Transcript Vaccination: A Cornerstone of Public Health

Vaccination: A Cornerstone of
Public Health
TH Tulchinsky MD MPH
Braun School of Public Health
Dec 2008
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Licensed Vaccines in Routine Use in the United States, 1980 and 2008
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Smith, J. C. et. al. Ann Intern Med 2009;150:45-49
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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: WB
Saunders, 1988 [Introduction].
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Millennium Development Goals
2015
1.
2.
3.
4.
5.
6.
7.
8.
Cut poverty by half ($1/day)
Universal Primary Education
Gender equality in education
Cut Infant Mortality and <5 MR by 2/3rds
Reduce maternal MR 75%
Reduce HIV/AIDS & malaria
Sustainable environment
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
After World War II
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• 1955 Injectable Polio
Vaccine (IPV)
• 1962 Oral Polio Vaccine
(OPV)
• 1964 Measles
• 1967 Mumps
• 1970 Rubella
• 1981 Hepatitis B
1798
1885
1897
1923
1926
1927
1927
1935
Smallpox
Rabies
Plague
Diphtheria
Pertussis
Tuberculosis (BCG)
Tetanus
Yellow Fever
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
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Political support
Professional recognition
Financing
Expanding vaccine
capability
• Organization, delivery,
follow up
• Reporting “up and down
and sideways” (UDS)
• Program content
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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
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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 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.”
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
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Tetanus incidence per 100000
0.3
0.25
0.2
Denmark
Israel
Russian Federation
United Kingdom
Uzbekistan
0.15
0.1
0.05
0
1970
20
1980
1990
2000
2010
Pertussis incidence per 100000
400
300
Denmark
Denmark
Israel
Russian Federation
United Kingdom
Uzbekistan
200
UK
100
0
1970
21
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
1980
22
1985
1990
1995
2000
2005
2010
Rubella incidence per 100000
1000
Israel
900
800
700
UK
600
Denmark
Israel
Russian Federation
United Kingdom
Uzbekistan
500
400
300
200
100
0
1970
23
1980
1990
2000
2010
Diphtheria incidence per 100000
30
25
Russia
20
Israel
Russian Federation
Turkey
United Kingdom
Uzbekistan
15
10
5
0
1970
24
1980
1990
2000
2010
Tuberculosis incidence per 100000
100
Russia
90
80
Uzbekistan
70
60
Israel
Russian Federation
Turkey
United Kingdom
Uzbekistan
50
40
Turkey
30
20
UK
10
0
1970
Israel
1980
1990
2000
2010
25
Viral hepatitis B incidence per 100000
50
40
30
Finland
Israel
Russian Federation
United Kingdom
20
Russia
10
0
1985
26
1990
1995
2000
2005
2010
Hospital discharges, infectious and
parasitic diseases per 100000
1500
1000
Finland
Israel
Russian Federation
United Kingdom
500
0
1985
27
1990
1995
2000
2005
2010
Clinically diagnosed AIDS incidence per 100000
4
3
Finland
Israel
Russian Federation
United Kingdom
2
1
0
1970
28
1980
1990
2000
2010
Haemophilius influenza type b invasive
disease incidence per 100000
2.5
2
1.5
Finland
Israel
Russian Federation
United Kingdom
1
0.5
0
1990
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1995
2000
2005
2010
CDC Recommended Immunization Schedule,
0 to 6 years, US, 2009
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WHO 1998 Targets of Infectious Disease
Eradication / Control
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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
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on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report. 2005;54(RR);1-40
Infant, Child and Adolescent
Immunization Schedule US CDC, MMWR. 2006
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Recommended Adult Immunization Schedule, United States, 2002-2003
For all persons in this
age group
Age
Vaccine
Catch-up on
childhood vaccinations
19-49 years
For persons with
medical / exposure indications
50-64 years
Tetanus, Diphtheria
(Td)*
Recommended Immunizations for Adults with Medical Conditions, United States, 2002-2003
For all persons in
this group
Catch-up on
childhood vaccinations
Vaccine
65 years and older
Medical
Conditions
1 dose booster every 10 years1
TetanusDiphtheria
(Td)*
Pregnancy
Influenza
Pneumococcal
(polysaccharide)
1 dose annually for persons
with medical or occupational
indications, or household contacts
of persons with indications 2
1 annual dose
1 dose for persons with medical or other indications. (1 dose
revaccination for immunosuppressive conditions) 3,4
1 dose for unvaccinated persons 3
1 dose revaccination 4
Hepatitis B*
3 doses (0, 1-2, 4-6 months) for persons with medical, behavioral, occupational, or other indications 5
Hepatitis A
2 doses (0, 6-12 months) for persons with medical, behavioral, occupational, or other indications 6
Measles, Mumps,
Rubella (MMR)*
Varicella*
Meningococcal
(polysaccharide)
1 dose if measles, mumps, or
rubella vaccination history is
unreliable;
2 doses for persons with
occupational, geographic,
or other indications 7
2 doses (0, 4-8 weeks) for persons who are susceptible8
1 dose for persons with medical or other indications 9
Diabetes, heart disease,
chronic pulmonary disease,
chronic liver disease,
including chronic alcoholism
Influenza
For persons with
medical / exposure indications
Pneumo- Hepatitis
coccal
B*
(polysaccharide)
B
C
E
Renal failure / end stage renal
disease, recipients of
hemodialysis or clotting
factor concentrates
E
HIV infection
See Footnotes for Recommended Adult Immunization Schedule on the back cover.
*Covered by the Vaccine Injury Compensation Program.
*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
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.
A. If pregnancy is at 2nd or 3rd trimester during influenza season.
B. Although chronic liver disease and alcoholism are not indicator
Measles
Mumps
Rubella
(MMR)*
Varicella*
A
Congenital immunodeficiency,
leukemia, lymphoma,
generalized malignancy,
therapy with alkylating agents,
antimetabolites, radiation
or large amounts
of corticosteroids
Asplenia including elective
splenectomy and
terminal complement
component deficiencies
Hepatitis
A
Contraindicated
D
F
G
E, H, I
E, J
K
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G. Hemodialysis patients: Use special formulation of vaccine (40 ug/mL) or two 1.0
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
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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
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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
micronutrient deficiencies.”
Silicosis
Protein energy malnutrition
Micronutrient malnutrition
Source: Global Disease Elimination and Eradication as Public Health Strategies: Proceedings39
of 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.
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New Vaccines-New Issues
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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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1986- Vaccination
PRP-D, PRP-CRM, PRP-T
0-4yr
olds
Year
6
19
9
4
19
9
2
19
9
19
82
19
84
19
86
19
88
19
90
19
80
8
>=5 yr
olds
19
7
6
200
180
160
140
120
100
80
60
40
20
0
19
7
Number of cases
Vaccination and Decline of Hib diseases
in Finland
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% of childhood meningitis caused by Hib in
four regions in Russia (Oct 1996 - Nov 1997)*
Lunina E, 2003
50%
40%
30%
20%
31%
50%
36%
30%
Moscow
St Petersburg
Ekaterinburg
Arkhangelsk
10%
0%
*Source: Diomina AA et al, J Microbiol [Russian],1998
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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
NEJM. 2002;346:1262-1263
Smallpox and Bioterrorism
CDC. Biological and Chemical
Terrorism: Strategic Plan for
Preparedness and Response
Recommendations of the CDC
Strategic Planning Workgroup.
MMWR. 2000;49 (RR04)1-14.
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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 measlesJapanese 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
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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 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, 20062015, Geneva, 2006. www.unicef.org and www.who.int/vaccinesdocuments/
http://aapredbook.aappublications.org/news/vaccstatus.shtml
http://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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