Epidemiology and Global Control of Measles and

RubellaPeter M. Strebel, MBChB

National Immunization ProgramCenters for Disease Control and Prevention

Global Vaccine Research Forum Montreux, Switzerland

8-10 June 2004

Aim and Outline

Aim: introduction to session

Outline:

– Global disease burden

– Epidemiologic characteristics

– Vaccine properties

– Control strategies

Estimated Global Disease Burden: Vaccine Preventable Diseases Among Children

Disease Global BurdenMeasles (2002) 610,000 deathsHib 450,000 deathsPertussis 285,000 deathsNeonatal tetanus 200,000 deathsCRS (1996) 110,000 casesYellow fever 30,000 deathsDiphtheria 5,450 deathsParalytic Polio (2003) 784 cases

Source: World Health Report 2004; data for 2002; Cutts & Vynnycky Int J Epidemiol 1999

Disease Control Goals

Measles RubellaGlobal Eradication No NoGlobal Control Yes* NoRegional Elimination

Americas 2000 2010E. Mediterranean 2010Europe 2010W. Pacific Date to be set

*WHA 2003: 50% reduction in deaths by 2005 vs. 1999

Estimated measles deaths by WHO region, 2001

050,000

100,000150,000200,000250,000300,000350,000400,000450,000500,000

AFRO SEARO EMRO WPRO EURO PAHO

>98% occur ineligible

countries

WHO/UNICEF priority countriesWHO/UNICEF priority countries

for measles mortality reduction, 2001for measles mortality reduction, 2001

45 countries representing 94 % of all measles deaths45 countries representing 94 % of all measles deaths

Countries/territories using a rubella containing vaccine in their NIP, 2004*

Source: WHO Department of Vaccines and Biologicals, December 2003

Yes (124 countries/territories, 57%, 99% children one year old in the Americas)

No ( 91 countries/territories, 43%)

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.

Haiti

* May 2004 in the Americas

Epidemiologic Characteristics

Feature Measles RubellaOccurrence worldwide worldwideReservoir human humanTransmission respiratory respiratory

person to person person to personCommunicability high* moderate**Seasonality late winter late winterInter-epidemic interval† 2-3 years 6-9 years

*airborne droplet nuclei**subclinical cases transmit and CRS cases may transmit for ~year† prevaccine era

Contagiousness of Common Childhood Communicable Diseases

Source: Anderson & May, Nature 1985, 318:323-9.

Average Age at Infection (years)

Disease IndustrializedLess

Industrialized

Measles

Mumps Chickenpox RubellaPolio

5-6 (USA, 1955-8)

6-7 (England, 1975-7)6-8 (USA, 1912-28)9-10 (USA, 1966-8)12-17 (USA, 1955)

1-2 (Senegal, 1964)1-2 (Bangkok, 1967)

2-3 (Gambia, 1976)

Herd Immunity Threshold

• Younger average age of infection, more contagious the disease

• More contagious, higher herd immunity level needed

• HI threshold = 1-1/Ro

Where Ro (basic reproductive no.) =average no. secondary cases in a fully susceptible population

Comparison of Herd Immunity Thresholds

Basic Reproductive number Ro 12 – 18 Ro 6-10

Herd Immunity threshold 92-95% 83-90%

Measles Rubella

Measles and Rubella Vaccines

Feature Measles RubellaComposition Live virus* Live virus*Effectiveness 85% (9m) 95-100% (9m)

95% (12m)Waning antibodies Yes YesDuration of protection Lifelong LifelongSchedule 2 doses 1 dose

(or 2 opportunities)

*attenuated live virus

Adverse Events Associated with Measles and Rubella Vaccines

Event Measles/RubellaFever 5-15%Rash 5%Febrile seizure* 1/3000Thrombocytopenia 1/30,000Joint symptoms** 1%

25% (adult female)Anaphylaxis ~1/1,000,000Encephalitis ~1/1,000,000

*No association with residual febrile disorder**No association with chronic arthropathy

Control Strategies

• Country examples– Finland– Albania– PAHO Region

Purpose of Vaccination

Goal Measles RubellaControl protect individual protect individual

prevent deaths prevent CRSyoung children pregnant women

Elimination protect community protect community stop transmission stop transmissionpopulation immunity population immunity

Finnish Experience

• 1982 2 dose MMR strategy– At 14-18m and 6y

• Very strong public health system• Very high coverage (~95%) with each dose• 1986 last CRS case • 1993 measles eliminated • 1996 last rubella case

Peltola et al., NEJM, 1994;331:1397-1402

Albanian Experience

• Population 3.4 mil, isolated until 1990s• No rubella vaccination prior to 2000• Nov 2000 MR mass campaign

– 1-14 years– Coverage >95%

• Jan 2001 MMR at 12m and 5 years• Sep 2001 MR women 16-35y (routine services)

– Ongoing post-partum vaccination

Reported Incidence of Rubella and CRS in Albania

• 1960 rubella notifiable• Pre-vaccine era

– Outbreaks every 5-7 years– School children, majority <15 years

• 2001 10 rubella cases• 2002-3 zero confirmed measles or rubella cases• 2002-3 zero CRS cases

Measles and rubella eliminated ??

PAHO ExperienceVaccination Strategies for Elimination

Measles

• Catch-up campaign (1-14y)

• Keep-up - achieving and maintaining high routine vaccination coverage using MMR vaccine

• Follow-up campaigns at least every 4 years, targeting 1-4 year olds, using MR vaccine

Rubella

• Introduction of MMR into the routine childhood program

• Adults males and females mass campaigns using MR vaccine

(The upper age range for men and women targeted for vaccination will depend on the year of the introduction the vaccine, follow-up campaigns, epidemiology and fertility rates in their country.)

Vaccination Coverage & Reported Number of Measles Cases, The Americas, 1990 – 2003*

0

50000

100000

150000

200000

250000

300000

90 91 92 93 94 95 96 97 98 99 2000 2001 2002 20030

20

40

60

80

100

Cases Coverage

Source: PAHO/WHO: Data sent by countries; 50 cases confirmed as of 10 April 2004

Catch-up campaigns

Follow-up campaigns

Routine vaccination coverage (%

)Con

firm

ed c

ases

(tho

usan

ds)

PAHO

105

Confirmed Measles in the Americas by Rash Onset and Genotypes, January 2001 - May 2004*

0

50

100

150

200

250

1 5 9 13 17 21 25 29 33 37 41 45 49 1 5 9 13 17 21 25 29 33 37 41 45 49 1 5 9 13 17 21 25 29 33 37 41 45 49 1 5 9 13 17

Genotypes

D9D6

H1 (Import, Asia)Others, unknown

*Source: Country reportsAs of EPI week 19

EPI Weeks

Cas

es

2001 2002 2003

End

of tr

ansm

issi

on o

f gen

otyp

e D

6

End

of tr

ansm

issi

on o

f gen

otyp

e D

92004

Importations

Annual number of reported rubella cases and number of countries reporting rubella, the Americas, 1982-2004*

020406080

100120140

82 84 86 88 90 92 94 96 98 '00 '02 '04

Year

Rep

orte

d ca

ses

Thou

sand

s

0

10

20

30

40 Countries reporting

Cases Countries reportingSource: PAHO-MoH*As of EPI Week 19

Measleseradication goal is

set

Accelerated Rubella Control

0

50,000

100,000

150,000

200,000

250,000

300,000

82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 '00 '01 '02 '030

20,000

40,000

60,000

80,000

100,000

120,000

140,000

* Three year moving averages

Reported rubella cases

Rep

orte

d m

easl

es c

ases

Trends in reported measles and rubella cases

Region of the Americas, 1982-2003*

Measles Rubella

2 12

35020

0 040

102030405060708090

80 82 84 86 88 90 92 94 96 98 00 2Year

Cas

es (

in th

ousa

nds)

02004006008001,0001,2001,4001,6001,8002,000

Dea

ths

Cases Deaths

Catch-upCampaigns

Reported measles cases & deaths by year, 7 Southern African Countries, 1980-2003

Partnership for Reduction of Measles Mortality in Africa 2001–2003

• Partners: ARC, UNF, UNICEF, WHO & CDC

•Measles campaigns in 29 countries

•112 million children immunized

•Est.170,000 deaths averted annually*

*WHO Weekly Epi Rec, 2004

Nationwide

Sub-national

Percent reduction in estimated measles deaths by WHO Percent reduction in estimated measles deaths by WHO region between 1999 and 2002region between 1999 and 2002

-40-35-30-25-20-15-10

-50

AFR EMR SEAR Others Global

Region

% r

educ

tion

Summary

• Significant preventable disease burden

• Due to failure to vaccinate with measles and rubella vaccines

• Extensive experience with safety and effectiveness

• Elimination possible with existing vaccines and strategies– High coverage 2 dose and 2nd opportunity strategies

• As measles is controlled rubella “emerges” as a public health problem

• Progress toward 2005 mortality reduction goal

Acknowledgements

Drs Jon Andrus and Carlos Castillo, PAHO

Drs Brad Hersh and Susan Robertson, WHO/HQ

Drs Susan Reef and Mark Papania, NIP, CDC