Up-date on measles elimination in ItalyUp-date on measles elimination in Italy

Roberto GaspariniRoberto Gasparini

Department of Health Sciences Genoa UniversityDepartment of Health Sciences Genoa University

Via Pastore, 1 - 16132 Genoa (Italy)Via Pastore, 1 - 16132 Genoa (Italy)

E-mail address: gasparini@unige.itE-mail address: gasparini@unige.it

City states ofthe Levantc.1500 BC

City states ofthe Levantc.1500 BC

Sumeriac.3000 BC

Sumeriac.3000 BC

Italian city statesc-300 BC

Italian city statesc-300 BC

Egyptiancivilisation

c.1000-500 BC

Egyptiancivilisation

c.1000-500 BC

Indus civilisationc.2500 BC

Indus civilisationc.2500 BC

China: end of theHan dynasty

2200 BC?

China: end of theHan dynasty

2200 BC?

Greek city statesc.1000 BC

Greek city statesc.1000 BC

Japanc.1000 AD ?

Ganges civilisationc.1000 BC

Ganges civilisationc.1000 BC

Probable axis of measles expansionwith the evolution of civilisations

Barriers to measles expansion

Probable axis of measles expansionwith the evolution of civilisations

Barriers to measles expansion

SAHARA DESERT

IRANIANPLATEAU

TIBETANPLATEAU

GOBI DESERT

THE URBAN THE URBAN HEARTHEARTOF MEASLESOF MEASLES

THE URBAN THE URBAN HEARTHEARTOF MEASLESOF MEASLES

Expansion of the Roman Empire

c.200 AD

Expansion of the Roman Empire

c.200 AD

Measles VaccineMeasles Vaccine

After the isolation and propagation of measles virus in tissue After the isolation and propagation of measles virus in tissue culture by Enders and Peebles in 1954, vaccine development, culture by Enders and Peebles in 1954, vaccine development, testing, and licensure quickly followed. After the vaccine testing, and licensure quickly followed. After the vaccine containig the Edmoston A and B strains many further containig the Edmoston A and B strains many further attenuated vaccines have been developed and they are in attenuated vaccines have been developed and they are in active use worldwide (Schwarz, Moraten, Edmoston-Zagreb, active use worldwide (Schwarz, Moraten, Edmoston-Zagreb, ecc).ecc).

Tolerability, safety and effectiveness of Measles vaccines are Tolerability, safety and effectiveness of Measles vaccines are very good.very good.

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Source: WHO/UNICEF joint reporting form, 2002 & WHO SIA Database, WHO/UNICEF Source: WHO/UNICEF joint reporting form, 2002 & WHO SIA Database, WHO/UNICEF estimates 2003estimates 2003data from 192 WHO member statesdata from 192 WHO member states

No data No data (1 countries or 1%)(1 countries or 1%)< 90% < 90% (100 countries or 52%)(100 countries or 52%)

>> 90% 90% (91 countries or 47%)(91 countries or 47%)

No 2No 2ndnd opportunity opportunity (29 countries or 15%)(29 countries or 15%)

Yes 2Yes 2nd nd opportunity opportunity (163 countries or 85%)(163 countries or 85%)

* 2nd Opportunity = country has implemented a two dose routine measles * 2nd Opportunity = country has implemented a two dose routine measles schedule and/or within the last 4 years has conducted a national schedule and/or within the last 4 years has conducted a national immunization campaign achieving immunization campaign achieving >> 90% coverage of children < 5 yrs 90% coverage of children < 5 yrs

Providing 2nd opportunity*, 1998-2002

Achieving 90% measles coverage, 2002

Countries implementing measles mortality Countries implementing measles mortality reduction strategiesreduction strategies

Slide Date: October 03

Measles epidemiology in Italy from Paediatricians and GPs notifications and specific mortality in 1980-1997 period.

0

10000

20000

30000

40000

50000

60000

70000

80000

90000

100000

60 62 64 66 68 70 72 74 76 78 80 82 84 86 88 90 92 94 96 98 0

0

10

20

30

40

50

60

70

80

90

100

N. casiN. decessi

N. of casesN. of cases Vaccination startedVaccination started

N.Cases

N.Deaths

N.of deathsN.of deaths

Percentages of Italian children (15-24 months) who received measles Percentages of Italian children (15-24 months) who received measles vaccine during 1983-2000 period.vaccine during 1983-2000 period.

0102030405060708090

100

198

3

198

4

198

5

198

6

198

7

198

8

198

9

199

0

199

1

199

2

199

3

199

4

199

5

199

6

199

7

199

8

199

9

200

0

anniyears

%

Measles epidemics in Campania Region Measles epidemics in Campania Region (Italy) in 2002(Italy) in 2002

Total cases estimated, in Total cases estimated, in subjects aged 0-14 years, was subjects aged 0-14 years, was 24,000 (2,300/100,000).24,000 (2,300/100,000).

The number of hospitalisations The number of hospitalisations was 368, of which 63 were was 368, of which 63 were cases of pneumonia and 13 cases of pneumonia and 13 encephalytis.encephalytis.

There were 4 deaths.There were 4 deaths.

In the other Italian Regions the In the other Italian Regions the incidence was 77/100,000.incidence was 77/100,000.

MarMar

Incidence of measles in Italian RegionsIncidence of measles in Italian RegionsSPES: Jannuary- August 2002SPES: Jannuary- August 2002

JanJan FebFeb

JuneJuneMayMay

AprApr

JulyJuly AugAug

Molecular Epidemiology: an useful method for Molecular Epidemiology: an useful method for study measles epidemiologystudy measles epidemiology

The measles virus The measles virus has 6 structrural has 6 structrural proteins: P, L, N, F, proteins: P, L, N, F, H and M. The entire H and M. The entire 15,894-nucleotide 15,894-nucleotide long genome have long genome have been sequenced. been sequenced.

The WHO currently The WHO currently recognize 20 recognize 20 genotypes and one genotypes and one proposed genotype proposed genotype of measles virus of measles virus based on based on phylogenetic phylogenetic analysis of the N analysis of the N gene.gene.

A,D2

AA

B

C

CG2

H

MOLECULAR EPIDEMIOLOGY OF MEASLES: A NEW MOLECULAR EPIDEMIOLOGY OF MEASLES: A NEW GENOTYPE ISOLATED IN 2003 DURING AN GENOTYPE ISOLATED IN 2003 DURING AN

OUTBREAK IN LIGURIAOUTBREAK IN LIGURIA •In spring 2003 in Liguria an outbreak of measles was registered In spring 2003 in Liguria an outbreak of measles was registered with a total of 187 cases; the highest incidence was in La Speziawith a total of 187 cases; the highest incidence was in La Spezia

Out of 16 pharingeal swabs collected, 8 were viremic and were Out of 16 pharingeal swabs collected, 8 were viremic and were characterized by nucleic acid sequence analysis of the characterized by nucleic acid sequence analysis of the Nucleoprotein geneNucleoprotein gene (N) and the (N) and the Haemagglutinin geneHaemagglutinin gene (H) (H)

•The philogenetic analysis permitted genotyping of all 8 and The philogenetic analysis permitted genotyping of all 8 and relatediness between the viruses and appropriate reference relatediness between the viruses and appropriate reference sequences was studiedsequences was studied

•Sequences from Liguria formed a distinguished cluster from Sequences from Liguria formed a distinguished cluster from genotypes previously described as D7 genotype, even if with a genotypes previously described as D7 genotype, even if with a difference of 5% with the reference straindifference of 5% with the reference strain

•Molecular epidemiology studies have made a significant Molecular epidemiology studies have made a significant contributions to the identification of source and transmission contributions to the identification of source and transmission pathways of the measles virus and allowed to clarificate pathways of the measles virus and allowed to clarificate epidemiological links during measle outbreaks separating epidemiological links during measle outbreaks separating indigenous strains from newly imported strainsindigenous strains from newly imported strains

Rational of Measles vaccination Rational of Measles vaccination policypolicy

The basic reproductive rate of infectious diseases (RThe basic reproductive rate of infectious diseases (R00) is the ) is the

average number of cases that would be expected to spread average number of cases that would be expected to spread from a single case in a completely susceptible population.from a single case in a completely susceptible population.

Measles is a highly infectious disease, and RMeasles is a highly infectious disease, and R00 has been has been

estimated as 12.5 to 18. So, it has been estimated that to estimated as 12.5 to 18. So, it has been estimated that to achive the goal of Measles elimination it is necessary that the achive the goal of Measles elimination it is necessary that the susceplible subjects are not more than 15% at the age 0-5, susceplible subjects are not more than 15% at the age 0-5, not over 10% between 5 to 9 years children, and no more not over 10% between 5 to 9 years children, and no more than 5% in subjects over 9 years.than 5% in subjects over 9 years.

The goal of Italian plan of measles The goal of Italian plan of measles eliminationelimination

The goal of Italian plan of measles The goal of Italian plan of measles elimination is to maintain, after 2007, elimination is to maintain, after 2007, the measles incidence below 1 case per the measles incidence below 1 case per 100,000 inhabitants.100,000 inhabitants.

Paediatricians, GPs and Paediatricians, GPs and their Scientific Associationstheir Scientific Associations

UniversitiesUniversitiesHospitalsHospitalsScientific Research Scientific Research CentersCenters

How to Plan, to organize and to carry out the How to Plan, to organize and to carry out the Italian Measles elimination policyItalian Measles elimination policy

Experts of PublicExperts of PublicHealth, workingHealth, workingIn the Prevention In the Prevention Department, and Department, and their scientific their scientific AssociationAssociation

Nurses andNurses andSocial workersSocial workers

Local Health AgenciesLocal Health AgenciesCoordinated by Regional Experts Coordinated by Regional Experts and Authoritiesand Authorities

The departments of The departments of Italian Local Health Italian Local Health Agency are the Agency are the Centers for Centers for planning, organizing planning, organizing and carrying out and carrying out measles elimination measles elimination plan. To achieve the plan. To achieve the goal it is neccessary goal it is neccessary that a close that a close collaboration among collaboration among experts of Public experts of Public Health, Health, Paediatricians, Paediatricians, nurses, GPs, and nurses, GPs, and also, Istitutions as also, Istitutions as University, Hospital, University, Hospital, etc.etc.

Measles elimination action planMeasles elimination action plan

• Within 2003: to improve the surveillance system, by virus isolation and Within 2003: to improve the surveillance system, by virus isolation and definition of the clades and genotypes too, for identification of cases as definition of the clades and genotypes too, for identification of cases as imported or indigenous.imported or indigenous.

• Within 2004: increasing coverage of infants until 85%, and improving Within 2004: increasing coverage of infants until 85%, and improving the informatization of vaccination data base.the informatization of vaccination data base.

• Within 2005: implementing the infant measles coverage til 90%.Within 2005: implementing the infant measles coverage til 90%.

• Within 2006: increasing and sustaining high routine coverage (95%), Within 2006: increasing and sustaining high routine coverage (95%), and achiving a 95% coverage rate in children aged 3-15 years, and and achiving a 95% coverage rate in children aged 3-15 years, and maintaining the measles incidence below 1 case per 100,000 inhabitants.maintaining the measles incidence below 1 case per 100,000 inhabitants.

• Within 2007: maintaining the children rate coverage at 95% or over, Within 2007: maintaining the children rate coverage at 95% or over, and increasing the two doses coverage of children aged 5-6 til 90%.and increasing the two doses coverage of children aged 5-6 til 90%.

< 50%

50-75%

>75%

Measles-vaccination coverage of Italian children Measles-vaccination coverage of Italian children

0-24 months0-24 months ICONA 1998 2000

Measles-vaccination coverage of Italian Measles-vaccination coverage of Italian children 0-24 months (August 2004)children 0-24 months (August 2004)

Coverage ratesCoverage rates< 70%< 70%

70-85%70-85%> 85%> 85%

No dataNo data

National mean National mean coverage rate: coverage rate:

83.6%83.6%

Measles-vaccination coverage of Italian Measles-vaccination coverage of Italian children 0-24 months (August 2004)children 0-24 months (August 2004)

Coverage ratesCoverage rates< 70%< 70%

70-85%70-85%> 85%> 85%

No dataNo data

National mean National mean coverage rate: coverage rate:

83.6%83.6%

Causes of refused or delayed MMR Causes of refused or delayed MMR vaccination (font: ICONA, 2003)vaccination (font: ICONA, 2003)

3%

5%

25%

17%6%

18%

5%

3%

18%

non noto

altro

malattia

opinione medico

ha già avuto il morbillo

organizzazione servizio

vaccinerà più tardi

vacc.pericolose/inefficaci/malattia raramalattia poco pericolosa

No data

other

Illness

Unfavorable GP or Pediatricia opinion

Measles in the past

No good organization of vaccination services

Tardy vaccination

Fear of vaccination

Measles is not a severe illness

Give me a gift for a better life:Give me a gift for a better life:

VACCINE ME!!!!VACCINE ME!!!!