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31/5/2023 Learning Outcomes • Importance of vaccines Principles of Immunization Malaysian Immunization Schedule • How vaccine works • Active and passive immunization • Types & route of administration of vaccines • Adverse reactions and contraindications of vaccines • National Immunization Program...

31/5/2023 Learning Outcomes • Importance of vaccines Principles of Immunization Malaysian Immunization Schedule • How vaccine works • Active and passive immunization • Types & route of administration of vaccines • Adverse reactions and contraindications of vaccines • National Immunization Program (Malaysia) 1 2 Why is Immunization Important? Albert Sabin Public Health Measures with Greatest Impact on World’s Health: Clean Water & Vaccines Edward Jenner • Prevent spread of infectious diseases in community • Prevent disabilities and death from infectious diseases • Rapid impact • Expansive reach • Saves money Jonas Salk 3 6 Reported cases of vaccine-preventable diseases worldwide from 1980 to 2020, by disease 21st Century Tuberculosis Pertussis Diphtheria Tetanus Polio Measles 29 vaccine-preventable diseases 9 12 1 31/5/2023 Vaccination Process introducing a vaccine into the body regardless of the development of immunity Adaptive immunity Innate immunity Definitions Epithelial barriers Immunization Development of immunity in the body after vaccine injection Phagocytes B-Lymphocytes Plasma cells Antibodies Dendritic cells T-Lymphocytes Effector T cells APCs Complement NK cells Hours 0 Days 6 12 1 4 7 Time after infection 15 17 Active Immunity Immune Response Primary Immune Response Secondary Immune Response IgG Amount of Antibody Amount of Antibody IgM first antibody to appear IgG IgM 0 7 Exposure to Antigen triggers immune system to produce antibodies to that disease • Natural immunity: acquired from exposure to disease organism through infection Final concentration of IgG higher than in primary immune IgG appears earlier response than in primary immune response • Vaccine-induced immunity: acquired through introduction of a vaccine containing antigens of the disease organism IgM 14 First exposure to Ag 21 28 35 0 7 14 21 28 35 Second exposure to Ag 18 19 Passive Immunity Antigen Substance that is capable of stimulating an immune response A person is given antibodies to a disease rather than producing them through his or her own immune system • Newborn baby acquires antibodies from mother through placenta • Give antibody-containing blood products when immediate protection from a specific disease is needed 20 Whole Organism Tiny Part of Organism 32 2 31/5/2023 Types of Vaccines COVID-19 vaccines Live attenuated (LAV) Subunit (purified antigen) Inactivated Virus S Protein Inactivated (killed antigen) Genetic Material mRNA/DNA Toxoid (inactivated toxins) Viral vector vaccine Nucleic acid vaccine 33 34 Mono and Polyvalent Vaccines Increasing Number of Vaccines Polyvalent Monovalent Single strain of a single Ag ≥2 strains of same Ag Eg: Measles vaccine Eg: Oral polio vaccine (OPV) 35 36 Combination Vaccines Combination Vaccines Contains of ≥2 Ag antigens in the same preparation DPT Diphtheria Pertussis Tetanus 38 39 3 31/5/2023 Hexavalent Vaccine Combination Vaccines: Advantages 1. 2. 3. 4. 5. Diphtheria Pertussis Tetanus Hepatitis B Haemophilus influenzae type B 6. Polio • Fewer injections: Less pain & anxiety • Reduce cost of extra health care visits • Simplified schedule: better compliance; improve timeliness of vaccination • Less preparation time • Reduce cost of stocking & administering separate vaccines • Easier introduction of new vaccines 40 43 Live Attenuated Vaccines Inactivated Whole-Cell Vaccines (Killed Antigen) Contains a weakened (or attenuated) form of the organism that causes a disease. DPT Virus DPT Bacteria Tuberculosis (BCG) Oral polio MMR Rotavirus Varicella Inactivated vaccines are made from microorganisms that have been killed through physical or chemical processes 48 49 Inactivated Whole-Cell Vaccines Bacteria Virus DPT Whole-cell pertussis Typhoid 50 Subunit Vaccines Protein-based Polysaccharide Conjugate Inactivated polio virus Influenza (injectable) Hepatitis A 51 4 31/5/2023 Protein-Based Subunit Vaccines Polysaccharide vaccines Acellular pertussis (aP) vaccines • Contains purified polysaccharide capsules • Poor immune response in children <2 years • Short-term immunity, slow rise of Ab levels, no immune memory • Eg 23-valent pneumococcal polysaccharide vaccine (PPSV23) Inactivated pertussis toxin (protein) Bacterial components Hepatitis B (HepB) vaccines Hepatitis B virus surface antigen (HBsAg) Human papillomavirus (HPV) vaccines Contains virus-like particles (VLP) VLP contain no viral DNA 52 53 Conjugate Subunit Vaccines Nucleic Acid Vaccine Bacteria Meningococcus Haemophilus influenzae type b (Hib) Pneumococcus (PCV10 or PCV13) Polysaccharide conjugated with carrier protein (diphtheria and tetanus toxoid) to induce long-term protective response Generate effective T-cell-dependent Ab response in children <2 years 55 Virus Immune Response Spike Protein Protein Translation Lymphocyte Translated viral S protein Antibody mRNA codes S protein Lipid nanoparticle 62 Viral Vector Vaccine Toxoid Vaccines • Toxin – produced by bacteria (eg tetanus, diphtheria) – invades bloodstream and cause symptoms • Toxoid Protein-based inactivated toxin; used as Ag to elicit immunity • Adjuvants added to increase immune response, (toxoid adsorbed to aluminium or calcium salt) 67 69 5 31/5/2023 Herd immunity Routes of Administration Can’t Vaccinate Intradermal Vaccine Protects an Individual Subcutaneous Intramuscular Vaccine Protects whole community even those who can’t vaccinate Oral 70 Intranasal 77 Intradermal BCG Administration Site of Administration Infants aged <12 months Intramuscular/Subcutaneous Anterolateral Thigh Injection site 82 84 Site of Administration Site of Administration Children aged ≥12 months Intramuscular Deltoid area Children aged ≥12 months Subcutaneous Upper outer triceps of the arm Injection site Right arm under carer’s armpit Left arm restrained 85 86 6 31/5/2023 Adverse Events Following Immunization (AEFIs) Route of Administration Route Intradermal Subcutaneous Intramuscular Vaccine BCG MMR MR Measles Japanese Encephalitis (Imojev) Hepatitis B DTaP-IPV-HBV-Hib PCV10 HPV DT Tetanus 87 • Any untoward medical occurrence which follows immunization (Does not necessarily have a causal relationship with the usage of the vaccine) • Adverse event may be an – unfavourable or unintended sign – abnormal laboratory finding – symptom or disease 88 Adverse events following immunization (AEFI) Vaccine product-related reaction (Limb swelling from DTP vaccination) Vaccine quality defect-related reaction (Failure to inactivate a batch of IPV leading to paralytic polio) Antigens Stabilizers Adjuvants Antibiotics Immunization error-related reaction (Transmission of infection due to a contaminated multidose vial) Components of a Vaccine Immunization anxiety-related reaction (Vasovagal syncope in an adolescent following immunization) Coincidental event (Fever occurs at time of vaccination, but is caused by malaria) Preservatives 91 98 Minor Vaccine product-related reaction • • • • • Severe Vaccine product-related reaction Vaccine BCG Local reaction (pain, swelling, redness) Fever Irritability Malaise Bodyache OPV DTP Measles 100 Reaction Fatal dissemination of BCG infection Vaccine-associated paralytic poliomyelitis Prolonged crying and seizures Hypotonic hyporesponsive episodes Febrile seizures Thrombocytopenia Anaphylaxis Onset 1–12 months 4–30 days 0–24 h 0–24 h 6–12 days 15–35 days 1h 101 7 31/5/2023 Absolute Contraindications to Vaccination • Severe allergic reaction (e.g. anaphylaxis) after a previous dose or to a vaccine component • Encephalopathy (e.g. coma, decreased level of consciousness, or prolonged seizures), not attributable to another identifiable cause, within 7 days of administration of a dose of DTP • Live attenuated vaccine contraindicated in severe immunodeficiency (congenital immunodeficiency, chemotherapy, high dose corticosteroids, stem-cell or solid organ transplant) 109 Conditions Misperceived as contraindications to vaccination • Mild acute illness (URI) • Mild-to-moderate local reaction (i.e. swelling, redness, soreness); mild fever after previous dose • Current antimicrobial therapy • Convalescent phase of illness • Preterm birth (defer HBV if Wt <2 kg • Recent exposure to infectious disease 110 National Immunization Program, Malaysia Malaysian National Immunisation Programme (NIP) Dec 2020 Vaccine Month 0 2020 HPV 2010 2010 MMR Hib 2002 2000 1990 Measles 1982 1980 OPV 1972 1970 1960 1950 111 • History of non-vaccine allergies, relatives with allergies or receiving allergen extract immunotherapy • Family history of seizures, or adverse event after vaccination • Stable neurological condition (e.g. cerebral palsy, wellcontrolled seizures or developmental delay DTwP 1958 Smallpox 1950 BCG 1961 DTwP-Hep B-Hib 2006 Rubella 1987 HBV 1989 DTaP-IPV-Hib-HBV PCV 2020 DTaP-IPV-Hib 2008 BCG D1 Hepatitis B (HBV) D1 Hexavalent Vaccine DTaP-IPV-HBV-Hib PCV10 (Synflorix) Measles (Sabah only) MMR (Measles Mumps, Rubella) 2 3 D1 D2 4 5 6 Years 9 12 15 D3 D1 18 21 7 13½ D1 D2 15 B D2 B D1 D1 D2 MR B DT B HPV (Girls only) Tetanus JE (Sarawak only) 13 B D1 D2 D = Dose B = Booster 112 8

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