Introduction to Measles

Epidemiology, Clinical
Management, Surveillance, and
Outbreak Risk Assessment

May 10, 2023

Christopher Hsu, MD, PhD, MPH

Katrina Kretsinger, MD, MA
U.S. Centers for Disease Control and Prevention
 Outline

1. Biology, clinical presentation and transmission

2. Measles surveillance
3. Diagnostic testing
4. Outbreak detection and response
5. Regional and national measles data
Measles Virus (MeV) Characteristics

• RNA virus
• Family: Paramyxoviridae
• Genus: Morbillivirus
• Humans are the only reservoir
• Multiplies in the respiratory tract
• 24 known genotypes

Source: https://asm.org/Articles/2019/May/Measles-and-
Immune-Amnesia
Disease Characteristics
• Prodrome: lasts 2-4 days Coryza Rash
• Fever
• Cough
• Coryza
• Conjunctivitis
• Koplik spots
Conjunctivitis
Koplik spots
• Rash details
• Starts on face, head, neck,
spreads down and out to
extremities
• Maculopapular, non-vesicular
• Disappears in ~8 days, in same
order as it appeared
Natural History

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

Infectiousness Rash Infectiousness

starts ends
Exposure

The case is
identified here
Infectiousness
• Basic reproduction number (RO):
• the average number of secondary cases that are produced by a single index
case in a completely susceptible population
• determines level of population immunity needed to stop transmission
• Nearly everyone exposed to measles virus gets the disease if not
immune

Population Immunity Needed

Disease Transmission R0 to Stop Transmission

Measles Airborne/Aerosol 12 – 18 92-94%

Pertussis Airborne/Droplet 12 – 17 92-94%
Rubella Airborne 6–7 83-86%
Diphtheria Saliva 6–7 83-86%
Polio Fecal-Oral route 5–7 80-86%
Mumps Airborne 4–7 75-86%
Measles Complications
• Definition: any disease or • Persons at higher risk for
death not clearly due to
another cause (e.g., trauma)
during the 30 days following
rash onset
• Occur in ~1/3 of patients,
typically 2-3 weeks after
infection
• Most common: otitis
media, pneumonia,
diarrhea
• Less common but severe:
blindness, encephalitis,
death
complications
• Children < 5 years especially
infants!
• Adults (elderly)
• Persons with vitamin A
deficiency/malnourished
• Persons with congenital or
acquired cellular immune
deficiencies
• Pregnant women
• Fetal health
 Treatments
• Analgesics
• Fluids
• Post-exposure vaccination
• People without immunity to
measles
• Within 72 hours of exposure to
the measles virus
• Immune serum globulin
• Given within 6 days of
exposure to pregnant women,
infants and people with
weakened immune systems to
reduce disease severity
• Antibiotics
• Bacterial co-infection (e.g.,
pneumonia or an ear infection)
• Vitamin A
• All measles patients (children
and adults) receive vitamin A
• Two doses 24 hrs apart:
50,000 IU if <6 months
100,000 IU if 6-11 months
200,000 IU if >12 months
• If Vit A def (e.g., ocular
involvement):
Additional 3rd age-appropriate
dose 2 weeks after two initial
doses
Measles Immunization Service Delivery

• Routine immunization (RI)

• 2 doses measles-containing vaccine (MCV1, MCV2)
• Age of administration varies by country
• Vaccine is often combined with rubella, mumps and/or varicella
• Supplemental Immunization Activities (SIA) of two general types
• Initial catch-up SIA: all children aged 9 months–14 years to
eliminate susceptibility to measles in general population
• Periodic follow-up SIAs: all children born since the last SIA to
eliminate any measles susceptibility that has developed in
recent birth cohorts and to protect children who did not
respond to MCV1
• Outbreak response immunization (ORI)
 Aggregate vs. Case-Based Surveillance

• Aggregate
• A summary count of cases, by time or geographic area
• Example: Districts reporting the number of cases of
measles in January
• Case-based
• Collection and analysis of data from individual cases
• A case investigation form is completed for each case
• In the database or line listing, each record represents a
case with clinical and lab data
• Data collected are similar to those in an outbreak
investigation
 Measles Surveillance,
by Phase of Prevention
Outbreak
Control Elimination
Prevention

• Type: case-based for

outbreaks only; blood • Type: case-based;
• Type: Aggregate from initial 5 cases only blood from all unless
8000 epi-linked; throat swab
100%
• Data: # of clinical • Data: # of cases by or urine for genotype 90%
7000 cases age group, vax status
80%
• Data: 12 core variables
6000
• Analysis: incidence • Analysis: age specific 70%

5000 by time, place incidence; cases by age • Analysis: extensive +

60%
group, vax status performance indicators
•Purpose: monitor 50%
Cases

4000

Coverage
incidence; ID high •Purpose: describe • Purpose: classify cases;
40%
3000
risk areas changing epidemiology; customize interventions;
30%
2000
predict outbreaks; ID virus; verify elimination
ID high risk populations 20%

1000 10%

0 0%
Control Outbreak prevention Elimination

Measles Cases Measles Coverage

 12 Core Variable Data for
Adequate Investigation
➢ Personal identifier ➢ Date last vaccinated
➢ Place of residence ➢ Date of rash onset
➢ Place infected ➢ Date of notification
➢ Age or DOB ➢ Date of investigation
➢ Sex ➢ Date of specimen
➢ Travel history collection*
➢ Vaccination status

* not needed if epidemiologically linked

Source:
World Health Organization. Framework for verifying elimination of measles and rubella. Weekly Epidemiol Rec 2013;
88:89-98
 Measles Case Definitions
1) Clinical case definition:
(High) fever & (maculopapular) rash
AND
cough and/or conjunctivitis and/or coryza (3Cs)

2) Surveillance case definition (suspected case):

⚫ Varies by country
• Fever & rash only (to include rubella)
• Clinical case as above
• Suspected by clinician
 Differential Diagnosis of Fever and Rash

Measles Rubella
Dengue Other viral exanthemas

Scarlet fever Kawasaki

Fever + Rash
Toxoplasmosis Meningococcemia

Roseola infantum/ Mononucleosis

exanthem subitum
(HHV6/HHV7) Erythema Others
infectiosum
(Parvo B19)
 Action Points for Suspected Measles
• Immediately report case to surveillance officer;
investigate within 48 hours
• Collect blood sample at first opportunity and
throat/nasopharyngeal swabs to identify virus
genotype/molecular sequence (5-10 per outbreak)
• Complete case investigation form, conduct contact
tracing, search for additional cases
Blood Specimen Collection & Processing
1. Start Here

4. Storage

3. Centrifuge Clotted Blood

2. Leave at
room temp
for clot
formation

Centrifuge @ 1500 RPM – 10 Min

 Measles IgM and IgG Antibody Levels
after Infection or Vaccination
IgG: Rises steadily, plateaus
IgM: Rises rapidly, peaks, then
and remains high years after
decreases and disappears after
infection. In the case of
about 30 days; indicates acute
measles, indicates immunity
infection

Years after illness

- 14 -7 0 7 14 21 28 35
Days after onset

Rash Maximum amount of measles

onset IgM antibody: 4-28 days

- Lower sensitivity for IgM (70-80%) if specimen collected within the first 3 days
- Collect blood specimen at 1st contact; collect 2nd specimen if 1st specimen is
IgM negative and was collected within first 3 days after rash onset
 Alternative Specimen Collection Methods*
❑ Oral Fluid
⚫ Non-invasive; scrape gums with swab for at least 60

seconds; place in transport medium

⚫ IgM antibody detection and PCR (for genotyping)

possible
⚫ Requires reverse cold chain

⚫ May be less sensitive for IgG

❑ Dried blood spots

⚫ Must fill 3 circles with blood - usually from multiple finger

sticks;
⚫ Sensitivity in field is variable

⚫ PCR possible on blood spot but less sensitive

⚫ Easy storage and transportation (reverse cold chain not

required)
* MMWR June 20, 2008/57(24);657-660 ; http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5724a3.htm
 Collection of Throat Swabs for
Virus Detection

➢ Yield highest if collected

within 4 days after rash
onset
➢ Collect from up to 5 cases
during outbreak
➢ Transport to the lab at
4 – 8°C, using frozen ice
packs and appropriate
insulated shipping container
 Measles Case Classification
Confirmed
• Laboratory: measles IgM positive; 4-fold rise of measles
IgG in paired sera; PCR positive
• Epidemiologic linkage – clinical case linked in time and
place to lab-confirmed or other epi-linked case
Clinically confirmed or compatible
• Satisfies clinical case definition and
• no or inadequate specimen
• no identified epidemiologic linkage
Discarded
• IgM negative
• Confirmed as other disease
• Epi-linked to IgM negative case or other confirmed disease
 Classification of Measles & Rubella Cases
Measles Lab Confirmed*
Ig M + or Measles
PCR+
Adequate Rubella Ig M +
Specimen Rubella
or PCR +
Measles
Ig M -
Rubella Ig M -

Other confirmed
Suspected cause Discarded
Case
Epi-linked to confirmed
case of other
communicable disease
No/Inadequate or discarded measles
Specimen
Epi-linked to measles
or rubella; no other Epidemiologically
confirmed cause Confirmed

No other confirmed Clinically

disease Confirmed or
Compatible

* May also lab confirm by fourfold rise in IgG in paired sera or PCR+ Expert Review Committee?
 Measles-Rubella
Surveillance Performance Indicators
1. Proportion of reporting sites that report weekly (target: ≥ 80%)
2. Discarded measles (and rubella) cases per 100,000
population/ year at national level (target ≥ 2/100,000)
3. % of subnational units with ≥ 2 discarded measles (and
rubella) cases per 100,000 population/year (target: ≥ 80%)
4. % of suspected cases with adequate investigation* initiated
within 48 hours after notification (target: ≥ 80%)
5. % of suspected cases with adequate specimens collected and
tested in a proficient laboratory (target: ≥ 80%)
6. % of lab-confirmed outbreaks with adequate samples for virus
detection (target: ≥ 80%)
7. % of specimens that arrive to the lab within 5 days of collection
(target: ≥ 80%)
8. % of lab results reported within 4 days of specimen receipt in
lab (target: ≥ 80%)
 Traditional Outbreak Definition
❑ Number of cases observed > number of cases expected
⚫ in same geographic area

⚫ during same period of time

Greater than expected

11 2 33 4 Years 5
Measles Outbreak Definitions in Context
of Measles Elimination

“ … a single laboratory-confirmed measles case is

considered to be a confirmed measles outbreak.”

World Health Organization. Framework for verifying elimination of measles and rubella.
Weekly Epidemiol Rec 2013; 88:89-98
Measles Outbreak Definitions in Regions
with 2020 Elimination Goals

❑ AFR Measles Surveillance Guidelines

⚫ 5 or more suspected cases in a health facility or district in
one month
⚫ 3 or more lab-confirmed cases in a health facility or district
in one month

❑ SEAR Measles Surveillance Guidelines

⚫ Suspected outbreak: 5 or more suspected cases per
100,000 pop per month in a geographic area
(block/district)
⚫ Confirmed outbreak: 3 or more confirmed cases (of which
at least 2 are IgM+) in a health facility, block or district
(catchment area population 100,000)
 Causes of Measles Outbreaks
• Failure to vaccinate: large # of unvaccinated people
• Low routine coverage
• Low campaign coverage (<95%)
• Vaccine failure: vaccine did not work
• Expected (up to 15% primary vaccine failure when vaccine is
given @ 9 months – i.e., 85% VE)
• Unexpected (e.g. cold chain problems, poor quality vaccine,
etc.)
• Contributing factors:
• Policy or schedule failure
• Wrong age group targeted during SIA
• Missed birth cohorts (complicated SIA schedule)
• Long interval between MCV1 and MCV2 (e.g., administered at 7y)
• Migration
• Massive influx of susceptible populations
• Importation of cases
• Other
• Children born to HIV+ women
 Investigation of Measles Outbreaks
To determine nature of response, need to determine:
• Extent of transmission and contact tracing (before and after rash
onset in the case)
• How long? (duration of transmission, # of generations)
• How many? (# cases: total and in each generation of transmission)
• How far? (# and location of affected villages, districts, provinces)
• Source of infection
• imported, import-related, endemic, or unknown
• Epidemiology:
• ages affected; vaccination status; travel; occupation
• Population immunity in affected and surrounding areas
• Surveillance quality in affected and surrounding areas
• Response capacity
• vaccine, logistics, cold chain, staff, training, transport for possible ORI
• Vit A, antibiotics, ORS for case management
 Measles Case/Outbreak Detection & Response
Suspected/reported outbreak:
Rumors/Unverified
Isolate suspected cases and contacts in
notifications of “a measles
their homes; Activate outbreak response
case/outbreak”
team at each level;

Collect specimen (serum) for serological confirmation

(IgM) and throat swabs for virus detection
from at least 5 cases meeting case definition

No sample IgM+ 1-3/5 (<80%) samples IgM+ 4-5/5 (≥ 80%) samples IgM+

A confirmed outbreak
Not an outbreak of • Continue sampling to confirm • No more current samples
measles cases by lab to know • Confirm other cases by
Continue case-based magnitude of outbreak epidemiologic linkage
surveillance
Contact Tracing in Measles/Rubella Outbreaks
❑ What is a contact?
• Associated in time and place
a. Same room while case is present and up to 2 hours afterwards
b. Same house, work place, school, church/mosque, village?
❑ Who infected case 7-21 days ago?
❑ determine source of virus, identify other cases and extent of transmission

❑ Who did case potentially infect from 4 days before to 4 days

after rash onset?
• Provide MCV (within 3 days of exposure) or Immunoglobulin (within 6 days
of exposure, if immunocompromised or <9m old) to
a. reduce morbidity and mortality
b. prevent and monitor spread
c. Quarantine and follow up until 21 days post exposure
 Additional Case Finding in
Measles/Rubella Outbreaks
❑ House to house search in affected village/area
❑ Include areas where the case traveled 4 days before to 4 days after rash
onset and 7-21 days before rash onset
❑ Register review and requests to clinicians in neighboring health
facilities and teachers in schools looking back 3 months;
❑ Intensify passive reporting
❑ More frequent zero reporting (at least weekly) from public and private health
facilities, clinics
❑ Initiate reporting from schools
❑ Establish/mobilize network of community-based key informants
❑ Intensify active surveillance
❑ Weekly visits to public and private health facilities/clinics, schools
❑ Communication & Social Mobilization
❑ Public announcements
❑ Engagement of civil society
 Communication Methods during Outbreaks

Communication methods
❑ Radio, TV, newspapers, websites, social media
❑ Posters, fliers
❑ Meetings with health staff, community, religious and political
leaders
❑ Presentations at markets, health centers, and schools

Informing journalists
❑ Inform journalists who is the spokesperson
❑ Provide official updates to journalists only through
spokesperson
 Surveillance & Outbreak Response:
Key Points
- High quality surveillance is needed to identify cases (and
virus), eliminate residual areas of transmission, and verify
measles and rubella elimination
- Standard indicators should be used to monitor surveillance
quality
- Outbreak investigations determine need and extent of ORI
and to better understand evolving measles epidemiology
and risks
- Lab confirmation, virus detection and determing source of
virus as imported, import-related or endemic/unknown are
critical parts of case and outbreak investigations
 Goals for the
Immunization Agenda 2030
▪ Protect children from morbidity and
mortality caused by measles
▪ Measles vaccine to be readily available to
all children in all global regions
▪ Accomplished through global efforts in
surveillance, diagnostics and
vaccinations
Thank You