1. Measles Epidemiology and Vaccine Policy in the U.S.
Kathleen Gallagher, D.Sc, MPH
NCIRD, CDC
April 2, 2009

2. Outline Background/ History of Measles
Burden of disease globally and in the US
Current epidemiology of measles
Challenges
Strategies for the future
Good morning
Today, I’m going to give you a brief background on measles disease an d vaccine. Then, I’ll spend some time talking about the burden of measles in the US and globally. Next, I’ll spend a bit of time summarizing the current epidemiology of measles, focusing on what happened with measles in the US in We’ll talk about challenges to maintaining measles elimination in the US, and Finally, we’ll talk about measles control strategies for the future.

3. Measles Clinical features: Public health significance: Fever
Maculo-papular rash
Three “C”s:
Cough
Coryza
Conjunctivitis
Public health significance:
Highly communicable
May cause complications
CFR: 0.1 – 15%
Measles is a highly infectious, acute viral disease caused by the measles virus.
Personse with measles usually develop a distinctive maculopapular rash, high fever, The three C’s, cough, coryza, conjunctivitis and Koplik Spots, oral lesions pathognomonic for measles. Complications such as otitis media, bronchopneumonia, and diarrhea are common in children. Measles can cause especially severe disease in people who are malnourished or who have underlying immunocompromising medical conditions such as HIV infection or cancer. The CFR varies from about 0.1 to 15%
Photo courtesy of Professor Samuel Katz,
Duke University Medical Center.

4. 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: 750,000 deaths (estimate)
Global mortality burden mostly in Africa and Asia
In the era before measles vaccine was licensed, measles was a nearly universal childhood and it was estimated that 135 million cases and more than 6 million deaths occurred worldwide ever year. A safe and effective vaccine for measles was licensed in 1963v and measles vaccine was incorporated into the WHO’s Expanded Programme on Immunizations about a decade later. Although this had an impact on the global disease burden, the death toll from measles remained high with millions of death still occurring every year. The majority of this these measles deaths occurred in Africa and Asia.

5. 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
A global strategy to drastically reduce global measles-associated mortality was launched by the Measles Initiative early in this decade with a goal of achieving a 50% reduction by This goal was met ahead of time and under-budget. As a result, a revised goal of achieving a 90% reduction in measles deaths by 2010 was promoted. Key strategies to accomplish this goal include
Improving medical management of measles cases
Improving 1st does coverage for measles vaccine
Offering 2nd opportunities for measles immuinization, and
Strengthening disease surveillance
*Lancet, 2007 Jan 20;369(9557): ¶

6. Routine 1st Dose Measles Vaccination Coverage, by WHO Region, 2000 & 2007
82%
As a result of these efforts, substantial improvements in measles vaccine coverage between 2000 and 2007 have occurred in most WHO regions. Globall 1 dose Measles vaccine coverage in 2007 was 82%.
Source: MMWR 2008; 57(48):

7. Impact of Global Measles Mortality Reduction Efforts, 2000 - 2007
WHO Region
Estimated deaths
2000
2007
% reduction in deaths
Africa
395,000
45,000
89%
Americas
<1,000 -
Eastern Mediterranean
96,000
10,000
90%
European
SE Asia
235,000
136,000
42%
W. Pacific
25,000
7,000
73%
TOTAL
750,000
197,000
74%
Source: MMWR 2008; 57(48):

8. Annual Measles Disease Burden United States, 1950s
3-4 million cases
~ 500,000 reported cases
Severe complications
4,000 encephalitis cases
150,000 respiratory complications (pneumonia)
48,000 hospitalizations
450 deaths
In the US in the pre-vaccine era, approximately 500,000 cases of measles were reported in U.S. citizens annually. However, it was generally believed that due to its highly infectious nature, measles most likely infected the entire birth cohort meaning that in any given year, 3-4 million people would have been infected with the disease During this time period, complications due to measles were frequent and costly with approximately 150,000 pts developing respiratory complications each year. In addition, approximately 4,000 cases of encephalitis occurred in measles patients ever year, many of these resulting in long term sequelae. Approximately 48,000 hospitalizations and 450 deaths were reportedly due to measles each year in the pre-vaccine era.

9. Reported Measles Cases 1st Dose Recommendation
United States,
1963
Vaccine Licensed
1st Dose Recommendation
Measles Cases
Measles vaccine was first licensed in the US in and as this slide shows resulted in a dramatic reduction in reported measles cases by the end of that decade. In 1966, just 3 years after the licensure of the vaccine , the first efforts targeting measles elimination in the US were declared and steady progress was being made towards this objective during the seventies and eighties.
Resurgence
Year

10. Measles, United States, 1985 - 2007
1989
2nd Dose
Recommended
Measles resurgence
55,622 reported cases
123 reported deaths
Reported Measles Cases
However, A major resurgence of measles resulting in over 55,000 cases and 123 deaths occurred between 1989 and 1991 and was associated with low measles vaccine coverage among pre-school aged children and primary vaccine failure in some adults who previously received a dose of vaccine. As a result, a 2 dose measles vaccine recommendation was implemented during this time period. Currently , most measles vaccine in the US is administered as combined measles, mumps, and rubella or MMR vaccine.
Year

11. Reported Measles Incidence United States, 1992-2007
Measles elimination declared
1 case/million
After the initiation of the policy that recommended routine use of 2 doses of MMR vaccine in children, further declines in measles incidence occurred through the 1990’s. You can see that the incidence of measles has been well below 1 case per 1 million for every year since In 2000, measles was declared eliminated from the U.S., a remarkable public health success. Elimination is defined as the absence of endemic disease transmission.

12. Measles Epidemiology, Post Elimination
63 cases reported each year ( )
Cases are all related to imported cases including from developed countries – Europe, Japan
Outbreaks predominantly in unprotected populations
In the US,, in the measles post-elimination era from 2000 through 2007, an average of 63 cases have been reported annually.
Virtually all of the cases have been related to importations from other countries; many of them developed countries in Asia and Europe,
Outbreaks occurred predominantly in unprotected populations such as an outbreak in Indiana during 2005 that resulted in 34 cases in an unvaccinated religious community.
In 2006, a measles outbreak in Boston, resulted in 18 cases in young adults. Most of the cases were either foreign born and many had previously received one dose of vaccine.

13. Measles, US, 2008
Highest number of reported cases year to date since 1996
No increase in imported cases
Increase in spread within the U.S.
7 “outbreaks”
But the measles story in the US has changed a bit in Last year, we have had the highest number of measles cases reported in 12 years.
And although importations were still occurring, this increase did not appear to be related to increased importations within the US but rather an increase in spread within the US.
During 2008, 7 outbreaks of measles occurred in the US, predominantly in unvaccinated children. These outbreaks were highlighted in 3 MMWR articles that were published last year.
This upsurge in measles cases has received much media attention in the US.

14. Measles, US, 2008 140 cases from 19 states and DC
17 (12%) cases hospitalized, no deaths
Importation status:
24 importations
13 foreign visitors (all unvaccinated)
11 US residents (all unvaccinated)
102 (73%) additional cases linked to importations or virologic evidence of importation
14 cases unknown source
127 cases in US residents
91% 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-four cases were as the result of direct importations from other countries including
13 cases in foreign visitors to the US, all were unvaccinated
And 11 US residents returning from travel, again, all were unvaccinated
An additional 102 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)
14 cases had an unknown source of infection
Of the 127 measles cases in US residents, 91% cases unvaccinated or unknown vaccination status
Postscript: Since the end of July, we have had 7 additional cases of measles reported throughout the US. These have been scattered among various geographic areas including NY, MN, WA State, IL including one additional importation

15. Measles Cases Reported to CDC, 2008 (N= 140)
Grant County, WA
Outbreak N=19
Vernon County, WI
N=1
Chicago, IL
N=1
Chaves Co, NM N=1,
Missaukee County, MI Outbreak, N=4
Milwaukee County, WI Outbreak, N=6
Nassau County, NY N=1
Portland, OR N=1,
Pittsburgh, PA N=1
Suffolk Co, NY N=1
San Francisco, CA N=2
Boston, MA N=2
Santa Clara, CA N=1
New York City, NY
N=27
Bergen, NJ N=1
Los Angeles, CA N=1
San Diego, CA
Outbreak N=12
(CA =11, HI =1)
This map shows the geographic location of these 140 cases. You can see that the cases are dispersed throughout the US. Yellow dots depict sporadic cases. The seven outbreaks that happened during 2008 are highlighted in pink. During 2008, there were sizeable measles outbreaks in in Washington State, San Diego, AZ, IL, and NYC.
Fairfax, VA N=1
D.C. N=1
Cass Co, MO N=1
Baton Rouge , LA N=1,
Honolulu, HI
N=4
Fulton Co, GA N=1
Du Page Co, I L Outbreak N=31
Hillsborough Co, FL N=1
Pima County, AZ Outbreak N=14
Scott County, AR
N=2
Boone Co, IL N=1

16. Reported Measles Cases, U.S. 1997-2008*, by Importation Status
This slide shows the number of reported measles cases each year that have been due to direct importation over the past decade. During 2008, 24( 17% of the total number of) cases were importations , 11 in US residents who traveled abroad and 13 in foreign visitors. This is the lowest percentage of directly imported measles cases since Over 70 % of these importations were associated with countries in the WHO EURO region
*Provisional data through December 31, 2008

17. Measles Importations, U.S. 2008
140 cases
24 importations D5 D4 D4 D4 D5
This map shows the routes of transmission for US imported measles cases during Its quite noticeable how many cases were imported from Europe where many countries are experiencing sizeable measles outbreaks. We had multiple importations in 2008 from Switzerland, Belgium, Italy and Israel. Genotypes D4, D5, and H1 have been isolated from cases this year.
Measles Importations, U.S. 2008

18. U.S. Residents with Measles, January-December 2008, by Age
During 2008, measles cases occurred primarily in children and adolescents including 17 cases in children under the age of 12 months for whom vaccine is not yet recommended. These children count on the herd immunity that others provide to protect them from disease. 80% of measles cases in 2008 were in persons under the age of 20.
N = 127
80% cases < 20 years

19. Reason For Not Being Vaccinated— Unvaccinated U. S
Reason For Not Being Vaccinated— Unvaccinated U.S. Residents With Measles, 2008*, N= 116
Missed opportunity, delayed, other reasons
<12 months of age
17(15%)
1(1%) Born before 1957
31(27%)
This figure describes the reason for not being vaccinated among the 116 unvaccinated US residents with measles reported during 2008.
15% were too young to be routinely vaccinated because they were under 12 months of age.
1 person was born before 1957, and therefore considered to be immune because of birth year.
27% were unvaccinated due to missed opportunity, delayed vaccination, or unknown reasons. This group includes mostly children aged months who have not yet been vaccinated or older toddlers who parents have delayed vaccination but don’t necessarily have any religious or personal objections to vaccination.
Finally, the vast majority, 57% were unvaccinated due to their own or their parents personal or religious beliefs.
67(57%)
Personal or religious beliefs
* Provisional data reported to NCIRD through 12/31/08

20. US Measles Cases Aged 5-19 Years Claiming Personal Belief Exemptions (PBE), 2001- 2008*
Percent
You can see from this graph that a major difference between the epidemiology of measles in 2008 compared to other post-elimination years is that a higher proportion of cases aged 5-19 years claimed personal or religious belief exemptions (93% in 2008 compared to 0-87% from ).
Of note, during 2005, there was a large outbreak of measles in Indiana that was focused in a community with religious and personal objections to vaccination, the largest measles so far this decade…
* Provisional data reported to through 12/31/08, US residents only

21. 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.

22. Estimated MMR Vaccine Coverage among children aged 19-35 months , NIS, US, 2003-2007
So how does this recent upsurge in measles cases correspond with what we know about MMR vaccine coverage in the US?
This slide shows data from the National Immunization Survey collected over the past few years. Estimated national coverage rates for MMR vaccine in month olds has remained stable ranging from a high on 93% in to 91.5 in For the past two years, coverage of MMR vaccine has been 92.3.
There is variability in MMR vaccine coverage by state. During 2007, the lowest MMR coverage was in Idaho (85.1%), the highest at 97.1% in Maryland. MMR vaccine coverage rates are expected to be higher in children who are 4-6 year of age because school entry requirements for vaccines come into play.
Data from the Adolescents NIS survey …last published for the year 2006, showed an overall MMR coverage rate for teens aged of 87%.

23. Vaccine Coverage
Overall one-dose MMR coverage in month olds in US in 2007 was 92.3%
CA : 94.6%, WA :85.1%, IL: 93.1%
91.5% in SD County during 2006
Kindergarten survey ( )
2 dose MMR coverage: CA:94.6%, WA: 90.9%, IL:93.5%
% of children with religious or philosophical exemptions: CA: 1.6%; WA:5.9%, IL: 2.7%
So how do these findings correspond with what we know about MMR vaccine coverage in the US. Data collected from the national immunization survey on one-dose MMR coverage in month olds over the past 10 years has been more or less stable between 90 and 93% with a coverage of 92.3% being reported in MMR-1 coverage for CA, WA and IL are 94.6, 85.1 and 93.1% respectively. Although not available in 2007, estimates for MMR-1 coverage in San Diego county was 91.5% in 2006, slightly lower than the state average that year.
In addition, data submitted by state immunization programs from results of their Kindergarten surveys for the school year show high two dose coverage for MMR in these three states reporting outbreaks with a range of almost 91% in WA State to almost 95% in California. Statewide, between 1.6% and 5.9% of children attending kindergarten report having religious of philosophical beliefs against exemptions. It is important to note that states use a variety of different methods in their kindergarten surveys. For example, both WA and CA include home-schooled children in their surveys but IL does not; CA does the survey in a sample of schools but IL an WA each use a census.
Based on these data, we might not feel too concerned about the number of cases of measles that we have seen this year.

24. Personal Belief Exemptions in Kindergarteners, San Diego County, 2008 *
As part of our investigation into the measles outbreak in San Diego, the local EIS officer in conjunction with the County Health Department have looked more closely at personal exemptions for each school within the county. This map shows the different school districts, district specific exemptions rates ( the white to dark blue shading) and school-specific exemption rates show in the yellow circles. You can see that some school have exemption rates in excess of 20% and that furthermore, this level of exemption might be masked if we were to look at only district specific rates.
In my mind, these data, should al least give us pause about whether or not we should be worried about pockets of personal belief exemptions in the US
* Courtesy of D. Sugerman et al.

25. Summary –Measles 2008
In 2008, the US saw the largest number of cases reported in over a decade
The epidemiology of measles was characterized by:
High proportion of cases among U.S. residents who are unvaccinated
High proportion of cases in school-aged children whose parents have claimed exemptions
Many of these children were homeschooled
More spread from imported cases
In summary, during 2008 the U.S. has seen more measles cases than any other year in the post-elimination era. The epidemiology of measles has been characterized by a higher proportion of cases among U.S. residents who are unvaccinated or who have unknown vaccination status, a higher proportion of cases in school-aged children, many of them home-schooled, whose parents have religius or philosophical objections to vaccination, and more spread from imported cases in these unprotected populations.
* Need to mention homeschooling and the fact that imports are mostly from EURO this year.

26. Measles 2009 9 cases (8 US residents) reported from 5 states
All cases this year import-associated:
7 imports, 2 import-linked cases,
Source countries for the 7 imported cases were: Cape Verde, India , Italy and UK (4 US residents)
Of the 8 cases among U.S. residents
6 (75%) were unvaccinated or had unknown vaccination status
3 (60%) were <12 months of age
1 case (11%) because of personal or parental beliefs.
2 unknown

27. Global Measles Global achievements in measles control and elimination
In 2008, measles endemic in many countries, outbreaks in Europe and UK declared re-establishment of endemic disease transmission
WHO Euro >8,000 cases
Switzerland >2,000 cases
UK > 1,400 cases
In 2006, ~30 million U.S. residents traveled abroad and 51 million international visitors entered the U.S.
Ongoing risk of importations
As I’ve shown earlier, a remarkable amount of progress has been made worldwide in control and elimination efforts for measles.

28. Measles Outbreaks in the WHO European Region, September 2007 – August 2008
Low Income Country
Lower Middle Income Country
Upper Middle Income Country
High Income Country
MEASLES OUTBREAKS
Gibraltar, UK
Source: Dr. R. Martin, WHO Regional Office for Europe, Copenhagen, Denmark.

29. Challenges in Maintaining Measles Elimination in the US
Ongoing risk of importations
Lack of familiarity among travelers, the public and health care providers
High level of response effort by local, state and national public health and laboratory staff
Maintaining high 2-dose vaccination coverage rates

30. Strategies for Maintaining Measles Elimination
Adequate Surveillance
Detect imported cases to prevent indigenous spread
Detect small chains of transmission
Timely and complete reporting and notification of cases
Rapid Outbreak Response
Case finding and investigation
Contact tracing
Assess need for community vaccination
Maintain high 2 dose MMR coverage

31. Future Directions Continue to monitor MMR vaccination coverage rates
Monitor the impact of vaccine exemption, and understand reasons for vaccine exemptions
Increase awareness for measles in
Public
Health Care Providers
Travelers (especially to highly developed countries)

32. Acknowledgements Charley LeBaron Al Barskey Daoling Bi Susan Redd
Amy Parker
Preeta Kutty
Huong McLean
Amra Uzicanin
Bill Bellini
Paul Rota
Jenny Rota
Luis Lowe
Jane Seward
Greg Armstrong
State and local health departments

33. Thanks

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

35. Source: Eurosurveillance (21 Feb 2008),
vailable at

36. 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