1. Immunization Ahmed Mandil Prof of Epidemiology KSU College of Medicine

2. Headlines Types of immunity Immunizing agents Immunization process (vaccination) Types of vaccines Effectiveness of vaccines Adverse and side effects Cold Chain Vaccination coverage 2009 H1N1 vaccine 26 December 20152Immunization

3. Types of Immunity Specific defenses Immunity Passive immunityActive immunity Following clinical infection Following subclinical infection Following vaccination Following administration of Immunoglobulin or antiserum Transfer of maternal Antibodies Through milk Transfer of maternal Antibodies Through placenta natural acquired 26 December 20153Immunization

4. Active immunity Resistance developed in response to stimulus by an antigen (infecting agent or vaccine) and is characterized by the production of antibodies by the host. 26 December 20154Immunization

5. Passive immunity Immunity conferred by an antibody produced in another host. It may be acquired naturally or artificially (through an antibody-containing preparation). 26 December 20155Immunization

6. Immunizing agents antiseraimmunuglobulinsvaccines 26 December 20156Immunization

7. Immunoglobulins There are 5 major classes: IgM, IgA, IgG, IgE, IgD. Two types of immunoglobulin preparations are available for passive immunization: Normal human immunoglobulin Specific (hyper-immune) human immunoglobulin 26 December 20157Immunization

8. Antisera or antitoxins These are materials prepared in animals or non human sources such as horses. 26 December 20158Immunization

9. Immunoglobulins and Antisera Human normal immunoglobulin Human specific immunoglobulin Non human Ig (antisera) Hepatitis A Measles Rabies Tetanus Mumps Hepatitis B Varicella Diphtheria Tetanus Gas gangrene Botulism Rabies 26 December 20159Immunization

10. Vaccination Vaccination is a method of giving antigen to stimulate the immune response through active immunization A vaccine is an immuno-biological substance designed to produce specific protection against a given disease. A vaccine is “antigenic” but not “pathogenic”. 26 December 201510Immunization

11. Types of vaccines Live vaccines Attenuated live vaccines Inactivated (killed vaccines) Toxoids Polysaccharide and polypeptide (cellular fraction) vaccines Surface antigen (recombinant) vaccines. 26 December 201511Immunization

12. Live vaccines Live vaccines are made from live infectious agents without any amendment. The only live vaccine is “Variola” small pox vaccine, made of live vaccinia cow- pox virus (not variola virus) which is not pathogenic but antigenic, giving cross immunity for variola. 26 December 201512Immunization

13. Live attenuated (avirulent) vaccines Virulent pathogenic organisms are treated to become attenuated and avirulent but antigenic. They have lost their capacity to induce full- blown disease but retain their immunogenicity. Live attenuated vaccines should not be administered to persons with suppressed immune response due to: leukemia and lymphoma, other malignancies, receiving corticosteroids and anti-metabolic agents, Radiation, pregnancy 26 December 201513Immunization

14. Inactivated (killed) vaccines Organisms are killed or inactivated by heat or chemicals but remain antigenic. They are usually safe but less effective than live attenuated vaccines. The only absolute contraindication to their administration is a severe local or general reaction to a previous dose. 26 December 201514Immunization

15. Toxoids They are prepared by detoxifying the exotoxins of some bacteria rendering them antigenic but not pathogenic. Adjuvant (e.g. alum precipitation) is used to increase the potency of vaccine The antibodies produces in the body as a consequence of toxoid administration neutralize the toxic moiety produced during infection rather than act upon the organism itself. In general toxoids are highly efficacious and safe immunizing agents. 26 December 201515Immunization

16. Polysaccharide and polypeptide (cellular fraction) vaccines They are prepared from extracted cellular fractions e.g. meningococcal vaccine from the polysaccharide antigen of the cell wall, the pneumococcal vaccine from the polysaccharide contained in the capsule of the organism, and hepatitis B polypeptide vaccine Their efficacy and safety appear to be high. 26 December 201516Immunization

17. Surface antigen (recombinant) vaccines It is prepared by cloning HBsAg gene in yeast cells where it is expressed. HBsAg produced is then used for vaccine preparations Their efficacy and safety also appear to be high. 26 December 201517Immunization

18. Examples of vaccines, by type Live vaccines Live Attenuated vaccines Killed Inactivated vaccines ToxoidsCellular fraction vaccines Recombinant vaccines Small pox variola vaccine BCG Typhoid oral Plague Oral polio Yellow fever Measles Mumps Rubella Intranasal Influenza Typhus Typhoid Cholera Pertussis Plague Rabies Salk polio Intra-muscular influenza Japanese encephalitis 2009 H1N1 Influenza Diphtheria Tetanus Meningococcal polysaccharide vaccine Pneumococcal polysaccharide vaccine Hepatitis B polypeptide vaccine Hepatitis B vaccine 26 December 201518Immunization

19. Routes of administration Deep subcutaneous or intramuscular route (most vaccines) Oral route (sabine vaccine, oral BCG vaccine) Intradermal route (BCG vaccine) Scarification (small pox vaccine) Intranasal route (live attenuated influenza vaccine) 26 December 201519Immunization

20. Scheme of immunization Primary vaccination One dose vaccines (BCG, variola, measles, mumps, rubella, yellow fever) Multiple dose vaccines (polio, DPT, hepatitis B) Booster vaccination To maintain immunity level after it declines after some time has elapsed (DT, MMR). 26 December 201520Immunization

21. Applications of active immunization Infants and children expanded immunization program (schedule) Active immunization for adult females Vaccination for special occupations Vaccination for special life styles Vaccination for special environmental situations Vaccinations for special health status persons Vaccinations in travel Vaccines against bioterrorism 26 December 201521Immunization

22. Compulsory (obligatory) vaccination for infants, and booster vaccination for children (Expanded Immunization Program) KSU-MOH schedule of vaccination Situation of children failing to complete childhood vaccination schedule 26 December 201522Immunization

23. Active immunization for adult females MMR vaccine is given in adolescence before or after marriage, but not during pregnancy and has to be before 3 months of conception Tetanus toxoid in pregnancy to prevent tetanus neonatorum in the newborn. In the first pregnancy on the third month and after 1 month. The third dose in the second pregnancy, and the fourth on the third pregnancy with a maximum of 5 doses. If 10 years elapse, and then pregnancy occurs, the doses are given from the start Live attenuated vaccines should not be given during pregnancy. 26 December 201523Immunization

24. Vaccination for special occupations Health care workers: hepatitis B, influenza, MMR, polio Public safety personnel (police, fire fighters) and staff of institutions for the developmentally disabled: hepatitis B, influenza Vets and animal handlers: rabies, plague and anthrax Sewage workers: DT, hepatitis A, polio, TAB Food handlers: TAB Military troops and camp dwellers: pneumococcal, meningococcal, influenza, BCG (for non reactors), tetanus 26 December 201524Immunization

25. Vaccinations for special health status persons Immuno-compromised persons ( Leukemia, lymphoma, HIV, malignancy…) Hemodialysis and transplantation: should receive the following vaccines according to their situation: HBV, Influenza, pneuomococcal vaccines 26 December 201525Immunization

26. Vaccinations in travel Varies according to the country of arrival and departure. Primary vaccine series Continuation of booster doses Specific vaccine according to the country traveled to: TAB, YF, cholera, meningiococcal, pneuomococcal, HIB, influenza, rabies, plague, Japanese encephalitis. Hajj for instance necessitates meningococcal vaccination from all over, and YF from places like south Africa, and cholera from places like India. 26 December 201526Immunization

27. Vaccines against bioterrorism Anthrax Small pox plague 26 December 201527Immunization

28. New approaches Schistosomiasis Cancer HIV/AIDS Malaria 26 December 201528Immunization

29. HAZARDS OF IMMUNIZATION No immune response is entirely free from the risk of adverse reactions or remote squeal. The adverse reactions that may occur may be grouped under the following heads: Reactions inherent to inoculation Reactions due to faulty techniques Reactions due to hypersensitivity Neurological involvement Provocative reactions Others 26 December 201529Immunization

30. Estimated periods of maintained immunity due to vaccines Short period (months): cholera vaccine Two years: TAB vaccine Three to five years: DPT vaccine Five or more years: BCG vaccine Ten years: yellow fever vaccine Solid immunity: measles, mumps, and rubella vaccines. 26 December 201530Immunization

31. Levels of effectiveness Absolutely protective (100%): yellow fever vaccine Almost absolutely protective (99%): Variola, measles, mumps, rubella vaccines, and diphtheria and tetanus toxoids. Highly protective (80-95%): polio, BCG, Hepatitis B, and pertussis vaccines. Moderately protective (40-60%) TAB, cholera vaccine, and influenza killed vaccine. 26 December 201531Immunization

32. The Cold Chain The "cold chain" is a system of storage and transport of vaccines at low temperature from the manufacturer to the actual vaccination site. The cold chain system is necessary because vaccine failure may occur due to failure to store and transport under strict temperature controls. 26 December 201532Immunization

33. The Cold Chain Equipment (1) ( a) Walk in cold rooms: They are located at regional level, meant to store vaccines up to 3 months and serve districts. (b) Deep freezers (300 ltr) and Ice lined Refrigerators: supplied to all districts and the WIC locations to store vaccines. Deep freezers are used for making ice packs and to store OPV and measles vaccines. (c) Small deep freezers and ILR (140 ltr) : One set is provided to PHCs, and Family Planning Centers 26 December 201533Immunization

34. The Cold Chain Equipment (2) (d) Cold boxes: Cold boxes are supplied to all peripheral centers. These are used mainly for transportation of the vaccines. (e) Vaccine carriers: Vaccine carriers are used to carry small quantities of vaccines (16-20 vials) for the out of reach sessions. 4 fully frozen ice packs are used for lining the sides, and vials of DPT, DT, TT and diluents should not be placed in direct contact with frozen ice packs. The carriers should be closed tightly. (f) Ice packs: The ice packs contain water and no salt should be added to it. 26 December 201534Immunization

35. Sensitive Vaccines Among the vaccines, polio is the most sensitive to heat, requiring storage at minus 20 degree C. Vaccines which must be stored in the freezer compartment are : polio and measles. Vaccines which must be stored in the COLD PART but never allowed to freeze are : typhoid, DPT, tetanus toxoid, DT, BCG and diluents 26 December 201535Immunization

36. Vaccination Coverage Vaccination coverage is the percent of at risk or susceptible individuals, or population who have been fully immunized against particular diseases by vaccines or toxoids. To be significantly effective in prevention of disease on mass or community level at least a satisfactory proportion (75% or more) of the at risk population must be immunized. 26 December 201536Immunization

37. Ways of achieving satisfactory immunization coverage Efficient immunization service; urban and rural Health awareness and cooperation of the public Periodic mass immunization campaigns, to cover those who missed regular immunizations Outreach programs in rural and nomad areas, and home visits 26 December 201537Immunization

38. Vaccine surveillance and testing “monitoring vaccine effectiveness” Through: Randomized field trials Retrospective cohort studies Case-control studies Incidence density measures 26 December 201538Immunization

39. Randomized field trials The standard way to measure the effectiveness of a new vaccine introduced. In this type of trial, susceptible persons are randomized into two groups and are then given the vaccine or the placebo The vaccinated and the unvaccinated are followed through the high risk season of the year 26 December 201539Immunization

40. Randomized field trials (cont.) The attack rate (AR) is then determined in each group: AR = Number of ill persons Number of persons exposed to the disease  next the vaccine effectiveness (VE) is calculated: VE = AR (unvaccinated) - AR (vaccinated) AR (unvaccinated) X 100 26 December 201540Immunization

41. Retrospective cohort studies The antigenic variability of influenza virus necessitates frequent (often yearly) changes in the constituents of the vaccine to keep them up date with the new strains. Retrospective cohort studies are thus done to evaluate the protective efficacy of the vaccines. 26 December 201541Immunization

42. 2009 H1N1 Flu Vaccine Available types (inactivated, nasal spray) Target groups (pregnant, care-givers for under 6 months, health professionals, 6 months – 24 year olds, at risk 35-64 year olds) Vaccine effectiveness Side effects Who should NOT be vaccinated (allergy from chicken eggs, history of GBS, < 6 months of age, moderate to severe illness with fever) 26 December 2015Immunization42

43. Further Reading Porta M. A dictionary of epidemiology. Fifth Edition. Oxford, New York: Oxford University Press, 2008. WHO. State of the World's Vaccines and Immunization. Third Edition. World Health Organization, 2009 Salama R. Immunization. Community Medicine. Ismailiah: Suez Canal University. CDC. Key Facts about 2009 H1N1 Influenza vaccine. http://www.cdc.gov/h1n1flu/vaccination/vaccine_keyfacts.htm http://www.cdc.gov/h1n1flu/vaccination/vaccine_keyfacts.htm (accessed on 31 Oct, 2009) CDC. Vaccine safety. http://www.cdc.gov/h1n1flu/vaccination/vaccine_safety _qa.htm (accessed on 31 Oct, 2009) http://www.cdc.gov/h1n1flu/vaccination/vaccine_safety _qa.htm 26 December 201543Immunization