1. Up-date on measles elimination in Italy Roberto Gasparini Department of Health Sciences Genoa University Via Pastore, 1 - 16132 Genoa (Italy) E-mail address: gasparini@unige.it

2. City states of the Levant c.1500 BC City states of the Levant c.1500 BC Sumeria c.3000 BC Sumeria c.3000 BC Italian city states c-300 BC Italian city states c-300 BC Egyptian civilisation c.1000-500 BC Egyptian civilisation c.1000-500 BC Indus civilisation c.2500 BC Indus civilisation c.2500 BC China: end of the Han dynasty 2200 BC? China: end of the Han dynasty 2200 BC? Greek city states c.1000 BC Greek city states c.1000 BC Japan c.1000 AD ? Ganges civilisation c.1000 BC Ganges civilisation c.1000 BC Probable axis of measles expansion with the evolution of civilisations Barriers to measles expansion Probable axis of measles expansion with the evolution of civilisations Barriers to measles expansion SAHARA DESERT IRANIAN PLATEAU TIBETAN PLATEAU GOBI DESERT THE URBAN HEART OF MEASLES THE URBAN HEART OF MEASLES Expansion of the Roman Empire c.200 AD Expansion of the Roman Empire c.200 AD

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

8. Source: WHO/UNICEF joint reporting form, 2002 & WHO SIA Database, WHO/UNICEF estimates 2003 data from 192 WHO member states No data (1 countries or 1%) < 90% (100 countries or 52%) > 90% (91 countries or 47%) No 2 nd opportunity (29 countries or 15%) Yes 2 nd opportunity (163 countries or 85%) * 2nd Opportunity = country has implemented a two dose routine measles schedule and/or within the last 4 years has conducted a national immunization campaign achieving > 90% coverage of children 90% coverage of children < 5 yrs Providing 2 nd opportunity*, 1998-2002 Achieving 90% measles coverage, 2002 Countries implementing measles mortality reduction strategies Slide Date: October 03

9. Measles epidemiology in Italy from Paediatricians and GPs notifications and specific mortality in 1980-1997 period. N. of cases Vaccination started N.Cases N.Deaths N.of deaths

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

11. Measles epidemics in Campania Region (Italy) in 2002 Total cases estimated, in subjects aged 0-14 years, was 24,000 (2,300/100,000). The number of hospitalisations was 368, of which 63 were cases of pneumonia and 13 encephalytis. There were 4 deaths. In the other Italian Regions the incidence was 77/100,000.

12. Mar Incidence of measles in Italian Regions SPES: Jannuary- August 2002 JanFeb JuneMay Apr JulyAug

13. Molecular Epidemiology: an useful method for study measles epidemiology The measles virus has 6 structrural proteins: P, L, N, F, H and M. The entire 15,894-nucleotide long genome have been sequenced. The measles virus has 6 structrural proteins: P, L, N, F, H and M. The entire 15,894-nucleotide long genome have been sequenced. The WHO currently recognize 20 genotypes and one proposed genotype of measles virus based on phylogenetic analysis of the N gene. The WHO currently recognize 20 genotypes and one proposed genotype of measles virus based on phylogenetic analysis of the N gene. A,D2 A A B C CG2 H

14. MOLECULAR EPIDEMIOLOGY OF MEASLES: A NEW GENOTYPE ISOLATED IN 2003 DURING AN OUTBREAK IN LIGURIA In spring 2003 in Liguria an outbreak of measles was registered with a total of 187 cases; the highest incidence was in La SpeziaIn spring 2003 in Liguria an outbreak of measles was registered with a total of 187 cases; the highest incidence was in La Spezia Out of 16 pharingeal swabs collected, 8 were viremic and were characterized by nucleic acid sequence analysis of the Nucleoprotein gene (N) and the Haemagglutinin gene (H) The philogenetic analysis permitted genotyping of all 8 and relatediness between the viruses and appropriate reference sequences was studiedThe philogenetic analysis permitted genotyping of all 8 and relatediness between the viruses and appropriate reference sequences was studied Sequences from Liguria formed a distinguished cluster from genotypes previously described as D7 genotype, even if with a difference of 5% with the reference strainSequences from Liguria formed a distinguished cluster from genotypes previously described as D7 genotype, even if with a difference of 5% with the reference strain Molecular epidemiology studies have made a significant contributions to the identification of source and transmission pathways of the measles virus and allowed to clarificate epidemiological links during measle outbreaks separating indigenous strains from newly imported strainsMolecular epidemiology studies have made a significant contributions to the identification of source and transmission pathways of the measles virus and allowed to clarificate epidemiological links during measle outbreaks separating indigenous strains from newly imported strains

15. Rational of Measles vaccination policy The basic reproductive rate of infectious diseases (R 0 ) is the average number of cases that would be expected to spread from a single case in a completely susceptible population. The basic reproductive rate of infectious diseases (R 0 ) is the average number of cases that would be expected to spread from a single case in a completely susceptible population. Measles is a highly infectious disease, and R 0 has been estimated as 12.5 to 18. So, it has been estimated that to achive the goal of Measles elimination it is necessary that the susceplible subjects are not more than 15% at the age 0-5, not over 10% between 5 to 9 years children, and no more than 5% in subjects over 9 years. Measles is a highly infectious disease, and R 0 has been estimated as 12.5 to 18. So, it has been estimated that to achive the goal of Measles elimination it is necessary that the susceplible subjects are not more than 15% at the age 0-5, not over 10% between 5 to 9 years children, and no more than 5% in subjects over 9 years.

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

17. Paediatricians, GPs and their Scientific Associations UniversitiesHospitals Scientific Research Centers How to Plan, to organize and to carry out the Italian Measles elimination policy Experts of Public Health, working In the Prevention Department, and their scientific Association Nurses and Social workers Local Health Agencies Coordinated by Regional Experts and Authorities The departments of Italian Local Health Agency are the Centers for planning, organizing and carrying out measles elimination plan. To achieve the goal it is neccessary that a close collaboration among experts of Public Health, Paediatricians, nurses, GPs, and also, Istitutions as University, Hospital, etc.

18. Measles elimination action plan Within 2003: to improve the surveillance system, by virus isolation and definition of the clades and genotypes too, for identification of cases as imported or indigenous.Within 2003: to improve the surveillance system, by virus isolation and definition of the clades and genotypes too, for identification of cases as imported or indigenous. Within 2004: increasing coverage of infants until 85%, and improving the informatization of vaccination data base.Within 2004: increasing coverage of infants until 85%, and improving 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%), and achiving a 95% coverage rate in children aged 3-15 years, and maintaining the measles incidence below 1 case per 100,000 inhabitants.Within 2006: increasing and sustaining high routine coverage (95%), and achiving a 95% coverage rate in children aged 3-15 years, and maintaining the measles incidence below 1 case per 100,000 inhabitants. Within 2007: maintaining the children rate coverage at 95% or over, and increasing the two doses coverage of children aged 5-6 til 90%.Within 2007: maintaining the children rate coverage at 95% or over, and increasing the two doses coverage of children aged 5-6 til 90%.

19. < 50% 50-75% >75% Measles-vaccination coverage of Italian children 0-24 months ICONA 1998 2000

20. Measles-vaccination coverage of Italian children 0-24 months (August 2004) Coverage rates < 70% 70-85% > 85% No data National mean coverage rate: 83.6%

21. Measles-vaccination coverage of Italian children 0-24 months (August 2004) Coverage rates < 70% 70-85% > 85% No data National mean coverage rate: 83.6%

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

23. Give me a gift for a better life: VACCINE ME!!!!