Vaccination: A Cornerstone of

Public Health

TH Tulchinsky MD MPH
Braun School of Public Health
Dec 2008

1
Licensed Vaccines in Routine Use in the United States, 1980 and 2008

2
Smith, J. C. et. al. Ann Intern Med 2009;150:45-49
3
 Vaccine Preventable Deaths and the Global
Immunization Vision and Strategy, 2006-2015

• Priorities in PH interventions
• VPD deaths can be averted if existing vaccines used at full
potential
• 2002 deaths from diseases for which vaccines are WHO
recommended
• <1,000 children <5 died from polio;
• 4,000 children died from diphtheria;
• 15,000 children died from yellow fever;
• 198,000 children died from tetanus;
• 294,000 children died from pertussis;
• 386,000 children died from (Hib) Hemophilus influenzae type b);
• 540,000 children died from measles
4
5
6
 Vaccination and Prevention

The Greeks had two gods of health. Aesculapius and

Hygiea, therapy and prevention, respectively.
Medicine in the twentieth century retains those two
concepts, and vaccination is a powerful means of
prevention. What follows is information on the
vaccines that together with sanitation, make modern
society possible, and that if wisely used will continue
to bestow on mankind the gift of prevention, which
according to proverb is worth far more than cure.

Source: Plotkin SA, Mortimer EA. Vaccines. Philadelphia: WB

Saunders, 1988 [Introduction].
7
 Millennium Development Goals
2015

1. Cut poverty by half ($1/day)

2. Universal Primary Education
3. Gender equality in education
4. Cut Infant Mortality and <5 MR by 2/3rds
5. Reduce maternal MR 75%
6. Reduce HIV/AIDS & malaria
7. Sustainable environment
8. Implement full sustainable development
strategies 8
 Vaccines

A suspension of live or killed

microorganisms or antigenic portion of
those agents presented to a potential host to
induce immunity to prevent the specific
disease cause by that organism.

9
 Preparation of Vaccines I

• Live attenuated organisms passed repeatedly in tissue

culture or chick embryos so they lose their capacity
to cause disease, but retain ability to induce antibody
response, such as polio (Sabin), measles, rubella,
mumps, yellow fever, BCG, typhoid and plague.
• Inactivated or killed organisms which have been
killed by heat or chemicals yet retain ability to
induce antibody response; are generally safe but less
efficacious than live vaccines and require multiple
doses; e.g. polio (Salk), influenza, rabies and
Japanese encephalitis.
10
 Preparation of Vaccines II

• Cellular fractions: usually polysaccharide fraction

of the cell wall of a disease causing organism, such
as pneumococcal pneumonia or meningococcal
meningitis
• Recombinant vaccines: produced by use of specific
DNA sequences spliced by molecular engineering
techniques to vaccinia virus grown in cell culture
to produces an effective influenza and Hepatitis B
vaccines
• Antitoxins and toxoids

11
Introduction of first generation of vaccines for
use in humans
Originals After World War II

• 1798 Smallpox • 1955 Injectable Polio

• 1885 Rabies Vaccine (IPV)
• 1897 Plague • 1962 Oral Polio Vaccine
• 1923 Diphtheria (OPV)
• 1926 Pertussis • 1964 Measles
• 1927 Tuberculosis (BCG) • 1967 Mumps
• 1927 Tetanus • 1970 Rubella
• 1935 Yellow Fever • 1981 Hepatitis B

Plotkin SA, Mortimer EA 12

 Vaccines used by the Expanded
Programme on Immunization (EPI)

From 1974 onwards Added later

• BCG • Yellow Fever (in
• Polio endemic countries)
• DTP • Hepatitis B
• Measles* • MMR used in
industrialized
countries and now in
many developing
countries

13
 Vaccine Preventable Diseases (VPDs)
• World immunization coverage up from 10% in
1970s to 80% in 1990s, then to 77% in 2004
• Smallpox eradication achieved 1982
• Polio eradication 2005-2010
• Measles still kills >0.4 million per year, need for a
two dose policy (MMR)
• Many new vaccines available and coming
• Costs effectiveness and priorities
• Reinforce success e.g. Sanipeds in former USSR
• Coverage is good; Adapt and expand 14
 Vaccination Issues
• Political support • Strategies
• Professional recognition • Select target groups
• Financing • Coverage
• Expanding vaccine • Herd immunity
capability • Cold chain and logistics
• Organization, delivery, • Continuous up-dating
follow up • International and “gold
• Reporting “up and down standards”
and sideways” (UDS) • Infectious and chronic
• Program content diseases
15
 New Vaccines and Combinations
• Hepatitis B (and A) catch up
• Haemophilus influenza b (Hib) - universal
• MMR, Measles, mumps, rubella x 2 - universal
• DPT x 4 - update policies, catch up and adult boosters -
• Varicella and catch up, also for elderly (H Zoster)
• Influenza – all ages
• Pneumococcal pneumonia – all ages
• Rotavirus
• Human Papilloma Virus (HPV) and cancer cervix
• Future vaccines – streptococcus, cytomegalovirus (CMV),
helicobacter, HIV, malaria, avian flu
• Cocktails – maximum combination of routine vaccines
• New methods of production of vaccines 16
 Vaccines by Period of Development
Eighteenth century: Smallpox (1798)
Nineteenth century: Rabies, Hog cholera, Diphtheria antitoxin,
Cholera, Plague, Typhoid (1896)
Early twentieth century: BCG tuberculosis, Pertussis (1926)
Diphtheria (1923), (1927) Influenza (1936) Tetanus toxoid (1927),
Yellow fever (1935) Rickettsia (1936), Influenza A (1936)
Post-World War II: Yellow fever (1953) Influenza (1945) Diphtheria
toxoid (1949), Tetanus toxoid (1949), Pneumococcus (1976-83),
Typhoid (1952), Polio Salk (1955), Meningococcus (1962), Polio,
Sabin (1963), Measles (1963), Mumps (1967), Tick-borne
encephalitis Rubella (1970), Anthrax (1970), MMR (1971)
1980–1999: Adenovirus, Rabies, (1980, human), Hemophilus influenz
b, Hepatitis B (1987) Typhoid (1992), salmonella, Japanese
encephalitis, Hepatitis B (1981), Varicella (1995), Pertussis
acellular (1993), Lyme disease (1998) Hepatitis A (1995), Rotavirus
(1998)
2000–2010: Pneumococcal, meningococcal disease, influenza,
parainfluenza, human papillomavirus (HPV)
Future: H. pylori,, streptocococcus, HIV, hepatitis C, adenoviruses 17
“Drug company chief urges faster introduction
of new vaccines in poor nations”
• Head of GlaxoSmithKline urges faster introduction of new life
saving vaccines in poor countries; avoid customary lengthy
delays.
• Many new vaccines are becoming a reality against rotavirus,
pneumococcal disease, and cervical cancer
• “These vaccines are there, so it’s important to introduce them
today in developing countries and not 20 years later.”
• With the exception of the rotavirus vaccine, introduced in
Latin America and Europe at the same time, so far vaccines
had been introduced in developing countries 10-20 years after
developed countries had received them.
• What we expect now is that these vaccines be introduced in
the poorest countries. “The money is there, the science is
there.”

18
BMJ 2006;333:11 (1 July).
 Target Groups
• Newborns - Hep B, DPT, Polio, BCG
• Infants – Hep B, DPT, Polio (IPV, OPV), Hib, Hep A,
MMR, pneumococcal pneumonia, influenza, rotavirus
• Pre-schoolers –catch up
• School age children - dT, MMR
• Teen agers – catch up Hep B, MMR
• Adult women - Rubella
• Chronically ill – Influenza, pneumococcal pneumonia
• Travelers – yellow fever, polio, dT
• Adults - dT
• Elderly - Influenza, pneumococcal pneumonia, dT
• Risk groups for bioterrorism – smallpox, anthrax 19
 Tetanus incidence per 100000
0.3

0.25

0.2

Denmark
Israel
0.15 Russian Federation
United Kingdom
Uzbekistan

0.1

0.05

0 20
1970 1980 1990 2000 2010
 Pertussis incidence per 100000
400

300

Denmark Denmark
Israel
200 Russian Federation
United Kingdom
Uzbekistan

UK
100

0 21
1970 1980 1990 2000 2010
 Congenital rubella incidence per 100000
0.15

Denmark
Israel
0.1

Denmark
Israel
Russian Federation
United Kingdom
Uzbekistan

0.05

UK

0 22
1980 1985 1990 1995 2000 2005 2010
 Rubella incidence per 100000
1000

900 Israel

800

700

UK
600
Denmark
Israel
500 Russian Federation
United Kingdom
Uzbekistan
400

300

200

100

0 23
1970 1980 1990 2000 2010
 Diphtheria incidence per 100000
30

25

Russia
20

Israel
Russian Federation
15 Turkey
United Kingdom
Uzbekistan

10

0 24
1970 1980 1990 2000 2010
 Tuberculosis incidence per 100000
100

Russia
90

80
Uzbekistan
70

60
Israel
Russian Federation
50 Turkey
United Kingdom
Uzbekistan
40

Turkey
30

20

UK
10

0
Israel 25
1970 1980 1990 2000 2010
 Viral hepatitis B incidence per 100000
50

40

30
Finland
Israel
Russian Federation
United Kingdom

20
Russia

10

0 26
1985 1990 1995 2000 2005 2010
 Hospital discharges, infectious and
parasitic diseases per 100000
1500

1000

Finland
Israel
Russian Federation
United Kingdom

500

0 27
1985 1990 1995 2000 2005 2010
 Clinically diagnosed AIDS incidence per 100000
4

Finland
Israel
2 Russian Federation
United Kingdom

0 28
1970 1980 1990 2000 2010
 Haemophilius influenza type b invasive
disease incidence per 100000
2.5

1.5
Finland
Israel
Russian Federation
United Kingdom

0.5

0 29
1990 1995 2000 2005 2010
CDC Recommended Immunization Schedule,
0 to 6 years, US, 2009

30
 WHO 1998 Targets of Infectious Disease
Eradication / Control

• Eradication of Chaga's disease by 2010

• Eradication of neonatal tetanus by 2010
• Eradication of leprosy by 2010
• Eradication of measles by 2020
• Eradication of trachoma by 2020
• Reverse trend of increasing tuberculosis
• Reverse trend of increasing HIV/AIDS

31
 Criteria for Assessing Eradicability of Diseases:
International Task Force for Disease Eradication
• Scientific Feasibility
– Epidemiologic vulnerability; lack of non-human reservoir, ease of
spread, no natural immunity, relapse potential;
– Effective practical intervention available; vaccine or other
primary preventive or curative treatment, or vectoricide that is
safe inexpensive, long lasting and easily used in the field;
– Demonstrated feasibility of elimination in specific locations, such
as an island or other geographic unit.
• Political Will/Popular Support
– Perceived burden of the disease; morbidity, mortality, disability
and costs of care in developed and developing countries;
– Expected cost of eradication;
– Synergy of implementation with other programs;
– Reasons for eradication versus control.
CDC. International Task Force for Disease Eradication. MMWR.1992;41:40-2 32
 Eradication or Control of VPDs
Since eradication of smallpox, discussion of possibility of eradicating
other diseases
Potential candidate diseases emerged; some abandoned because of
practical difficulties with current technology
Diseases under discussion for eradication - measles, TB, and some
tropical diseases e.g. malaria and dracunculiasis
Eradication - no further cases of a disease occur anywhere in nature;
continued control measures may be unnecessary e.g. smallpox,
polio (?)
Reducing epidemic and endemic VPDs in selected areas or target
groups, and achieve local elimination
Local elimination is where domestic circulation of a virus is
interrupted with cases occurring from importation only
Strong, sustained immunization program, adaptation to changing
epidemiologic patterns e.g. age groups, importation
33
 Risk Groups Recommended for Annual
Influenza Vaccination, 2005
• All persons aged >65 years (or 55);
• Nursing homes and other chronic-care facility residents of any age
who have chronic medical conditions;
• Adults and children with chronic disorders of the pulmonary or
cardiovascular systems, including asthma;
• Adults and children in medical follow-up or hospitalization during
preceding year for chronic metabolic diseases (e.g. diabetes mellitus),
renal dysfunction, hemoglobinopathies, immunosuppression (by
medications or by HIV); or with conditions (e.g. cognitive
dysfunction, spinal cord injuries, seizures or other neuromuscular
disorders) which compromise respiratory function;
• Children, adolescents (aged 6 months--18 years) on long-term aspirin
therapy and, therefore at risk for Reye syndrome after influenza;
• Women who will be pregnant during the influenza season; and
• Children aged 6--23 months.

Source: CDC. Prevention and Control of Influenza. Recommendations of the Advisory Committee
34
on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2005;54(RR);1-40
 Infant, Child and Adolescent
Immunization Schedule US CDC, MMWR. 2006

35
 Recommended Adult Immunization Schedule, United States, 2002-2003 Recommended Immunizations for Adults with Medical Conditions, United States, 2002-2003

For all persons in this Catch-up on For persons with For all persons in Catch-up on For persons with
this group childhood vaccinations medical / exposure indications Contraindicated
age group childhood vaccinations medical / exposure indications

Age Vaccine
19-49 years 50-64 years 65 years and older Tetanus- Influenza Pneumo- Hepatitis Hepatitis Measles Varicella*
Vaccine Diphtheria coccal A Mumps
B*
(Td)* (poly- Rubella
Medical saccharide) (MMR)*
Tetanus, Diphtheria 1 dose booster every 10 years1
(Td)* Conditions

Pregnancy A
1 dose annually for persons
with medical or occupational
Influenza indications, or household contacts 1 annual dose
of persons with indications 2 Diabetes, heart disease,
chronic pulmonary disease,
chronic liver disease, B C D
including chronic alcoholism
1 dose for unvaccinated persons 3
Pneumococcal 1 dose for persons with medical or other indications. (1 dose
(polysaccharide) revaccination for immunosuppressive conditions) 3,4
1 dose revaccination 4
Congenital immunodeficiency,
leukemia, lymphoma,
generalized malignancy,
Hepatitis B* 3 doses (0, 1-2, 4-6 months) for persons with medical, behavioral, occupational, or other indications 5 therapy with alkylating agents, E F
antimetabolites, radiation
or large amounts
of corticosteroids
Hepatitis A 2 doses (0, 6-12 months) for persons with medical, behavioral, occupational, or other indications 6

Renal failure / end stage renal

1 dose if measles, mumps, or
rubella vaccination history is
Measles, Mumps, unreliable;
Rubella (MMR)* 2 doses for persons with
occupational, geographic,
or other indications 7
Varicella*
disease, recipients of E G
hemodialysis or clotting
factor concentrates
Asplenia including elective
splenectomy and E, H, I
terminal complement
2 doses (0, 4-8 weeks) for persons who are susceptible8 component deficiencies

Meningococcal
1 dose for persons with medical or other indications 9 HIV infection E, J K
(polysaccharide)

See Footnotes for Recommended Adult Immunization Schedule on the back cover. *Covered by the Vaccine Injury Compensation Program.
36
*Covered by the Vaccine Injury Compensation Program. For information on how to file a claim call 1-800-338-2382. Please also visit http://www.hrsa.osp.gov/vicp accessed A. If pregnancy is at 2nd or 3rd trimester during influenza season. G. Hemodialysis patients: Use special formulation of vaccine (40 ug/mL) or two 1.0
February 21, 2002. To file a claim for vaccine injury write: U.S. Court of Federal Claims, 717 Madison Place, N.W., Washington D.C. 20005. (202) 219-9657. B. Although chronic liver disease and alcoholism are not indicator mL 20 ug doses given at one site. Vaccinate early in the course of renal disease.
 Bacterial Diseases

• Control - Elimination as a Public Health Problem

– Pertussis
– Neonatal tetanus
– Congenital syphilis
– Trachoma
– Tuberculosis
– Leprosy
• Eradicable- Regional/Global
– Diphtheria
– Hemophilus influenza b

37
 Viral Diseases

Control - Elimination as a Public Health Problem

Hepatitis B
Hepatitis A
Yellow fever
Rabies
Japanese encephalitis

Eradicable- Regional/Global
Poliomyelitis
Measles
Rubella
Mumps
Varicella
38
 Non Infectious Disease

Control - Elimination as a PH Problem

– Iodine deficiency
“The interaction between
– Vitamin A deficiency nutritional status and infection
– Folic acid deficiency suggests that efforts to
eradicate particular infectious
– Iron deficiency diseases will be strengthened
– Lead poisoning by efforts to eliminate specific
– Silicosis micronutrient deficiencies.”

– Protein energy malnutrition

– Micronutrient malnutrition

Source: Global Disease Elimination and Eradication as Public Health Strategies: Proceedings39of a
Conference Atlanta, Georgia, USA, 1998. Bull WHO. 1998;76 Supplement 2:1-161
 WHO on New Vaccines, 2006
Six traditional vaccines against tuberculosis (BCG),
diphtheria, tetanus, pertussis, polio (OPV) and measles for
their regular infant immunization schedule have contributed
to the prevention of millions of unnecessary deaths.
Many vaccines exist and are increasingly offered to all
infants in many countries allowing for additional prevention
of untimely deaths and disabilities.
Those include vaccines against yellow fever, rubella, hepatitis
B, invasive haemophilus influenzae type b (Hib) disease and
Japanese encephalitis.
In order to achieve the Millennium Development Goal of
reducing child mortality, the expanded use of those new
vaccines will be necessary.

40
 New Vaccines-New Issues

• Pneumcoccus
• Lyme disease
• Rotavirus
• Human Papilloma Virus • Western Equine
Encephalitis
• HIV
• Malaria • Ebola virus
• Dengue • Leishmaniasis
• Salmonella • Helicobacter pylori
• Eschericia coli • Many others

41
 Vaccination and Decline of Hib diseases
in Finland
200 1986- Vaccination
PRP-D, PRP-CRM, PRP-T
180
160
Number of cases

140
120 0-4yr
100 olds
80 >=5 yr
60 olds
40
20
0
8

82

2
6

88
84

86

6
80

90

9
7

9
19

19

19

19
19

19

19

19

19
19

19

Year 42
 % of childhood meningitis caused by Hib in
four regions in Russia (Oct 1996 - Nov 1997)*

Lunina E, 2003
50%

40%

Moscow
30%
St Petersburg
Ekaterinburg
20% 50%
31% 36% 30% Arkhangelsk
10%

0%

*Source: Diomina AA et al, J Microbiol [Russian],1998 43

 Hib in Russia
• H influenza b important and deadly disease of children<5 yrs
• Vaccines since 1987 are effective in preventing disease and
creating herd immunity
• Studies in Europe and in developing countries show high
benefit/cost ratio
• In low birth rate countries, protecting newborns is of
especially high priority
• Studies show Hib needed in Russia
• Russia should adopt Hib vaccine as soon as possible
• New vaccines coming regularly e.g. Hep B and A, pneumonia,
varicella
• Evidence based public health!

Lunina E (Tver), Presentation in Braun SPH 2006 44

 Human Papilloma Virus
• Screening (Pap smears) effective, but expensive and
non-existent in many countries
• HPVs cause cancer of cervix
• Cancer of cervix among top cancers of women
• Sexually transmitted disease
• High prevalence of HPV in uncircumcised men
• Vaccine preventable cancer for primary prevention
• Women’s health issue
• HPV vaccine approved in 2006, now widely used for
11-12 year old girls; ready for wider use
• Must continue Pap smear testing
45
 Helicobacter Pylori
• H. pylori among commonest bacterial infections in humans,
and may be transmitted by water, food via oral fecal route
• Cause of peptic ulcers and cancer of stomach
• Discovered in 1982 by Warren and Marshall
• Genomics may help development of new therapies, including
specific antimicrobial agents and vaccines
• Enormous progress in studying the virulence factors of H.
pylori and their variation, but not yet in clinical practice
• Px and Rx vaccination have been successful in animal models,
but the translation to human vaccine remains difficult
• Vaccine likely in next 5 years; needed to prevent infection in
areas of the world with high prevalence of chronic infection

Marshall and Warren Nobel Prize in Medicine 2005 46

 Bioterrorism and Vaccines

• Anthrax
• Smallpox
• Tularemia
• Hemorrhagic fevers e.g. Rift Valley Fever, others
• Polio
CDC. Biological and Chemical
Terrorism: Strategic Plan for
Preparedness and Response
Recommendations of the CDC
NEJM. 2002;346:1262-1263 Strategic Planning Workgroup.
Smallpox and Bioterrorism MMWR. 2000;49 (RR04)1-14.

47
SAGE on Haemophilus influenza b (Hib)

48
WER Nov 24, 2006
Influenza Vaccine

49
 Current Policy Considerations
• BCG – for infants only (if at all)
• Varicella – to eradicate
• MMR to eradicate measles, mumps and rubella
and rubella syndrome
• Haemophilus influenza B recommended
• Hepatitis B with catchup of children, teens,
adults, health workers
• Influenza and pneumonia vaccination for all
children
• Rotavirus vaccine for all children
• Hepatitis A for endemic areas
• Adult diphtheria, pertussis and tetanus
50
WHO/UNICEF

51
52
 Vaccines administered simultaneously:
combination vaccines
• Combination vaccines needed to fill epidemiologic niches
in EPI with, e.g. a measles-yellow fever, a measles-
Japanese encephalitis or a pertussis-based paediatric
combination rabies vaccine
• Other combinations could broaden protection against the
pathogens responsible for meningitis, pneumonia, or
enteric diseases
• Complex of issues – necessity, feasibility, affordability will
determine future combinations of vaccines

Fletcher MA, Fabre P, Debois H, Saliou P. Int J Infect Dis. 2004;8:328-38.

53
 Summary and Conclusions
• Vaccination is cornerstone of NPH
• Infants, children, adolescents, adults
• Others – health workers, military, prisoners, IDUs, CSWs
• Rapidly developing field
• First priority in public health after safe water and food
• National programs under continuous review, revised annually
• Delivery system may exist, while policy lags behind
• Semashko health system Sanipeds with proven competence
• Combinations safe, cheaper and more effective
• Combine with vitamin and mineral supplementation, bednets
• Should be top priority - save the children
• Compliance and fear
• Political and public support is crucial
54
 Key References
Tulchinsky and Varavikova. The New Public Health chapter 4
CDC. Recommended Childhood and Adolescent Immunization Schedule -
-- United States, 2006. Harmonized Childhood and Adolescent
Immunization Schedule, 2006. MMWR. 2006;54(52);Q1-Q4
CDC. Vaccine Preventable Deaths and the Global Immunization Vision
and Strategy, 2006—2015. MMWR. 2006 / 55(18);511-15
CDC. Recommended Adult Immunization Schedule --- United States,
October 2005--September 2006. 2005;54(40);Q1-Q4.
WHO/UNICEF. GIVS. Global Immunization Vision and Strategy, 2006-
2015, Geneva, 2006. www.unicef.org and www.who.int/vaccines-
documents/
http://aapredbook.aappublications.org/news/vaccstatus.shtml
http://www.who.int/immunization_delivery/new_vaccines/en/index.html

55
 Key Sources

• CDC Atlanta http://www.cdc.gov/mmwr

• WHO (Euro) Health for All Data Base
http://who.dk/hfadb
• WHO Geneva http://who.int/wer
• American Academy of Pediatrics www.aap.org
• National Immunization Program www.cdc.gov/nip
• UNICEF www.unicef.org

56
57