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Vaccination: A Cornerstone of Public Health

TH Tulchinsky MD MPH

Braun School of Public Health

Dec 2008

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Smith, J. C. et. al. Ann Intern Med 2009;150:45-49

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

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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

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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: WBSaunders, 1988 [Introduction].

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Millennium Development Goals2015

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

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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.

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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.

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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

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Introduction of first generation of vaccines for use in humans

Originals

• 1798   Smallpox • 1885   Rabies • 1897   Plague • 1923   Diphtheria • 1926   Pertussis • 1927   Tuberculosis (BCG) • 1927   Tetanus • 1935    Yellow Fever

After World War II

• 1955   Injectable Polio Vaccine (IPV)

• 1962   Oral Polio Vaccine (OPV)

• 1964   Measles • 1967   Mumps • 1970   Rubella • 1981   Hepatitis B

Plotkin SA, Mortimer EA

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Vaccines used by the Expanded Programme on Immunization (EPI)

From 1974 onwards •   BCG •   Polio •   DTP •   Measles*

Added later •   Yellow Fever (in

endemic countries) •   Hepatitis B •   MMR used in

industrialized countries and now in many developing countries

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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

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Vaccination Issues

• Political support

• Professional recognition

• Financing

• Expanding vaccine capability

• Organization, delivery, follow up

• Reporting “up and down and sideways” (UDS)

• Program content

• Strategies

• Select target groups

• Coverage

• Herd immunity

• Cold chain and logistics

• Continuous up-dating

• International and “gold standards”

• Infectious and chronic diseases

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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

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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

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“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.”

BMJ  2006;333:11 (1 July).

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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

200

0.05

0.1

0.15

0.2

0.25

0.3

1970 1980 1990 2000 2010

DenmarkIsraelRussian FederationUnited KingdomUzbekistan

Tetanus incidence per 100000

210

100

200

300

400

1970 1980 1990 2000 2010

DenmarkIsraelRussian FederationUnited KingdomUzbekistan

Pertussis incidence per 100000

Denmark

UK

220

0.05

0.1

0.15

1980 1985 1990 1995 2000 2005 2010

DenmarkIsraelRussian FederationUnited KingdomUzbekistan

Congenital rubella incidence per 100000

UK

IsraelDenmark

230

100

200

300

400

500

600

700

800

900

1000

1970 1980 1990 2000 2010

DenmarkIsraelRussian FederationUnited KingdomUzbekistan

Rubella incidence per 100000

UK

Israel

240

5

10

15

20

25

30

1970 1980 1990 2000 2010

IsraelRussian FederationTurkeyUnited KingdomUzbekistan

Diphtheria incidence per 100000

Russia

250

10

20

30

40

50

60

70

80

90

100

1970 1980 1990 2000 2010

IsraelRussian FederationTurkeyUnited KingdomUzbekistan

Tuberculosis incidence per 100000

Russia

Uzbekistan

Turkey

UK

Israel

260

10

20

30

40

50

1985 1990 1995 2000 2005 2010

FinlandIsraelRussian FederationUnited Kingdom

Viral hepatitis B incidence per 100000

Russia

270

500

1000

1500

1985 1990 1995 2000 2005 2010

FinlandIsraelRussian FederationUnited Kingdom

Hospital discharges, infectious and parasitic diseases per 100000

280

1

2

3

4

1970 1980 1990 2000 2010

FinlandIsraelRussian FederationUnited Kingdom

Clinically diagnosed AIDS incidence per 100000

290

0.5

1

1.5

2

2.5

1990 1995 2000 2005 2010

FinlandIsraelRussian FederationUnited Kingdom

Haemophilius influenza type b invasive disease incidence per 100000

CDC Recommended Immunization Schedule, 0 to 6 years, US, 2009

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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

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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

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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

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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 on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2005;54(RR);1-40

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Infant, Child and Adolescent Immunization Schedule US CDC, MMWR. 2006

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Bacterial Diseases

• Control - Elimination as a Public Health Problem

– Pertussis

– Neonatal tetanus

– Congenital syphilis

– Trachoma

– Tuberculosis

– Leprosy

• Eradicable- Regional/Global

– Diphtheria

– Hemophilus influenza b

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Viral Diseases

Control - Elimination as a Public Health ProblemHepatitis BHepatitis AYellow feverRabiesJapanese encephalitis

Eradicable- Regional/Global PoliomyelitisMeaslesRubellaMumpsVaricella

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Non Infectious Disease

Control - Elimination as a PH Problem

– Iodine deficiency

– Vitamin A deficiency

– Folic acid deficiency

– Iron deficiency

– Lead poisoning

– Silicosis

– Protein energy malnutrition

– Micronutrient malnutrition

“The interaction between nutritional status and infection suggests that efforts to eradicate particular infectious diseases will be strengthened by efforts to eliminate specific micronutrient deficiencies.”

Source: Global Disease Elimination and Eradication as Public Health Strategies: Proceedings of a Conference Atlanta, Georgia, USA, 1998. Bull WHO. 1998;76 Supplement 2:1-161

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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.

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New Vaccines-New Issues

• Pneumcoccus• Rotavirus • Human Papilloma Virus• HIV• Malaria• Dengue• Salmonella• Eschericia coli

• Lyme disease• Western Equine

Encephalitis• Ebola virus• Leishmaniasis• Helicobacter pylori• Many others

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Vaccination and Decline of Hib diseases in Finland

020406080

100120140160180200

Year

Num

ber

of ca

ses

0-4yrolds

>=5 yrolds

1986- Vaccination PRP-D, PRP-CRM, PRP-T

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

31% 50% 36% 30%

0%

10%

20%

30%

40%

50%

MoscowSt PetersburgEkaterinburgArkhangelsk

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

Lunina E, 2003

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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

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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

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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

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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 Strategic Planning Workgroup. MMWR. 2000;49 (RR04)1-14.

NEJM. 2002;346:1262-1263 Smallpox and Bioterrorism 

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SAGE on Haemophilus influenza b (Hib)

WER Nov 24, 2006

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Influenza Vaccine

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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

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WHO/UNICEF

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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.

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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

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Key References

Tulchinsky and Varavikova. The New Public Health chapter 4CDC. 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.shtmlhttp://www.who.int/immunization_delivery/new_vaccines/en/index.html

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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

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