Herd immunity and vaccination

Zsofia Meszner MD PhD National Institute of Child Health Szent Lszl Hopital for Infectious Diseases Budapest

Outline
Vaccine preventable infections Vaccination calendar, Hungary 2007
Calendar and optional immunisations

Concept of herd immunity by vaccination Examples:

Morbilli Poliomyelitis anterior acuta Dyphteria Pneumococcus infections

Misconceptions about vaccnination Future trends

27 diseases are now vaccine preventable

Disease
Smallpox Rabies Typhoid Cholera Plague Diphtheria Pertussis Tetanus Tuberculosis Influenza Yellow fever Poliomyelitis Measles Mumps

Year
1798 1885 1896 1896 1897 1923 1926 1927 1927 1945 1953 1955 1963 1967

Disease
Rubella Anthrax Meningitis Pneumococcus pneumonia Adenovirus Hepatitis B H. influenzae type b Japanese encephalitis Hepatitis A Varicella Lyme disease Rotavirus Human papillomavirus

Year
1969 1970 1975 1977 1980 1981 1985 1992 1995 1995 1998 1998 2006

Adapted from CDC MMWR April 2, 1999; 48(12): 243-8

Smallpox

NOTE: before eradication case fatality rate was 10%

Vaccine preventable deaths among children worldwide (WHO 2002)

Poliomyelitis Diphtheria Yellow fever Tetanus Pertussis Hemophilus influenzae type b Measles Pneumococcal disease Rotavirus ADULTS: hepatitis B
CDC: MMWR 2006; 55: 511-5, adapted

<1,000 4,000 15,000 198,000 294,000 386,000 540,000 850,000 600,000 600,000

Clinical Development
Note : Vaccination calendar very ++++ by country (age, schedule, booster doses, etc.) Vacci ati chedules i Europe

Introduction to GCP and Vaccine Tri al Methodology, Limelette 29 March to 1 Apri l 2004

Hungarian Immunisation Schedule

AGE GROUP VACCINE birth BCG 2 months DaPT-IPV-Hib 3 months DaPT-IPV-Hib 4 months DaPT-IPV-Hib 15 months MMR 18 months DaPT-IPV-Hib 6 years DaPT-IPV 6 years DaPT-IPV Vaccination campaigns in schools 11 years dt 11 years MMR booster 14 years Hepatitis B REMARKS In hospitals

In September In October In September, March

Value of vaccines beyond the individual

Individual

Societal

Economic

Value of vaccines for the society

With the exception of clean drinking water, vaccination is the most successful public health intervention Potential for disease eradication Cost-effective, often cost-saving Herd effect leads to broad/global protection

CDC, MMWR 2006;55:511-15

Herd effect (herd immunity)

Immunised individuals provide indirect protection to susceptible (unvaccinated, partially vaccinated) individuals:
fewer people infected lower shedding by vaccinees

T Jacob John & Reuben Samuel. Eur J Epid 2000;16:601-6

Herd effect (herd immunity)

 Most mass vaccination provides herd immunity  Protection occurs even when vaccination coverage is less than 100% of the population  The greater the infectivity (reproductive rate) of a disease, the higher the immunisation rate needed to achieve herd immunity

Basic reproductive rate

R0 = The average number of individuals directly infected by an infectious case during the infectious period, while in a totally susceptible population.

Immunisation and herd immunity

In a homogeneously mixed population, eradication can be achieved if, through immunisation, R0 is brought down to <1. Relationship between Pc (proportion successfully immunised) and R0 (average number of secondary cases from one primary case in wholly susceptible population) is Pc = 1- 1/R0 Thus high R0s will necessitate very high coverage rates

Adapted from Anderson & May, Immunisation and herd immunity Lancet 1990;335:641-645

Morbilli - measels

Measles Epidemics Europe 1999 2007

Country
Holland 1999/2000 Italy 2002

Region
Religious group Genderlacht Campania

Cases
2961* - 137 w/1 dose of
MMR vaccine

Hospitalised
68
(Encephalitis 5)

Died
3
ages 2, 3, 17 yrs

1571?*
101 w/vaccine: - 70 1x MMR - 2 2x MMR - 29 ? MMR

594
(Encephalitis 17)

4
ages 1/2, 4, 10, 29 yrs

Switzerland 20037 Germany 2005/06

Various cantons Various

>800*
- 8.0% 1x MMR - 0.7% 2x MMR

8 (+?)
(Encephalitis 3)

>7000*

* Most of these cases were not vaccinated, but some were * M

Minimum vaccination coverage required to stop infection transmission

Infection Mean age of InterInfectious- Minimum infection epidemic ness index vaccination period coverage (%)

Meas es Pertuss s Mu ps ube a phther a Po o

4-5 4-5 6-7 9-10 11-14 12-15

2 3-4 3 3-5 4-6 3-5

15-17 15-17 10-12 7-8 5-6 5-6

92-95 92-95 90-92 85-87 80-85 80-85

Adapted from Anderson & May, Immunisation and herd immunity Lancet 1990;335:641-645

Sample of Scientific paper #1

Methods: Vaccination history of 100 children with measles has been investigated; Results: All of them were given measles vaccine; Conclusion: The vaccine is absolutely ineffective

Correct calculations

Vaccine failure 5%

Protective efficacy 95%

V.Usonis, 2 CEE, Baden 2005

NONE HAD MEASLES OR RUBELLA !

Note that in 52% of cases, no definite cause could be identified

Parvovirus B19 17% Group A Streptococcus 15%

Adenovirus 4% Group C Streptococcus 3%

Human Herpes 6 6% Enterovirus 5%

Polyomyelitis anterior acuta

Notifications of acute poliomyelitis England & Wales, 1930 - 70

Cases (x 1,000) 80 60
Inactivated vaccine (Salk)

40 20 0
1930 1940 1950 1960

Live attenuated vaccine (Sabin)

1970

Polio outbreaks in Europe 1990 to 2000

Year
1991 1992-3

Country
Bulgaria Netherlands

Cases
43 71

Causal factor
unimmunised minority populations religious refuseniks (97% national vaccine uptake) immunisation programme halted in Chechnya cold chain failure spread to unimmunised minorities [not reported]

1995

Russia

154

1996

Albania

138

1997

Bulgaria

Personal communication: Professor Keith Cartwright

Global polio situation 2003

Kano state will not participate in the polio campaign, Kano government spokesman Sule Yau Sule told the press yesterday. Our team made the discovery of contaminants first, remember. Mr Sule was referring to controversial tests of the polio vaccine made by Kano health officials last year. The tests concluded that the vaccine was not safe as it could spread HIV/AIDS and affect womens fertility.

Global Polio Eradication Initiative Progress 2002 WHO, Geneva 2004

NIGERIA: Muslim suspicion of polio vaccine lingers on

Countries reporting indigenous wild virus polio

(February 2006 to February 2007 no poliomyelitis in the Americas & Europe)

2006: 1119

2006: 672 40 31

http://www.polioeradication.org/content/general/casemap.jpg

: transmission never stopped Global 2006: 1988 cases, including 126 in non-endemic countries

Dyphteria
Francisco Goya 1802-1812

Diphtheria epidemics in Russia and Ukraine

40000

Russia
cases N 10000 0 30000 20000

Ukraine
0 2 82 84 86 88 90 92 94 96 98 4

80

Year

39,703 cases

diphtheria were registered in Russia in 1994

Streptococcus pneumoniae

Herd Effect in Adults

Ma s s va ccina tion re comme nde d for infa nts

40 35

33,6

32 24,6

Cases per 100,000

30 25 20 15 10 5 0

17,6 11,9 9

1998/99

2000

2001

2002

2003

2004

Lexau C et al JAMA 294:2043-51, 2005 and CDC unpublished data, presented by Dr Cynthia Whitney, IDSA 2005

Herd Effect in Adults

Invasive Pneumococcal Disease in Adults, Aged 65 + USA 1998-2004
Mass vaccination recommended for infants
40 35

33,6

32 24,6

Cases per 100,000

30 25 20 15 10 5 0

7 3 % re duction
17,6 11,9 9

1998/99

2000

2001

2002

2003

2004

Le xa u C e t a l JAMA 294:2043-51, 2005 and CDC unpublished data, presented by Dr Cynthia Whitney, IDSA 2005

Effect of PCVs on Pneumococcal Transmission

Herd immunity

Invasive neumococcal Disease in the USA, By Race, Children <5 years old, 1995 2002
250 200 Cases er 100,000 150 Black 100 50 0 1995 1996 1997 1998 1999 2000 2001 2002 White Conjugate vaccine licensed

Vaccination eliminates inequalities

Ref: Flannery B et al. JAMA 2004

Deaths that could be prevented by pneumococcal vaccines

Vaccines are victims of their own success

We have forgotten the seriousness of some diseases

The paradox of concern

Disease

Serious adverse events due to vaccine

Safety of vaccination

RISK of vaccination: Adverse event

RISK of NOT vaccinating: Infection, may be life-threatening

Risk and benefit

"The balance of risk and benefit must weigh most heavily towards the side of benefit. Immunization programs have saved countless of children from death or disability while adding almost nothing to the burden of suffering."
WHO: Weekly Epid Rec 1998; 73:37

Misconceptions about adverse events (AE)

Inaccurate reports in the media Confusion about temporal vs. causal association Lack of media coverage on refutation of alleged adverse events Lack of case definition
trivial AE vs. serious AE vague illness e.g. autism, SUDI

Temporal association vs causal association 2006

4 Israeli patients died after they received influenza vaccination

Are the two events related? Is vaccination the cause of death?

In time, yes. Vaccine targeted at very sick patients: High risk population Confusion: Coincidence vs. cause

Causal relationship denied by the Ministry of Health

Diseases likely to be falsely attributed to vaccines

Disease group
Loose diagnostic criteria Under-ascertained (or no data) Age-associated Autoimmune (antigenic overload) Unknown aetiology Degenerative Other

Example
Learning difficulties, dyslexia, behavioural problems, autism Juvenile IBD SUDI, autism Stills disease, MS Juvenile-onset diabetes, asthma Guillain-Barr syndrome Heart disease Death

Causal relationships demonstrated as questionable: Multiple sclerosis ..... after hepatitis B vaccination
Confavreux C et al. N Engl J Med 2001; 344:319-26: RR (relapse) 0.71 (95% CI 0.4-1.3) DeStefano F et al. Arch Neurol 2003;60:504-9: OR 0.9 (95% CI 0.6-1.5) Hernan MA et al. Neurology 2004;63:838-42: OR 3.1 (95% CI 1.5-6.3) www.med.harvard.edu/AANLIB/cases/case5/temporal/mr-t2

WHO states that there is no causal relationship

Hepatitis B vaccination vs. MS: the French Authorities rationale

Annual cohort of 800,000 high school students (1012 years old)

Risk of Vaccination/yr
? 1 to 2 cases/yr of demyelinating disorders/yr

Benefits of vaccination/30 yrs

329 fulminating hepatitis 12147 cirrhosis and liver cancers

if
that risk exists

prevented
over a 30 year period

Rseau National de Sant Publique - Sept. 98

Dispelling the myth

It is not that there is no evidence, but there is evidence and it does not show an association (with vaccination).
Arlett P et al. Adverse Drug React Toxicol Rev 2001;20:37-45 2001;20:37-

Vaccine development 19002000

With thanks to Professor E Miller

Where are we now?

HIV/AIDS

Future

Malaria Dengue Mening (conj) HPV Rotavirus Pneumo (conj) Typhoid Hib (conj) YF Influenza HepB JE Rubella Measles

TB

Underutilised Vaccines

Cholera

Traditional EPI

Tetanus Polio Pertussis Diphtheria

// 1960 1980 2000

//

Source: WHO 2006

Horizon scanning infectious diseases

Herpes zoster vaccine for senior citizens Meningococcal B Respiratory Syncytial Virus Tuberculosis (replace BCG) Malaria Dengue Hookworm HIV

Future vaccinology paradigm shifts (1)

CURRENT
Goal Diseases Age groups Population Administration Prevention Communicable Mainly children General/ universal Single/multiple

NEW / FUTURE
Also therapy Cancer, other All life stages Also selective populations Combined

Future vaccinology paradigm shifts (2)

CURRENT
Vaccine application Vaccine technology Costs Paid by Safety

NEW / FUTURE

Injected Mucosal patch, edible Traditional Subunit and peptide technology VariableIncreasing Taxation Surveillance Public/private partnership Intensifying

Examples of vaccines against infections which might cause cancer

Hepatitis B vaccine to prevent hepatocellular carcinoma Human papillomavirus vaccine (HPV) for girls (and boys?) to prevent cervical and other cancers

Therapeutic cancer vaccines on the horizon

Prostate
Slovin SF et al. Vaccine 2005;23:3114-22

Melanoma
Wilox R and Markovic SN. Curr Opin Mol Ther 2007;9:7078

Lymphoma
Neelapu SS et al. Blood 2007;[Epub]

Colon, kidney, breast

Vaccines no longer restricted to infectious diseases!

New technology under investigation

New adjuvants vaccines more potent Blowing vaccines through the skin DNA vaccines the gene gun

Fewer jabs
Alternative delivery: nasal sprays, edible vaccines, mucosal patches Combinations of vaccines in syringe Slow release formulations microspheres

Jenner would be proud of us