# Presentation: 124165

## Jane Seward, MBBS, MPH
Acting Deputy Director, Division Viral Diseases 
Centers for Disease Control and Prevention

- Acting Deputy Director, Division Viral Diseases
- Centers for Disease Control and Prevention

**FDA BPAC Meeting **
**Bethesda, August 16****th****, 2007**

**Measles Epidemiology****United States, 2006**

**Notes:**
Good afternoon.  I am delighted to be here today to share with you 10 years of experience from the United States with implementing a national varicella vaccination program. 

## Measles

- Highly contagious viral illness
- Near universal childhood infection in the pre-vaccine era
- Morbidity and mortality 1950s, United States
- 450 deaths annually
- 48,000 hospitalizations
- 4,000 cases encephalitis

## Measles Prevention

- Live, attenuated measles vaccine licensed 1963
- Almost all administered as MMR vaccine
- Efficacy
- One dose ≥ 12 months: 95%
- Two doses at least 4 weeks apart ≥ 12 months: 99%
- Schedule: 2 doses
- Children 4-6 years (school students)
- College students
- Health care workers
- International travelers

## Strategies to Control and Eliminate Measles, US 

- Maximize population immunity to measles
- Deliver the first dose on time
- Increase second dose coverage in school children
- Vaccinate high risk adults
- Assure adequate surveillance
- Respond rapidly to  outbreaks
- Work to improve global control

**Notes:**
Our measles elimination strategy is fairly simple.  We strive to achieve high population immunity through delivering the first dose of MMR on time to children 12 – 15 months of age, providing at second dose to school children at school entry and vaccinating high risk adults, such as health care workers.  We work to enhance surveillance and assure it is adequate.  We respond rapidly to outbreaks and we work with sister countries to improve global control of measles.

## Reported Measles Cases
by Year, United States, 1950-2006

- by Year, United States, 1950-2006

- Vaccine
-  licensed

- School immunization laws
-  started in all states

- Second dose strategy
-  and school laws

- Improved first dose
- preschool coverage

## Reported Measles IncidenceUnited States, 1992-2006*

- 1 case/million

- *provisional 2006 data

- Measles elimination declared

**Notes:**
Since 1992 reported incidence has been below 1 case per 100,000 and for the years 1997-1999 incidence is below 1 case per million population. There were less than 500 cases reported in 1993, 1995 and 1997-1999.  For 1997-1999, there are few outbreaks and the largest outbreaks are small.  The largest outbreak in this period consisted of 33 cases, all other outbreaks had less than 20 cases.
Incidence < 1/100,000 since 1992, <1/million for 1997 -1999

## Measles Cases by Age GroupUnited States, 1976-2006

## Measles Cases by Age GroupUnited States, 1976-2006

## Age Specific Incidence of Measles, 1996-2006

## Largest Measles OutbreaksUnited States, 1999-2006

| 
1
2 | LOCATION
Indiana
Boston, MA | Cases
34
18 | Year
2005
2006 | Age Group
Adult
Adult | Origin
Imported
Imported |
| --- | --- | --- | --- | --- | --- |
| 3 | Bedford Co, VA | 15 | 1999 | Preschool /Adult | Imported |
| 4
5 | Multi-state
Multnomah Co, OR | 14
13 | 2001
1999 | Preschool /Adult
Preschool /Adult | Imported
Unknown |
| 6
7 | Lee County, AL
South King Co, WA | 13
12 | 2002
2001 | Infant/ Daycare
Preschool/Adult | Imported
Imported |
| 8
9
10 | Delaware County, PA
Oswego, NY
Multi-state | 11
10
9 | 2003
2004
2000 | School
Infant/Adoptees
School | Imported
Imported
Unknown |
| 11
 | Brooklyn, NY
 | 9
 | 2000
 | Preschool
 | Imported

 |
|  |  |  |  |  |  |

**Notes:**
These are the 11 largest outbreaks in 1999-2006.    A surveillance system consistently detecting outbreaks in this size range is unlikely to be missing larger outbreaks. 

## Age Distribution of Measles CasesUS, 2001-2006

- * Provisional

## Vaccination Status Measles CasesUS, 2001-2006

- * From NNDSS

## Internationally Imported Measles Cases, 1985 – 2006

## Measles Genotypes and Measles Cases USA: 1980-2005

**97 **

**Measles Cases**

**80**

**81**

**82**

**83**

**84**

**85**

**86**

**87**

**88**

**89**

**90**

**91**

**92**

**93**

**94     **

**0**

**5,000**

**10,000**

**15,000**

**20,000**

**25,000**

**30,000**

**95**

**96**

**Interruption in **

**transmission **

**99**

**98**

**00**

**Viral Genotypes**

**G1**

**(2 ****strains in 1983)**

**D3**

**(30 ****isolations)**

**A, C2, B2, B3, D2, D4, D3, D5, **
**D6, D7, D8, G2, H1, H2**

**(>100 ****isolations)**

**0****1**

**0****2**

**0****3**

## Imported Measles Cases1996-2005*

- Total Cases Imported  - 348
- Japan - 50 cases
- China - 36 cases
- Germany - 26 cases
- India - 23 cases
- Philippines - 19 cases
- Italy - 17 cases
- Pakistan - 15 cases
- Greece, United Kingdom – 11 cases each
- 54 other countries  – 140 cases

- *2005 provisional data through Oct 29

## Measles in the U.S.—2006*

- 55 cases reported by 16 states
- States reporting  largest  number of cases:              MA (18), NY (10), CA (6)  &  FL (4)
-  52 cases (95%) were imported-associated cases:
- 31 imports
- 20 epi-linked to imported cases
- 1 virus only case
- 3 cases were  unknown source cases

***CDC data, unpublished**

**Notes:**
Slide not cleared as of July 17, 2006
Not published as of July 18, 2006. Data from Susan Redd, Measles Branch

## Source Countries for 2006 Imported Measles Cases (N=31)

- India     		6
- Ukraine 		6
- China     		5
- U.K.       		3
- Pakistan  		2
- Australia  		2
- Italy         		1
- Hong Kong 		1
- Thailand   		1
- Kenya  		1
- Ethiopia  		1
- Uganda  		1
- Yemen  		1

## 2006 Measles Outbreaks

- 4 outbreaks:
- MA (18 cases) resulting from single import from India --  Office Building(s)
- FL (3 cases) among cruise ship employees, source Ukraine
- NYS (3 cases) among Immigrants living in a Yemen community
- CA (1 case) WA (1 case) MO (1 case) - 3 mothers exposed in China during adoptions

## Cases in US in 2006 with genotype associated with case(s) or outbreaks

**Indiana**

**New York City**

**17 cases: **
**D8 [India]**

**Boston**

**1 case: D6 [Ukraine]**

**1 case:**
**D8 [India]**

**1 case:**
**D6 [Ukraine]**

**1 case : H1 [Hong Kong]**

**Oregon**

**1 case: B3 **
**[inter’l travel, UK]**

**     ****2 cases: B3**
**[travel: Disneyworld]**

**3 cases: B3**
**[Yemen]**

**1 case: D4**
**[Pakistan]**

**1 case:**
**D8 [inter’l**
**travel**
**Australia]**

**1 case:**
**B3 [UK]**

**1 case: H1**
**[China]**

## Cases in US in 2005 with genotype associated with case(s) or outbreaks

**33**

**34 case outbreak: **
**D4 [Romania]**

**Indiana**

**1**

**Illinois**

**1 case: D9 Indonesia] **
**         ****&**
**   ****1 case: D8 [India]**

**1**

**1 case: D6**
**[Armenia]**

**Arizona**

**1**** ****case:D8 [India]**

**2 cases: D4**
**[inter’l travel, **
**Germany]**

**3**

**1 case: D4 [Yemen]**

**1 case: D4**
**[inter’l meeting, France]**

**1 case: B3**
**[Kenya]**

**New York**
**   ****City**

**& 1 case: D4**
**[Romania]**

**2**

**3**

**3 cases: B3**
**[inter’l travel, Mexico]**

**Texas**

**Washington**

**Wisconsin**

**2**

**1**

**Michigan**

**New Jersey**

**New York**

## Evidence for Elimination
 of Endemic Measles in the U.S.

-  of Endemic Measles in the U.S.

- Extremely low incidence
- Majority of cases are internationally imported or import associated
- Surveillance system is adequate
- Population immunity is very high
- No endemic strain of measles virus

## Adequate Surveillance to Detect Endemic Measles

- Consistent detection of imported measles cases
- Detection of isolated cases and small outbreaks
- High level of investigative effort for measles
- Molecular typing consistent with elimination of indigenous genotype of measles virus

**Notes:**
The current surveillance system is adequate to detect endemic rubella if it were occurring: because of consistent detection of imported rubella caes, detection of isolated cases and small outbreaks and high level of investigative effort for rubella and CRS.

## High Population Immunity

- First dose coverage > 90% since 1996 for 19-35 month-old children
- First dose coverage > 97% for school-age children
- Second dose required for 82% of school children as of 2001
- Seroprevalence 1999-2004 shows 96% immunity  (EIA) ages 6-49 years

## Prevalence of Measles AntibodiesU.S Population, 1988-1994

- Hutchins SS et al, JID 2004

- 93% ≥ 6 years
- Born < 1957  99%
- Born >= 1957 87%
- Born 1967-76  81%

## Duration of Vaccine Induced Immunity? 

- US has used measles vaccine since 1963
- Some vaccine recipients received measles vaccine 40 years ago
- Younger cohorts are not being exposed to wild measles virus
- Important to monitor population immunity including whether immunity remains above the protective level

## Persistence of Measles Antibodies After 2 Doses

- of Measles Vaccine in a Postelimination Environment

*LeBaron CW, Beeler J, Sullivan BJ et al.  **Arch Pediatr Adolesc Med. 2007;161:294-301*

## Projected Measles Antibody Levels following MMR2 Vaccination at Kindergarten Age

- A, Titers in the kindergarten group
- B, Percentage potentially susceptible in the kindergarten group.

## Persistence of Vaccine-Induced Measles Antibody 

- Small long term follow up study of persons from vaccine trial in 1971
- Participants 26-33 years after last measles vaccine dose
- No known exposures to measles
- All 56 participants had PRN antibody ≥ 1:8
- 9% had PRN titer ≤ 120
-    (not considered protective)
- Cellular immunity?

- Dine MS, Hutchins SS et al JID 2004

## Conclusions

- Measles no longer endemically transmitted in U.S.
- Almost 100% cases are import associated
- Importations continue to challenge population immunity
- Extremely limited spread from importations due to high population immunity
- No indication of immunity waning to “susceptibility” from epidemiological data
- Continue long term monitoring of vaccine-induced immunity

## Thank You