3/5/2018

Fever and rash again:

Measles in infants and
Congenital Rubella Syndrome,
2017 report

Dwiyanti Puspitasari

PIDW, 24-25 Februari 2018

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Outline
• Introduction
• Measles, what is new in 2017?
• Congenital Rubella Syndrome/ infection (CRS/I)
• CRS surveillance report 2017
• Take home message

INTRODUCTION
• Measles and Rubella are acute infections, very
contagious, high reproductive rate (R0)
Diseases R0 Herd immunity
Diphtheria 6-7 85%
Measles 12-18 83-94%
Mumps 4-7 75-86%
Pertussis 12-17 92-94%
Polio 5-7 80-86%
Rubella 6-7 83-85%
Smallpox 5-7 80-85%
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Michigan center of public health preparedness,2018

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MEASLES RUBELLA ELIMINATION PROGRAM, 2000-2020

Reported measles incidence rate, per country,2016

MEASLES RUBELLA ELIMINATION PROGRAM, 2000-2020

Reported measles incidence rate, per country,2016

• WHO SEARO regional target on MR control/

elimination: control measles and rubella/CRS
by 2020
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GOOD NEWS
• The western hemisphere eliminated measles
in 2002 and rubella in 2009
• Measles deaths fell by 84% between 2000 and
2016 (fewer than 100,000 for the first time!!)
• Rubella containing vaccines implemented in
17 new countries during 2012 – 2015 (72%
countries by the end of 2016)

NOT GOOD NEWS…..

Countries with highest number of measles case in the world,2016

Indonesia in 6th rank 8
Source: Global MR Initiative.org

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NOT GOOD NEWS…..

MR vaccine introduction in Indonesia (2017 -2018): Java

island :first round campaign in Aug/ Sept 2017

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Outline
• Introduction
• Measles, what is new in 2017?
• Congenital Rubella Syndrome/ infection (CRS/I)
• CRS surveillance report 2017
• Take home message

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Measles among infants < 9 months

Increasing number of <6mos infants

Contracting measles
unimmunized
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Epidemiology of measles in infants younger than 6 months: analysis of surveillance data 2011- 2016, WHO, CDC, 2017

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WHO recommendation (2015):

• Countries with burden of measles in <1 yr old
infants:
– High : measles immunization at 9 mos
– Low : measles immunization at 12-15 mos
• Primary immunization given in 2 doses as
measles/ measles rubella
• If measles vaccine given in infants <6 mos,
counted as additional dose (MCV0)
• Can be given in HIV child without signs of severe
immunodeficiency: reduced maternal antibody
transfer
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PLOS ONE | DOI:10.1371/journal.pone.0169713 January 11, 2017

• measles vaccine decreased risk of diarrhea, reduction in ARI by

15–30 percent in India and Pakistan, and diarrhea cases by 12–22
percent in Congo, India, Nigeria and Pakistan
• early measles vaccination was associated with reductions in
diarrhea (HR: 0.89), vomiting (HR, 0.86), and fever (HR, 0.93)
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Published: 11 January 2017

Meta-analysis from 5 RCT, over 5,000 children

Earlier vaccination (≤12 vs ≥15 months), antibody
responses reduced. It persisted after the second dose

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WHO, CDC systematic review in Sept 2017:

Humoral immunity after MCV1<6 mos of age, depend
on: age of MCV1, presence of maternal antibodies, strain
used.
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Lochlainn N, Hahne LS. 2017 MCV: measles containing vaccine

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Measles in developed countries with MR

elimination, new issues arised:
• Decresed measles Ab titer in immunoglobulin I.V.
 below required threshold, even after booster
• Maternal antibody in infants wean faster than those
with natural infection
• Increased risk of SSPE, especially in:
• Male
• Contracted measles <15 mos (before vaccination)
• Median age on diagnosis: 12 (3-35) years
• Latency period: 9.5 (2.5-34) years
Measles vaccine should be given earlier
if there is increased risk to measles exposure
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Modrof 2017, Wendorf 2017

Outline
• Introduction
• Measles, what is new in 2017?
• Congenital Rubella Syndrome/ infection (CRS/I)
• CRS surveillance report 2017
• Take home message

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Congenital Rubella
Syndrome / Infection
• Congenital Rubella Syndrome (CRS):
variable constellations of birth defects
associated with intrauterine rubella infection
(eg, hearing impairment, heart defects, cataracts/
glaucoma/pigmentary retinopathy)

• Congenital Rubella Infection (CRI):

all outcomes associated with intrauterine
rubella infection (eg, miscarriage, stillbirth,
combinations of birth defects, asymptomatic infection)
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Clinical Manifestation after CRI

• CRI is a persistent infection, not like in acquired

Rubella infection
• Wide variation of clinical manifestation, depend on
the age of maternal Rubella infection
• Clinical manifestation :
 permanent
 transient
 late manifestation
• Most of clinical manifestation will present within
first 5-8 years of life

 Short term and long term follow up is important 20

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Rubella in a Pregnant Woman

• Before 12 weeks pregnancy up to 90% risk of:
- Miscarriage - Cataracts or retinopathy
- Cardiac anomalies - Nerve deafness
- Mental retardation - Often multiple defect
• Fetus somewhat safer in the 2nd trimester but…
Sensory neural deafness is the most common problem
• In the second half of pregnancy,
• Hepato-splenomegaly
• Failure to thrive, osteitis
• Diabetes, hypothyroidism and GH deficiency
• Progressive panencephalitis
= The Congenital Rubella Syndrome
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CONGENITAL DEFECT & LATE MANIFESTATION OF CRI

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!

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Outline
• Introduction
• Measles, what is new in 2017?
• Congenital Rubella Syndrome/ infection (CRS/I)
• Indonesia CRS surveillance report 2017
• Take home message

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CRS Surveillance Indonesia

• Hospital based surveillance was conducted in 13
referral hospital across Indonesia, started in 2015
• Target screened: infant <1th with at 1 symptom
(CHD, hearing loss, cataract, glaucoma, retinopathy pigmentary)
• Goal: suspect, clinical & laboratory confirmed CRS
• Serology confirmatory examination performed in
Measles-Rubella national reference laboratory

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CRS Clinical Case Definition

CRS suspect: infant <1 yr with:
• Minimal 1 symptom in group A
CRS Symptoms
Clinical CRS : infant <1 yr with:
Group A
• 2 symptoms in group A; or
• 1 symptom in group A + 1 in B • Hearing loss
Confirm CRS : CRS Suspect + Lab. • Congenital Heart Disease
• Congenital cataract
• If infant <6 mos: Rubella IgM (+) • Congenital glaucoma
• If infant 6 mos - <1 yr: • Retinopathy pigmentary
Rubella IgM and IgG (+); or Group B
2 time IgG (+) (with 1 mo interval)
• Purpura
Confirmed in WHO accredited Measles-
• Splenomegaly
Rubella reference laboratory • Microcephaly
• Mental retardation
Discarded CRS : • Meningoencephalitis
CRS suspect whodidnt fulfilled clinical • Radiolucent bone
& confirmed CRS criteria • Icteric within first 24hrs 26

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CRS Surveillance Flow in hospital

CRS Suspect

1. Fill Form CRS1 PEDIATRIC

COMPLETE
2. Hosp.Lab  take Consult AUDIOLOGY form CRS1
1 cc blood
OPTHALMOLOGY
3. Consult to other
2 Dept.
CRS COORDINATOR
CHECK DATA COMPLETENESS

CRS DATA COORDINATOR

CHECK DATA COMPLETENESS
Input Data in Web PD3I
Province
Koordinasi Coordinator
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Send spesimen to Measles-Rubela National lab.

Monthly Suspect CRS cases web-based report

2016 - 2017

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Classification of CRS Cases (Percentage)

2015 - 2017

Confirmed CRS
Clinical CRS
CRI
Discarded
Pending

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*Data 2015 is final data

Clinical Finding in Clinical & Lab-confirmed CRS (Aggregate)

2015 - 2017
Total clinical and Lab confirmed CRS
2015 : 96 cases
2016 : 177 cases
2017 : 27 cases

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*Data 2015 is final data

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Multiple Mayor Syndrome in Clinical and Lab-confirmed CRS (Percentage)

2015 - 2017

Total clinical and Lab confirmed CRS

2015 : 96 cases
2016 : 177 cases
2017 : 27 cases

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*Data 2015 is final data

Age Distribution in Lab-confirmed CRS

2015 - 2017
Total Lab confirmed CRS cases
2015 : 36 cases
2016 : 65 cases
2017 : 16 cases

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*Data 2015 is final data

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Mother Age Distribution in

Clinical and Lab-confirmed CRS
2015 - 2017
Total clinical and Lab confirmed CRS Total Lab confirmed CRS cases
2015 : 96 cases 2015 : 36 cases
2016 : 177 cases 2016 : 65 cases
Upto June 2017 : 27 cases Upto june 2017 : 16 cases

JUST THE TIP OF THE ICEBERG!!

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*Data 2015 is final data

Challenge in CRS Management

1. To diagnosed hearing loss, congenital eye
defect, CHD in infants need specialized facility
only available in tertiary referral hospital
2. Management (CHD correction, cataract
surgery, hearing aid/ cochlear implant, rehab)
are expensive, not fully covered by national
insurance
3. Longlife sequele persist despite early diagnosis
& treatment
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Challenge of CRS nation wide prevention

• CRS is preventable!
– Two doses of Rubella vaccine give nearly 100%
protection against Rubella
• WHO SEARO goal towards Rubella/ CRS control
by 2020:
– introduction MR vaccine campaign in Indonesia:
• Aug 2017: Java: overall coverage >96% of 36 million child
• More challenging introduction campaign in 2018

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Take Home Messages

• Measles and rubella are preventable, but high
vaccine coverage needed
• Measles Rubella elimination goal in 2020,
likely not achieved: we need to move faster!!:
– Two primary infection of MR
– Supplementary immunization in school age
– Strengthening CRS and measles surveillance

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……among the real challenge

of CRS nation wide
prevention with
MR vaccine campaign

T HA N K Y O U
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