabia (KSA) for Umrah or Hajj are required
to provide documentation of quadrivalent vaccine at least 10 days and no
more than 3 years before arrival for polysaccharide vaccine and no more than
5 years before arrival for conjugate vaccine
https://www.moh.gov.sa/en/Hajj/Pages/HealthRegulations.aspx
 Trade Name Age of Vaccine Interval Since
Vaccine Dose Route Booster
(Manufacturer) Initiation First Dose
Meningococcal Menveo (GSK) 2 mo 0.5 mL IM 0,2,4,10 mo If at continued risk
(serogroups A,C, 7-23 mo 0.5 mL IM 0,3 mo (2nd dose
W, and Y) administered in 2nd
oligosacccharide year of life)
diphtheria CRM ≥2 y 0.5 mL IM 1 dose
conjugate vaccine
(MenACWY-CRM)

Meningococcal Menactra (Sanofi 9-23 mo 0.5 mL IM 0,3 mo If at continued risk

(serogroups A,C, Pasteur) ≥2y 0.5 mL IM 1 dose
W, and Y
polysaccharide
diphtheria toxoid
conjugate vaccine
(MenACWY-D)
Meningococcal Trumenba (Pfizer) 10-25 y 0.5 mL IM 0,1-2,6 mo or 0,6 None
serogroup B mo (depending on
vaccine (MenB- indication)
FHbp)
Meningococcal Bexsero (GSK) 10-25 y 0.5 mL IM 0, ≥1 mo None
serogroup B
vaccine (MenB-4C)

CDC Yellow Book 2020

US ACIP: concomitant administration of MenACWY-D
ACIP recommendations for concomitant administration of MenACWY-D
with other vaccines
In children aged 9–23 months

• Concomitant administration allowed in healthy children

• MenACWY-D should not be administered concomitantly with PCV13 in children with

asplenia; MenACWY-D should be administered ≥4 weeks after completion of all
PCV13 doses

In people aged 2–55 years

• Concomitant administration allowed, but preferably at different anatomic sites

ACIP, Advisory Committee on Immunization Practices
Cohn AC, et al. MMWR 2013; 62: 1–28
36
MenACWY-D can be used concomitantly with DTaP-IPV/Hib vaccine in
toddlers 15–18 months of age
DTaP-IPV/Hib is a diphtheria/tetanus toxoids/acellular pertussis adsorbed/inactivated poliovirus
and Haemophilus b conjugate (tetanus toxoid conjugate) pediatric vaccine

Co-administration of
MenACWY-D and DTaP-IPV/Hib
Non-inferiority of antibody responses (vs
either alone) to:
• Meningococcal serogroups A, C, W or Y
• Pertussis (PT, FHA, PRN) or pertactin
antigens
No safety concerns identified
Study NCT01659996
FHA, filamentous hemagglutinin; hSBA, serum bactericidal assay with human complement; PRN, pertactin; PT, pertussis toxoid
Sanofi Pasteur. MTA55 clinical study report. 2015 (data on file)
37
Meningococcal Vaccine Use in Outbreaks

• Both MenACWY, and MPSV4 recommended for use in control of outbreaks

caused by A, C, W, and Y
• HibMenCY-TT may be used for age-appropriate persons in outbreaks specifically
caused by C and Y
• Outbreak definition:
• at least 3 confirmed or probable primary cases of the same serogroup
• period of 3 months or less
• primary attack rate of more than 10 cases per 100,000 population

CDC Pink Book

Chemoprophylaxis
• ASAP, ideally less than 24 hours after identification of the index
patient
• >14 days after onset of illness in the index patient probably of limited
or no value
• Rifampin, Ciprofloxacin, and Ceftriaxone 90%-95% effective in
reducing nasopharyngeal carriage of N. meningitidis and are all
acceptable for chemoprophylaxis

CDC Pink Book

Close contacts
• Household members, child care centre contacts, and anyone directly
exposed to the patient’s oral secretions (e.g., through kissing, mouth-to-
mouth resuscitation during the 7 days before symptom onset
• Healthcare professional: endotracheal intubation, or endotracheal tube
management)
• For travellers: any passenger who had direct contact with respiratory
secretions from an index patient or for anyone seated directly next to an
index patient on a prolonged flight (i.e., one lasting more than 8 hours)
• Visitors from African Countries: Ciprofloxacin tablets (500 mg)
chemoprophylaxis, administered at port of entry to lower the rate of
carriers
Acknowledgement
• Prof. DR. Dr. Sri Rezeki S. Hadinegoro, SpA(K)

• Prof. DR. Dr. Hardiono D. Pusponegoro, SpA(K)

• Dr. Benget Saragih, MEpid

Thank You