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OBJECTIVES

Immunization “The most important investment that any country can make in the health of its’ children”. OBJECTIVES. 1 Outline the important contribution that vaccination can make to World Health. 2 Briefly describe the principles and basis of immunization.

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OBJECTIVES

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  1. Immunization “The most important investment that any country can make in the health of its’ children”

  2. OBJECTIVES • 1 Outline the important contribution that vaccination can make to World Health. • 2 Briefly describe the principles and basis of immunization. • 3 Discuss the different types of vaccine, their advantages and disadvantages • 4 Explain common vaccine strategies for children and adults including examples of important vaccines.

  3. Rationaleof Immunization • Objective: to produce, without harm to the recipient, a degree of resistance sufficient to prevent a clinical attack of the natural infection and to prevent the spread of infection to susceptibles in the community. • Personal gain and public health benefit • Degree of resistance may not protect against an overwhelming challenge, but exposure may help to boost immunity

  4. Adjuvant Adverse reaction Antitoxin Immunization Active Passive Immunoglobulin e.g., Human Normal Immunoglobulin [HNIG] Human Specific Immunoglobulin / Hyperimmune globulin Toxoid modified bacterial toxin Definitions

  5. Definitions • Vaccine • a suspension of live attenuated or inactivated microorganisms or fractions thereof administered to induce immunity and thereby prevent infectious disease • Vaccination • the term used to refer to the administration of any vaccine or toxin

  6. Principles of Immunization • Immunization denotes the process of inducing or providing immunity artificially • Protection from infectious disease • Usually indicated by the presence of antibody • Very specific to a single antigen

  7. Principles of Immunization Antigen • A live or inactivated substance (e.g., protein, polysaccharide) capable of producing an immune response Antibody • Protein molecules (immunoglobulin) produced by B lymphocytes to help eliminate an antigen

  8. Principles of Immunization Active • Protection produced by the person's own immune system, “usually” permanent • Immunity and immunologic memory produced, similar to the natural infection but without the risk of disease Passive • Protection transferred from another person or animal as antibody • This will afford temporary protection • In infancy, transplacental transfer is the most important source

  9. Sources of Passive Immunity • Almost all blood or blood products • Homologous pooled human antibody (immune globulin) • Homologous human hyperimmune globulin • Heterologous hyperimmune serum (antitoxin)

  10. Example: Antibody for Prevention of Respiratory Syncytial Virus infection • RSV-IGIV • Human hyperimmune globulin • Contains other antibodies • Palivizumab (“Synagis”) • Mouse monoclonal • Contains only RSV antibody

  11. Classification of Vaccinesviral or bacterial • Live attenuated • single dose e.g., BCG (related org, shared antigens) • two doses if immunity likely to wane over time, e.g., rubella, measles • three doses for a different reason: oral polio in primary schedule because there are 3 serotypes of poliovirus • Inactivated • multiple doses; a course typically consists of 3 doses, +/- a subsequent booster • primary response, secondary response

  12. Live vaccine • Attenuated agent (unstable) • Amplification of response - gradual rise to peak response then decline • Variable but “long” duration of immunity -the immune response produced is similar to that produced by the natural infection • There will be a booster effect with subsequent exposure • There is a possibility of generalised /severe infection in an immunocompromised individual • There may be interference from circulating antibody with the “take” of the vaccine

  13. Inactivated Vaccines Whole • virus • bacteria • protein-based • subunit • toxoid • polysaccharide-based • pure • conjugate

  14. Inactivated Vaccines • Cannot replicate • There will be minimal interference from circulating antibody • In general they are not as effective as live vaccines • Generally require 3-5 doses • The immune response produced is mostly humoral • Antibody titer falls over time

  15. Viral measles, mumps, rubella, vaccinia, varicella, yellow fever, oral polio, rotavirus, (influenza “Flumist”, not available outside USA at present) Bacterial BCG (oral typhoid) Viral polio, hepatitis A, rabies, influenza Bacterial (whole cell)pertussis, typhoid, (cholera), (plague) Examples of live and inactivated vaccines Live Inactivated

  16. Inactivated Vaccines Fractional vaccines • Subunithepatitis B, influenza, acellular pertussis, (typhoid Vi), (Lyme) • Toxoiddiphtheria, tetanus

  17. Polysaccharide Vaccines:Derived from bacterial capsule • pneumococcal • meningococcal • Haemophilus influenzae type b (“New”) Conjugate polysaccharide vaccines • Haemophilus influenzae type b • meningococcal • pneumococcal

  18. Pure Polysaccharide Vaccines • Not consistently immunogenic in children <2 years of age • No booster response • Produce antibody with less functional activity than that produced by the infection • Immunogenicity is greatly improved by conjugation

  19. Addition of 7-valent pneumococcal vaccine to routine schedule of immunisations Children who attended hopitals in the greater Dublin area, 2002-2004 Incidence of invasive pneumococcal disease: 10.6/100,000 - 2 deaths 61.4% <2 years; 76% < 5 years Reduced penicillin susceptibility in 15% - all were vaccine serotypes Based on serotype data, in paediatric patients PCV7 would prevent <90% of cases of sepsis, <82.5% meningitis, <59% pneumonia A safe and effective vaccine to be added to the infant schedule Fitzsimons JJ, Chong AL, Cafferkey MT, Butler K. Ir J Med Sci 2008;177:225-31

  20. PCV7 would be cost effective Implementing a PCV7 vaccine programme with a birth cohort of 61,000, would be expected to prevent 7703 cases of pneumococcal infection over 5 years – costs avoided €2.05mi rising to €4.6mi allowing for the effect of herd immunity Economic evaluation of a universal childhood pneumococcal conjugate vaccination strategy in Ireland Tilson L, Usher C, Butler K, Fitzsimons J, O’Hare F, Cotter S, O’Flanagan D, Johnson H, Barry M Value Health 2008;May 16 [Epub ahead of print]

  21. The need for a vaccine is determined by the morbidity and mortality from the natural infection e.g., Contrast measles, rubella & hepatitis B

  22. Morbidityin 10% Otitis Media 5% RTI 4% Convulsions 0.5% Other neurological 0.1% Hospital Admission 1.4% Very small risk of SSPE 1 in 300,000 cases Mortality Notifications 2,161,542 Deaths 365 Mortality Rate per 100,000 notified cases 16.9 England & Wales, 1970 to 1988 Measles: Morbidity & Mortality

  23. Morbidity“benign illness” children thrombotic thrombocytopenic purpura 1 in 500 Adults: acute polyarticular arthropathy women > men chronic arthritis may occasionally develop Neurological postinfectious encephalopathy and encephalitis 1 in 4,700 to 1 in 6,000 Mortality due to the neurologic manifestations[20-50% of patients with these] Rubella: Morbidity & Mortality Principal morbidity: Congenital Rubella Syndrome

  24. Morbidity Up to 90% of vertically infected infants may become chronic carriers Between 2-20% of infected adults become chronic carriers Carriers may develop chronic hepatitis, cirrhosis or hepatocellular carcinoma Mortality approximately 1% of those hospitalised with acute HBV infection die superinfection with delta agent [hepatitis D] may lead to fulminant liver failure HBV infection is a major economic burden worldwide Hepatitis B: Morbidity & Mortality

  25. Immunization: Protection of • infantsagainst the important infectious diseases of childhood (early) • adults and childrenagainst the infectious hazards of travel (timely) • susceptible or “at risk” adults and children • adultsagainst certain infections that may be acquired at work

  26. HERD IMMUNITY • When most people in community are immune to a particular infection that is spread from person to person, the natural transmission of the infection is effectively inhibited • Vaccine uptake rates >90% (measles 95%) • Not tetanus!

  27. Routine immunisation schedule from 1st September 2008

  28. Recommended changes to routine immunisation schedule, 2008 Pneumococcal conjugate vaccine into primary schedule (2 + 1) Hepatitis B vaccine into primary schedule (3) Hib and MenC boosters in 2nd year of life Hib to remain at 3 + 1 MenC to be 2 + 1 Td booster for 11-14 years change to Tdap ?10- 12yrs girls HPV (0, 1, 6 months)

  29. Geographical variation • diphtheria booster for adults • travellers to an endemic area • d not D • IPV versus OPV • inclusion of Hepatitis B in the routine childhood immunization schedule • Varicella-zoster in routine infant schedule in some countries

  30. Adult immunizations 1Normal Adults • Women seronegative for rubella • rubella • Previously non-immunised individuals • tetanus • Individuals in specific high risk groups • HBV, HAV, influenza, pneumococcal • Those travelling abroad • hepatitis A, typhoid, (polio)

  31. Hepatitis B [Hepatitis A] Tuberculosis Influenza immunise those involved in the long term care of the elderly Check in some clinical circumstances varicella immunity rubella antibody measles antibody polio booster to some e.g., laboratory staff performing faecal cultures Adult Immunizations 2Health Care Workers

  32. Immunization Interrupted immunization course • resume as soon as possible; it is not necessary to repeat the course Late primary immunization • immunise as soon as possible • DTaP/IPV/Hib, menC and MMR may be given simultaneously; • the number of Hib doses depends on the child’s age

  33. The following reactions to a vaccine are contraindications to a further dose • anaphylaxis • fever > 40.5oC • within 48 hours of vaccine administration for which no other cause is found • Any of the following occurring within 72 hours of vaccine administration: • prolonged unresponsiveness • prolonged inconsolable or high-pitched screaming for > 4 hr • convulsions or encephalophathy

  34. Vaccines & pregnancy • Live vaccines should generally not be administered in pregnancy because of the theoretical possibility of harm to the foetus • [However when there is a significant risk of exposure to poliomyelitis (e.g., travel to an endemic area) the need for immunization outweighs any possible risk to the foetus] • Some inactivated vaccines are/may be administered in pregnancy e.g., tetanus toxoid

  35. Complications and side-effects • Virulent infectious material in the vaccine • allergic reactions • toxicity harmful effects on the foetus • harmful effects on immunodeficient hosts • Other effects • [Suggested effects without substantiation • MMR - link with autism & with Crohn’s Disease]

  36. Specific examples of immunisation strategies

  37. measles

  38. rubella

  39. Hepatitis B

  40. Hepatitis B • Chronic HBV infection with persistence of HBsAg occurs in • up to 90% of infants infected vertically, • 30% of children 1 to 5 years old infected after birth • in 5 to 10% of older children, adolescents and adults with hepatitis B infection

  41. HBV: Perinatal Transmission • Babies of carrier mothers should receive HB vaccine +/- hepatitis B hyperimmune globulin (HBIG) • Many countries now include routine neonatal HBV immunization in the routine schedule

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