1. Global Measles Control: Current Status and Implications for Measles Control in the United States
Amra Uzicanin, M.D., M.P.H.
Global Immunization Division
Centers for Disease Control and Prevention
Atlanta, GA

2. Outline Introduction Global measles mortality reduction
Measles disease and complications
Measles vaccine and control during the 20th century
Global measles mortality reduction
Goals
Progress
Experience with regional measles elimination efforts
Successes
Challenges
Implications for measles control in the United States
Conclusions

3. Measles Clinical features: Public health significance: Fever
Maculo-papular rash
Three “C”s:
Cough
Coryza (runny nose)
Conjunctivitis (pink eyes)
Public health significance:
Highly communicable
May cause complications, incl. permanent disability
CFR: 0.1 – 15%
Photo courtesy of Professor Samuel Katz,
Duke University Medical Center.

4. Measles Complications
MOST FREQUENT:
Otitis Media
Pneumonia
Diarrhea
Encephalitis
Corneal scarring causing blindness
Subacute Sclerosing Pan-Encephalitis (SSPE)

5. Global Measles Control: 20th Century
In pre-vaccine era, nearly universal childhood disease
135 million cases, > 6 million deaths annually (estimates)
Safe and effective vaccine licensed in the U.S. in 1963
From mid-1970s through Expanded Program on Immunization
Global disease burden declined but death toll remained high
1987: 1.9 million deaths (estimate)
2000: 733,000 deaths (estimate)
Remaining global mortality burden mostly in Africa and Asia
In 2000, 47 countries accounted for 94% of global mortality
In the pre-vaccine era, measles was nearly universal childhood disease and most people would have had the disease by the time they reach adult age. The consequences of the uncontrolled measles virus transmission were an estimated 135 million cases and over 6 million measles-related deaths annually.
The era of measles control started in the early 1960s. In the U.S., a live attenuated measles vaccine was licensed in 1963, and from the 1970s it became available throughout the world through the Expanded Program on Immunization.
Subsequently, global disease burden gradually declined, but the death toll still remained high. As recently as in 2000, measles was still causing an estimated 733,000 deaths annually, most of which were occurring in developing world. In fact, in 2000, just 47 countries in Africa and South-East Asia accounted for 94% of the global measles mortality burden.

6. Global Measles Mortality Reduction: A 21st Century Goal
Initial Goal: 50% reduction by 2005
Achieved ahead of time and under budget*
Current Goal: 90% reduction by 2010¶
Key Strategies:
Improve case management
Improve coverage with the 1st dose of measles vaccine
Offer 2nd opportunity for measles immunization
Strengthen disease surveillance
*Lancet, 2007 Jan 20;369(9557): ¶

7. Average 1-dose measles vaccination coverage among children aged 1 year (2000-2003)
<50% (10 countries or 5%)
50-79% (53 countries or 28%)
80-89% (40 countries or 21%)
>=90% (89 countries or 46%)
Source: WHO/UNICEF estimates, 2004
192 WHO Member States. Data as of September 2004
Date of slide: 7 October 2004
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 All rights reserved

8. 47 Priority Countries for Global Measles Mortality Reduction, 2000 and 2008
No 2nd opportunity for measles vaccination
Yes, 2nd opportunity available
Source: WHO and UNICEF, 2009.

9. Routine 1st Dose Measles Vaccination Coverage, by WHO Region, 2000 and 2008
83%
Source of data: WHO (MMWR 2009;58:1321-6).

10. Global Measles Mortality Estimates All Ages, 2000-2008*
High-low lines indicate uncertainty bounds
*Source of data: WHO (MMWR 2009;58:1321-6). Method described in Lancet 2007;369:

11. Estimated Measles Deaths, 2008*
Dots are randomly distributed in countries.
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 All rights reserved
*Source: WHO, 2009.

12. WHO Regions with Measles Elimination* Target Date, March 2010
2000
2010
2012
(2020)
*Defined as interruption of indigenous virus transmission as a result of vaccination.

13. Vaccination Coverage and Reported Number of Measles Cases, Region of the Americas, 1980 – 2008
Source: PAHO/WHO
Follow-up campaigns
Catch-up campaigns
Routine infant vaccination coverage
Confirmed cases (thousands)

14. Measles Incidence in Regions with Elimination Goal, 2009*
Very low incidence in the Region of the Americas
Mainly imported / import-associated
Consistent with sustained elimination since 2002
Continued virus transmission elsewhere
High reported incidence
Outbreaks
PAHO: 86 cases reported for 2009 (through Mar 10, 2010).
WPRO: Data do not include China (84% of the population).
*As reported to World Health Organization through March 10, 2010.

15. Reported measles cases and measles vaccination coverage, Finland, 1980-2006*
2nd dose started in 1982, but coverage data not reported to WHO. National measles elimination goal est
Measles, mumps & rubella declared eliminated.
*Source of data: World Health Organization.

16. Measles incidence and major outbreaks WHO European Region, 2008-2009
Communicable Diseases Unit, WHO Regional Office for Europe
27 October 2009
Measles incidence and major outbreaks WHO European Region,
Measles outbreaks in
Source: WHO Regional Office for Europe, Copenhagen, Denmark.

17. Reported measles cases, WHO European Region, 2004 – 2009 *
*Source: WHO Regional Office for Europe, Copenhagen, Denmark.

18. Reported Measles Incidence United States, 1992-2008
Measles elimination declared
1 case/million 18

19. Ratio of Indigenously Acquired to Imported Cases, U.S., 2001- 2009*
* 2009 data are provisional

20. Measles Importations into the U.S., by WHO regions, 2005-2009*
*2009 data are provisional

21. Measles, U.S., 2008
In 2008, the U.S. had the largest number of reported cases in over a decade (140 cases)
The epidemiology was characterized by:
High proportion (95%) of cases among unvaccinated U.S. residents
High proportion (96%) of U.S. school-aged children whose parents have claimed exemptions
Many were homeschooled
More spread from imported cases

22. Conclusions Global measles mortality at its lowest level (2008 est.)
90% mortality reduction goal subject to progress in India
Risk of resurgence in Africa?
Region of the Americas was the first and so far is the only region to achieve measles elimination
Measles still widely circulates in all other regions
Two-dose vaccination strategy and high coverage are key for global measles mortality reduction and elimination
In the US, risk of measles remains as long as virus continues to circulate in other countries
Timely 2-dose vaccination according to schedule for ALL children essential to prevent disease and avert outbreaks

23. Acknowledgements Peter Strebel, WHO HQ, Geneva
Edward Hoekstra, UNICEF HQ, New York
Carlos Castillo Solorzano, PAHO, Washington, D.C.
Rebecca Martin, WHO Regional Office for Europe
Laura Zimmerman, CDC Atlanta
Kathleen Gallagher, CDC Atlanta
Susan Redd, CDC Atlanta

24. Contact e-mail: aau5@cdc.gov
Thank You!
Contact
“The findings and conclusions in this presentation have not been formally disseminated by the Centers for Disease Control and prevention (CDC) and should not be construed to represent any CDC determination or policy.”

25. Backup Slides

26. Measles in the U.S., 2009* 69 cases from 18 states and DC
7 (10%) cases hospitalized, no deaths
62 cases in U.S. residents
89 % cases unvaccinated or unknown vaccination status
8 outbreaks reported (3-15 cases)
In 2009 (with only 69 cases)…there were less than half as many cases reported, compared to 140 reported measles cases during previous year of 2008.
10% of cases were hospitalized in 2009, and there were no deaths.
62 Of the case-patients were U.S. residents, 89% of whom have been unvaccinated or have unknown vaccination status.
8 outbreaks ranging from 3-15 cases have been reported.
* Provisional Data

27. Measles Imports 2009
A total of 57 (87%) confirmed cases this year are import-associated
18 imports,
5 foreign visitors (4 unvaccinated/unknown vaccine status)
13 US residents (11 unvaccinated/unknown vaccine status)
15 import-linked cases,
9 virus-only cases,
15 epi-linked to virus-only cases.
The 9 source countries were:
Cape Verde(1) China (2) France (1)
India (5) Italy (1) Philippines (1)
South Africa (1) UK (5) Viet Nam (1).
A total of 57 (87%) confirmed cases this year are import-associated
18 of these were direct imports,
5 foreign visitors (4 unvaccinated/unknown vaccine status)
13 US residents (11 unvaccinated/unknown vaccine status)
15 import-linked cases,
9 virus-only cases,
15 epi-linked to virus-only cases.
The 9 source countries for the 18 imported cases were: Cape Verde (1 US resident), China (2 US residents), France (1 foreign visitor), India (4 US residents, 1 foreign visitor), Italy (1 foreign visitor), the Philippines (1 US resident), South Africa (1 foreign visitor), UK (4 US residents, 1 foreign visitor), and Viet Nam (1 US resident).

28. Measles in the U.S., 2008 25 importations 15 cases unknown source
140 cases from 19 states and DC
18 (13%) cases hospitalized, no deaths
Importation status:
25 importations
12 foreign visitors (all unvaccinated/ unknown vaccine status)
13 US residents (all but 1 unvaccinated/ unknown vaccine status)
100 (71%) additional cases linked to importations or virologic evidence of importation
15 cases unknown source
127 cases in US residents
95% cases unvaccinated or unknown vaccination status
During 2008, 140 measles cases were reported from 19 states and DC.
17 (12%) cases were hospitalized including 6 children under the age of 15 months; no deaths were reported
Twenty five cases were as the result of direct importations from other countries including
12 cases in foreign visitors to the US, all were unvaccinated
And 13 US residents returning from travel, again, all were unvaccinated
An additional 100 measles cases were linked to these importations or had virologic evidence of importation (for example, isolation of a genotype that is known to be circulating abroad)
15 cases had an unknown source of infection
Of the 127 measles cases in US residents, 95% cases unvaccinated or unknown vaccination status

29. U.S. Case-Patients with Unvaccinated/ Unknown Vaccination Status by Age Group, 2001- 2009*
Cases
Percent
The bars along the x-axis of this figure show the breakdown of U.S. case-patients who were unvaccinated or who had unknown vaccination status by age group. You can see that in 2008, the unvaccinated 5-19 year olds represented by the yellow bar, increased compared to previous years (almost all of these claimed personal belief exemptions). You will also notice the higher proportion of cases among U.S. residents in 2008 and 2009 who were unvaccinated or had unknown vaccination status compared with other years, depicted by the white line.
Year
*2009 data through Oct 2

30. Data from the National Immunization Survey
Estimated 1 dose MMR Vaccine Coverage among children aged months, U.S.,
This slide shows MMR vaccine coverage data. Although there is slight variability in MMR vaccine coverage by state, estimated national coverage rates for MMR vaccine in month olds has remained stable over the past few years ranging from 92-93%. National 2-dose MMR coverage rates for year olds is 89.3%.
For your own reference:
During 2008, the lowest MMR coverage was in Montana at 85.9% and the highest in Tennessee at 95.6%.
Data from the National Immunization Survey

31. Large Measles Outbreaks in Pockets of Unvaccinated School-aged Children, 2008
San Diego: 12 cases including 7 school-aged children; none were vaccinated (all were PBE);4 children were exposed in the pediatrician's office. Source was an unvaccinated boy who traveled to Switzerland.
Washington State: 19 cases including 16 school-aged children (11/16 were being home-schooled); none were vaccinated (all were PBE). Possible outbreak source was a Japanese traveler who had attended a youth conference in Washington State.
Illinois: 30 cases including 25 school-aged children (all were homeschooled); none were vaccinated (all were PBE). Likely source was an unvaccinated adolescent traveler returning home from Italy.
During 2008, we had three outbreaks of measles in pockets of unvaccinated school children
Early in the year, 12 cases including 7 school-aged children occurred in San Diego; none of the cases had been previously vaccinated because their parents also had objections to vaccination. 4 children were exposed in a pediatrician's office. The index case was an unvaccinated boy who traveled to Switzerland.
Washington State experienced an outbreak that resulted in 19 cases including 16 school-aged children (11/16 were being home-schooled); none of these children were vaccinated (all were PBE). Possible outbreak source was a Japanese traveler who had attended a youth conference in Washington State.
And in Illinois, 30 cases of measles occured including 25 in school-aged children (all were homeschooled); none were vaccinated (all were PBE). The likely source was an unvaccinated adolescent traveler returning home from Italy.

32. but coverage data not reported
Reported measles cases and measles vaccination coverage, Switzerland, *
2nd dose started in 1996
but coverage data not reported
to WHO until 2006
*Source of data: World Health Organization.

33. Source: Eurosurveillance (21 Feb 2008), available at http://www

34. Source: Eurosurveillance (21 Feb 2008), available at http://www

35. Major Global Measles D5 Virus Transmission Pathways 2006-08
Apr 07
Apr 06
>May 06 D5
Jul 07
Jan 07
Feb 08
>Nov 06 D5
Endemic
D5 endemic in Thailand
D5 outbreak in Japan, started May 2006, no known epi-link. More than 270 cases in 2007, cases continue into 2008 (Jan-March)
D5 cases (one or two cases) Denmark and Sweden April 2006 with epi-links to Thailand
D5- Belarus Jan 2007 single case imported from Thailand
D5 Vancouver April 2007, epi links to Japan. Japanese students assoc with case quarantined in hotel then sent back to Japan.
D5 Switzerland since November 2006 with very close/identical sequences to the D5 virus endemic in Thailand and Japan. No known epi-links associated with the Swiss D5 introduction. The D5 Swiss virus was also linked to spread to Germany, Austria and Denmark. Case count Switzerland 2007; In 2008: 957 cases (March).
D5 in Moscow Jan 07, epi-links to Thailand
D5 New York virus epi-links to Japan (several episodes 2007)
D5 New York July 07 epi links to Switzerland
D5 Switzerland Jan 08. Epi-link and sequence identical to Berlin D5. Berlin D5 identical to the Swiss strain exported to south Germany early 2007.
D5 San Diego Feb 08. Index case just returned from Switzerland. Eleven cases reported, all unimmunised.
D5 Saint-Mandé, France, Feb 08 France (west) identical to Swiss virus, no epi-links, no details of outbreak.
D5 Reims, France, Feb 08, no epi or molecular link to Swiss outbreak.
Acknowledgement:
Data provided by WHO Measles/Rubella Laboratory Network and Measles surveillance programmes
Transmission pathways with Epi links
Suspected transmission pathways 15

36. Measles Outbreaks in the Americas, 2008-2009*
D8/Morocco
D4/Pakistán D8?
D5/?
H1/China D5/Germany
D4? D5/France
N=1
D5/Switzerland D4/Italy
D4/India
N=140
D4/Italy
D4/Italy
D8/NYC D4/Belgium, Israel
N=39
D5/Switzerland
D5/Japan
D4/Pakistan
N=1
D4/India
N=2
D4/England
Outbreaks during:
2008
N=1
2009
N=1
1 dot = 1 case
N=3
*Data up to EW20/2009.
Note: Cases were imported, import-related, or of unknown origin. Source: Country reports to PAHO.
Slide courtesy of Dr. Carlos Castillo Solorzano, PAHO, Washington, D.C. 36

37. Confirmed Measles Cases by Country of Report, The Americas, 2003-2008*
Confirmed cases
N=108
N=85
Source: Country reports to FCH-IM/PAHO.
* Data as of 1 June 2009.

38. Top Ten Causes of Death in Children Aged <5 Years, Worldwide, 2000
Source: World Health Organization, Global Burden of Disease 2000 Project

39. WHO Global Measles and Rubella Laboratory Network: 2001-2007
N= 679 labs
10 Sub-National Labs
Global Specialised Labs
National Laboratories
Regional Reference Labs 80
31 "NLs"
+ 331 "SNLs"
124 Sub-National Labs
164 countries =
Global Specialised Labs
National Laboratories
Regional Reference Labs
172
As of July 2008 39

40. World Health Organization
WHO LabNet Quality- Global Proficiency Test distribution
World Health Organization
11 May, 2018
~430,000 tests run in 2008 for Measles & Rubella IgM detection
Pass rate
China Provincial Labs included 2009
(98.8%)
(98.2%)
(98.5%)
(98%)
(94%)
(90%)
Most of the national level labs are now receiving the same PT panel. China Provincial labs will receive the panels for the first time in The quality of the labs in the LabNet is high as seen in this graph. Almost 99% of the national labs achieved a pass and most achieved 100%.
(94%)
(96%)

41. Reported Measles Incidence by WHO Region, 1980-2008
Elimination
Achieved in (elimination) AMR
2.8 per 100,000* (elimination) EMR
0.6 per 100,000* (elimination) EUR
6.3 per 100,000* (elimination) WPR
* Elimination <0.1 per 100,000
Source: Dr. P. Strebel, WHO, August 2009

42. World Health Organization
11 May, 2018
Measles eradication is biologically feasible (properties of the virus and disease)
Humans are the only host
Life-long immunity after natural infection
Only one serotype
Genetically stable
Challenges:
Highly infectious → high population immunity needed to interrupt transmission
Population growth and density, migration and international travel
HIV epidemic 42

43. World Health Organization
11 May, 2018
Measles eradication is technically feasible (properties of tools for control)
Measles vaccines are safe and effective
Vaccines provide long-term protection against all known genotypes
Accurate diagnostic tests available
Current vaccines have eliminated measles in the Americas
Challenges:
Vaccine needs cold chain and sterile injection
Not effective in early infancy
2 doses needed 43

44. World Health Organization
11 May, 2018
International Task Force on Disease Eradication The Carter Center, June 4, 2009
“Measles eradication is biologically feasible using tools that are currently available, as already demonstrated in the Americas, although implementation challenges remain in each of the remaining five regions." 44

45. Strategic Plan, 2011-2015 EB report on eradication of measles
Eradication is a worthy public health goal that can be achieved
A major obstacle in many countries is inadequate routine immunization systems which must be strengthened as an essential building block for achieving and maintaining regional measles elimination.
2015 targets as a milestone towards eradication
GIVS coverage goals
95% mortality reduction vs 2000
Incidence <5 per million

46. Number of Reported Measles Cases with onset date from Aug 2009 to Feb 2010
0 (76 countries or 39%)
1 – 9 (34 countries or 18%)
10 – 99 (32 countries or 17%)
100 – 999 (20 countries or 10%)
>1000 (7 countries or 4%)
No data reported to WHO HQ
(24 countries or 12%)
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 All rights reserved.
Data source: surveillance DEF file
Data in HQ as of 10 March 2010