Epidemiological aspects of Vaccine Preventable Diseases (VPD)

1. Epidemiological aspects of Vaccine Preventable Diseases (VPD) Biagio Pedalino

2. What’s so special about VPD?

3. Vaccines: what are they? A vaccine is a biological preparation (microorganism, toxoid, subunit) Stimulates the body's immune system to create antibodies against this microorganism A vaccine aims to safely protect a healthy individual/population from a particular infection Vaccines need to be assessed before and after licensing

4. Objectives of the presentation To define key aims and effects of different vaccination programmes To identify key principles in vaccination programme evaluation Disease surveillance Vaccine uptake (coverage) Vaccine effectiveness Vaccine safety

5. Aims of vaccination programmes To protect those at highest risk (selective vaccination strategy) or To eradicate, eliminate or control disease (mass vaccination strategy)

6. Selective vaccination strategy Vaccine given specifically to those at increased risk of disease High risk groups e.g. pneumococcal, meningococcal Occupational risk e.g. hepatitis B, influenza Travellers e.g. yellow fever, rabies, hepatitis A Outbreak control e.g. hepatitis A, measles

7. Selective vaccination strategy Vaccine targeted at a specific group (although risk of disease affects another) Girls and young women (~13-26 yrs) e.g. HPV, rubella Pregnant women e.g. tetanus (neo-natal tetanus)

8. Mass vaccination Eradication Infection (pathogen) has been removed worldwide e.g. smallpox Elimination Disease has disappeared from one area but may remain elsewhere, e.g. polio, measles Control Disease no longer constitutes a significant public health problem in certain countries, e.g. neo-natal tetanus

9. Progress Toward Polio Eradication Decrease of >99% from >350 000 cases in 1988 to <2000 cases in 2008 35,251 cases

10. How do mass vaccination programmes impact the disease? Reduce size of susceptible population Reduce number of cases Reduce risk of infection in population Reduce contact of susceptibles to cases Lengthening of epidemic cycle (“honeymoon phase”) Increase mean age of infection

11. All susceptible

12. Basic reproductive number:R0=4

13. Mass vaccination

14. Mass vaccination

15. Effective reproductive number:R < 1

16. Impact of mass vaccination programmeAnnual measles notifications & vaccine coveragePoland 1960-2000 Source: National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland

17. Objectives of the lecture To understand key aims and effects of different vaccination programmes To understand key principles in vaccination programme evaluation, specifically Disease surveillance Vaccine uptake (coverage) Vaccine effectiveness Vaccine safety

18. Considerations behind the epidemiology of vaccine-preventable diseases Surveillance reflects programme vaccination history and disease dynamics (e.g. change age of vaccination; change number of doses) Immunization is population-based role of herd immunity Vaccine efficacy needs monitoring

19. Surveillance of VPD Pre-implementation estimate burden decide vaccination strategy Post implementation monitor impact and effectiveness Nearing elimination identify pockets of susceptibles certification process

20. Impact of mass vaccination programmeAnnual measles notifications & vaccine coveragePoland 1960-2000 Source: National Institute of Public Health – National Institute of Hygiene, Warsaw, Poland

21. Surveillance of VPD Disease incidence (before and after introduction of vaccine) Vaccine uptake (coverage) Vaccine effectiveness Serological surveillance Adverse events Knowledge and attitudes

22. Key data to collect for surveillance of vaccine preventable diseases Person Age Place Residence Time Date of disease onset Date of specimen collection Vaccination status Vaccine failure or failure to vaccinate?

23. Additional data for diseases of special interest or being eliminated Person Age, gender, profession, etc. Place Residence, possible sites of exposure, hospital, etc. Time Date of rash onset, location during possible exposure period, location during infectious phase, etc. Vaccination status Number of doses Date of doses

24. Disease incidence Main sources of data statutory notification laboratory reporting death registrations Other sources hospital episodes sentinel GP reporting paediatric surveillance

25. Surveillance of vaccine coverage Number of vaccines distributed Number of vaccines administered sampling population assessment, e.g. cluster total population assessment (administrative) Number of doses of vaccine given/used Total (target-)population

26. Use of administrative coverage data Usually total population Monitor trends over time Look for pockets of poor coverage Compare with disease epidemiology Estimate vaccine effectiveness

27. Efficacy, effectiveness, herd immunity and impact Efficacy is the direct protection to a vaccinated individual as estimated from clinical trial Effectiveness is an estimate of the direct protection in a field study post licensure Herd immunity is an indirect effect of vaccination due to reduced disease transmission Impact is the population level effect of a vaccination programme. This will depend on many factors such as vaccine coverage, herd immunity and effectiveness

28. Vaccine evaluation observational studies Vaccine effectiveness: protective effect under ordinary conditions of a public health programme prone to bias, more complex interpretation randomised, blinded, controlled clinical trials Vaccine efficacy: protective effect idealised conditions Randomised Controlled Trials (RCT), simple interpretation Post-licensing Pre-licensing

29. Efficacy versus effectiveness Vaccine efficacy Preventable fraction among exposed (Vaccinated) Study conditions Independent of vaccine coverage Vaccine effectiveness Preventable fraction in the population Field conditions

30. Factors influencing field vaccine efficacy (effectiveness) Host age at vaccination (e.g., measles, influenza) immune status (e.g., measles) number and timing of doses (e.g., Hepatitis B) years since vaccination (e.g., pertussis) Vaccine production storage (e.g., temperature, light) transportation route of administration Agent strains included in the vaccine formulation

31. Methods to assess VE Pre-licensure: randomised control trial (RCT) Post-licensure:observational/field investigation cohort study / case-control study screening method household contact study

32. Calculating the vaccine efficacy in the field: Reference method Proportion of cases potentially avoided among vaccinated Preventable fraction among exposed to a vaccine Formula VE = (ARNV - ARV) / ARNV (Cohort study) VE = 1-OR (Case control study) Require a confidence interval

33. ARV = 2/10 = 0,2 ARU = 9/10 = 0,9 0,9 – 0,2 0,9 VE= = 78% Vaccinated Unvaccinated

34. Calculating the vaccine efficacy in the field: Rapid screening method PCV: Proportion of cases vaccinated PPV: Proportion of the population vaccinated VE: Vaccine efficacy Orenstein WA et al. Field evaluation of vaccine efficacy. Bull World Health Organ 1985; 63:1055-68

35. Impact of vaccine coverage on vaccination status of cases assuming VE < 100% Vaccine Coverage 100 % 0 Cases may be vaccinated or unvaccinated All cases vaccinated; All are primary or secondary vaccine failures All cases unvaccinated No vaccine has 100% efficacy

36. Potential pitfalls.... case definition vaccine history case ascertainment comparability of vaccinated/unvaccinated groups

37. Methodological issues:case definition Lower specificity: case definition based only on clinical criteria may result in false-positive diagnoses ARV > ARU VE (%) = (ARU-ARV) X 100 ARU artificial reduction in VE

38. Methodological issues:case definition Changes in mumps vaccine effectiveness Kim Farley et al 1985 AJE

39. Methodological issues:case definition Changes in mumps vaccine effectiveness Kim Farley et al 1985 AJE

40. Methodological issues:vaccine history ascertainment avoid misclassification of vaccination status equal effort to confirm vaccination status among cases and non-cases vaccination histories should be documented using GP, clinic, vaccination cards or computer records persons with missing vaccination records should be excluded

41. Vaccine effectiveness:post licensure monitoring of VE Maintenance of VE Problems in vaccine delivery cold chain failure, schedule violation, n° of doses, vaccine strain substitution Epidemiological factors pathogen changes Methodological bias selection bias, confounding, chance effects Low protective efficacy bad batch, different target population, alternative patterns of use, vaccine strain used

42. Herd immunity Definition Resistance of a group to a disease to which a large proportion of the members are immune Decreases the probability of contacts between infected patients and susceptible individuals * Depends on: Infectiousness of the agent Hepatitis A lower than measles Population density Target herd immunity for measles control 95% in general May be lower in lower population density areas * Adapted from Fox, et al. Am J Epidemiol. 1971; 94:179-89

43. What is different about surveillance of vaccine preventable diseases? It’s not just about the disease Decision making is a complex issue Objectives change at different stages It includes vaccine effectiveness Adverse events following immunization (AEFI) - Vaccine safety issues Case definitions have to change as the epidemiology changes Surveillance methods have to change as the epidemiology changes Follow-up of cases in more detail (remember vaccination status) Vaccination programs have indirect effects Surveillance includes Coverage Surveillance includes Attitudes N. Crowcroft Agency for Health Protection and Promotion, Ontario, Canada

44. Reference Orenstein W. Assessing vaccine efficacy in the field. Epidemiological Reviews 1988 Questions? Acknowledgments: EPIET Vaccination module HPA Immunisation Training (Richard Pebody, Nick Andrews, John Edmunds, Natasha Crowcroft, Mary Ramsay) Revised by:Richard Pebody 2007, Pawel Stefanoff 2008, Marion Muehlen 2009, 2010, Biagio Pedalino 2011, 2012