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
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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 4
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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]. 7
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 2/3 rds Reduce maternal MR 75% Reduce HIV/AIDS & malaria Sustainable environment 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 • • • 1955 Injectable Polio Vaccine (IPV) • 1962 Oral Polio Vaccine (OPV) • 1964 Measles • 1967 Mumps • 1970 Rubella • 1981 Hepatitis B 1798 Smallpox 1885 Rabies 1897 Plague 1923 Diphtheria 1926 Pertussis 1927 Tuberculosis (BCG) 1927 Tetanus 1935 Yellow Fever Plotkin SA, Mortimer EA 12
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 13
Vaccine Preventable Diseases (VPDs) • World immunization coverage up from 10% in 1970 s to 80% in 1990 s, 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 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 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 Glaxo. Smith. Kline 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). 18
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 - d. T, MMR • Teen agers – catch up Hep B, MMR • Adult women - Rubella • Chronically ill – Influenza, pneumococcal pneumonia • Travelers – yellow fever, polio, d. T • Adults - d. T • Elderly - Influenza, pneumococcal pneumonia, d. T • Risk groups for bioterrorism – smallpox, anthrax 19
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Denmark UK 21
Denmark Israel UK 22
Israel UK 23
Russia 24
Russia Uzbekistan Turkey UK Israel 25
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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
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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 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 micronutrient deficiencies. ” Silicosis Protein energy malnutrition Micronutrient malnutrition Source: Global Disease Elimination and Eradication as Public Health Strategies: Proceedings of a 39 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 Rotavirus Human Papilloma Virus HIV Malaria Dengue Salmonella Eschericia coli • Lyme disease • Western Equine Encephalitis • Ebola virus • Leishmaniasis • Helicobacter pylori • Many others 41
Vaccination and Decline of Hib diseases in Finland 1986 - Vaccination PRP-D, PRP-CRM, PRP-T 42
% of childhood meningitis caused by Hib in four regions in Russia (Oct 1996 - Nov 1997)* Lunina E, 2003 *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 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 (RR 04)1 -14. 47
SAGE on Haemophilus influenza b (Hib) WER Nov 24, 2006 48
Influenza Vaccine 49
Current Policy Considerations • BCG – for infants only (if at all) • Varicella – to eradicate • MMR to eradicate measles, mumps 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
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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. 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); Q 1 -Q 4 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); Q 1 -Q 4. 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 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
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