1.

Measles
a. Measles virus
b. Measles disease and epidemiology
2. Rubella
a. Rubella virus
b. Rubella/CRS disease and epidemiology
3. Summary
• RNA virus

• Family: Paramyxoviridae

• Genus: Morbillivirus

• Humans are the only reservoir

• Transmitted via respiratory secretions or aerosols

• Multiplies in the respiratory tract

• 24 known genotypes, geographically

representative
 Of 24 known genotypes, only
6 were detected in 2013

Data source: MeaNS Database
Updated on 03 February 2014
Not applicable
The boundaries and names shown and the designations used on this map do not imply
the expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or
concerning the delimitation of its frontiers or boundaries. Dotted lines on maps
represent approximate border lines for which there may not yet be full agreement.
©WHO 2014. All rights reserved.
An acute disease

• Highly infectious: nearly everyone exposed gets the disease

if not immune (R0 = 12-18)*

• Incubation period: 8-15 days (rash to rash interval 7-21 days)

• Cases are infectious from 4 days before to 4 days after rash

onset

• Mortality highest in children <1 yr and adults

R0 = basic reproduction number = number of secondary cases

infected from a primary case in the absence of immunization
 • Fever

• Maculopapular rash

• The 3Cs:

 Cough

 Coryza (runny nose)

 Conjunctivitis (red eyes)

Photo courtesy of Professor Samuel Katz,

Duke University Medical Center.
- Prodrome: lasts 2-4 days
 Fever (daily increase in temperature), cough, coryza,
conjunctivitis
 Koplik spots: small white spots in buccal mucosa -
pathognomonic
 Period of greatest infectiousness (virus shedding)
- Rash begins: 2-4 days after prodrome starts
- Starts on face, head, neck, spreads down and out to
extremities
- Disappears in ~8 days, in same order as it appeared
- Case remains infectious from 4 days before to 4 days after
rash onset
 Clinical Course of Measles

Incubation period Prodrome Rash

( 7–21 days before rash) (about 4 days) (about 4–8 days)

-21-20
-19-18-17-16-15-14-13-12-11-10 -9 -8 -7 -6 -5 -4 -3 -2 -1 0 1 2 3 4 5 6 7 8

4 days after
Rash
21 days before 4 days before rash onset
rash rash onset Is the probable
Earliest possible Is the probable start end of
exposure of infectiousness infectiousness
The case is
identified here
 Any disease or death not clearly due to another cause
(e.g., trauma) during the 30 days following rash onset

 Occur mostly in 2nd and 3rd weeks

 Usually otitis media, diarrhea, pneumonia, less common

keratitis, and death

 Case Fatality Ratio (CFR) 0.1 – 10 % (up to 30% in humanitarian

emergencies)
 Corneal scarring
causing blindness
Vitamin A Deficiency

Encephalitis
Older children, adults
Chronic disability
~ 0.1% of cases

Desquamation: occurs on skin,
respiratory and gastro-intestinal tract
Pneumonia &
diarrhea
Diarrhea common in developing countries
Pneumonia occurs in ~ 5-10% of cases,
usually bacterial super-infection, major
cause of death
Sub-acute Sclerosing Panencephalitis (SSPE)

- Delayed complication: average 7 years after measles

infection

- Rare (1 in 100,000 cases)

- Degenerative CNS disorder with personality changes,

seizures, motor disability, progressing to coma and death
 Age (infants, adults)

 Poor nutritional status

 Vitamin A deficiency

 Cellular immunodeficiency (e.g., HIV, cancer/cancer treatment)

 Measles Epidemiology
Pre-vaccine and Vaccination Era
Pre-vaccine or low High vaccination
coverage coverage
- Large, frequent outbreaks (q2–4y)
- Smaller and less frequent outbreaks
8000 - Most cases are unvaccinated
- More cases in infants, older children
100%

7000
- Most cases are <5 years old
and (young) adults 90%
-1-2 y in AFR
- More cases in vaccinated persons 80%
6000 -5-6 y in US, EUR
70%
5000 By adulthood, natural protection

Coverage
-
60%
Cases

4000 50%

3000 40%
30%
2000
20%
1000 10%
0 0%

Measles Cases Measles Coverage

 Disease Transmission R0*
Measles Airborne 12 - 18

Pertussis Airborne 12 - 17

Rubella Airborne 6-7

Diphtheria Saliva 6-7

Mumps Airborne 4-7

Polio Fecal Oral route 5-7

*Basic reproduction number: the average number of

secondary cases that are produced by a single index case
in completely susceptible population.
Herd Immunity - Scenario I
Immune Susceptible Contagious

Low population immunity

Chance for contagious to meet susceptible is high

Disease spreads fast. Transmission is
sustained. Outbreaks are frequent
 Herd Immunity - Scenario II
Immune Susceptible Contagious

High population immunity

Above a certain threshold of population immunity (e.g., 95% for
measles), chance for contagious to come into contact with
susceptible is low
Disease spread is limited. Outbreaks are small. This population has
herd immunity
 Herd Immunity Thresholds
 Herd immunity threshold (H) = the population
immunity required for incidence to decline

 H = 1 – 1/R0 Population
Immunity

 Measles: H = 1 - 1/18 = 1 - .056 = 94.4%

H = 1 – 1/12 = 1 - .083 = 91.7%
Required vaccination coverage: ~95%
 Rubella: H = 1 – 1/7 = 1 - .143 = 81.7%
H = 1 – 1/6 = 1 - .167 = 83.3%
Required vaccination coverage: ~85%
• Togavirus (RNA virus)

• 13 genotypes reported

• Respiratory transmission of virus or droplets

• Incubation period longer than measles: 12 – 23 days (Avg 14

d)

• Humans are the only reservoir

 Distribution of Rubella Genotypes
from Jan to Dec 2013

Not applicable

Data source: RubeNS Database
Updated on 03 February 2014
The boundaries and names shown and the designations used on this map do not imply
the expression of any opinion whatsoever on the part of the World Health Organization
concerning the legal status of any country, territory, city or area or of its authorities, or
concerning the delimitation of its frontiers or boundaries. Dotted lines on maps
represent approximate border lines for which there may not yet be full agreement.
©WHO 2014. All rights reserved.
• Symptoms/signs: Maculo-papular rash,
low grade fever, conjunctivitis,
lymphadenopathy, arthralgia/arthritis
NB: no cough

• 20-50% of infections are without rash or

asymptomatic
Rash

 Maculopapular (that
does not coalesce)

 Milder than measles

rash

 Begins on face and

head and spreads
downward
• Other symptoms

 Conjunctivitis
 Lymphadenopathy:
post-auricular, posterior
cervical, and sub-
occipital
 More common in
children than adults

 Arthralgia or arthritis
 Children and men: rare

 Women: up to 70%
 Rubella - Complications
• Thrombocytopenic purpura

 1/3,000 cases

• Encephalitis

 1/6,000 cases

• Progressive rubella panencephalitis (PRP)

 Extremely rare-20 cases identified since 1974

 Usually occurs 6 months – 4 years after primary

infection or birth (in CRS); most cases 8-19 years old

• Congenital rubella syndrome (CRS) among newborn

children of mothers infected during pregnancy
• Infection may cause
fetal death, premature
delivery and/or
congenital defects

• Infection during first

trimester carries
highest risk of CRS
(hearing impairment
may occur through
week 20)

• Organ specificity
generally related to Thrombocytopenic Purpura,
AKA “Blueberry Muffin Baby”
stage of gestational
• Sensorineural hearing Impairment

• Cataracts, glaucoma, pigmentary retinopathy

• Heart defects (particularly Patent Ductus Arteriosus and

Primary Pulmonic Stenosis)

• Purpura

• Microcephaly

• Developmental Delay

• Bone alterations

• Liver and spleen damage

 70
Percentage of CRS cases

60
50 Triad
40 CAT
CHD
30
HI
20 Single
10
0
HI CHD CAT
Defects
• May be infectious for one year
• Considered non-infectious after two negative cultures
at least one month apart after 3 months of age
• Maintain contact isolation/precautions for non-immune persons
• Estimated 103,000 cases of CRS born worldwide in 2010

- all in Eastern hemisphere

• Rubella eliminated in the Western hemisphere

− Last case reported from Argentina in 2009

• Rubella is not as infectious as measles: R0 = 6-7 vs. 12-18

• Usual inter-epidemic interval: 5-9 years (in absence of

vaccination)
- Children most commonly affected

- Infected women of child bearing age of greatest concern

because of CRS risk if pregnant

- Single dose of rubella vaccine as early as 9 months of age

protects 95% (greater than herd immunity threshold)

- Rubella/CRS elimination goal achievable by targeting

children and adolescents through existing measles
elimination strategies

- Women of child bearing age also should be vaccinated to

provide current and direct protection
Characteristic Measles Rubella
s
Pathogen/Family RNA Virus –Paramyxovirus RNA Virus - Togavirus

Infectiousness R0 – 12-18; highly infectious R0 - 6-7; highly infectious

Incubation period 7-21 days 12-23 days

(rash to rash)
Infectious period 4d before to 4d after rash 7d before to 5 d after rash;
CRS up to 12 m after birth
Complications Pneumonia, diarrhea, otitis Thrombocytopenic purpura;
media, corneal scarring; encephalitis, CRS
encephalitis;
Timing of Most complications occur during Infection early in pregnancy
Complications 2nd and 3rd weeks after rash can lead to severe birth
defects in newborns
High risk groups Infants and adults at highest risk Susceptible pregnant
of complications and death women
Doses of vaccine 2 doses At least 1 dose
needed
Thank You
 Vaccine (buku – good reference for Ro)
 Lihat bab: Community (bagaimana hitung herd immunity threshold –
untuk memotong transmisi)
 Ro (ada basic dan effective) – lihat buku
 Can give immunoglobulin at time of exposure (but once baby
has rubella, there is no intervention/Rx)
 IgG cut-offs depend on the test kit used (labs base it also on
pos/neg control).
 For babies infected (CRS born) who are infectious for up to one
year:
 Vaccinate contacts and isolate affected baby
 Different ways to protect contacts
 Need to isolate the infectious baby if hospitalized
 Regular rubella vaccine doesn’t work in CRS babies because their
immune system is affected by the disease (but nasal-administered
vaccine seems to work: babies seroconvert)