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  1. 1. Vaccination Dr. Mitova
  2. 2. The immune system is a complex network of specialized organs and cells protects the body from destruction by foreign agents and microbial pathogens , degrades and removes damaged or dead cells, and exerts a surveillance function to prevent the development and growth of malignant cells. The immune system is composed of immune cells and central and peripheral lymphoid structures. The immune cells move throughout the body, searching for and destroying foreign substances but avoiding cells regarded as self.  
  3. 3. Natural immunity: It is not produced by the immune response. This type of immunity is present at birth and appears to be present in all members of a species.   Acquired immunity: It develops after birth as a result of exposure to an antigen, thereby activating the immune response. Acquired immunity can be either active or passive, depending on whether the immune response took place in the host or a donor.
  4. 4. Differences of immune system of children and adult The normal human no fully active immune system at birth because of immaturity. It relies instead on passively transferred antibodies from the mother. This maternal antibody slowly decreases in concentration and for all practical purposes, has waned by 1 year. The infant own production of antibody begins to be meaningful at 7 or 8 months of age when the total of maternal and infant antibody is low. One has waned and the other is not up to full strength. This is age when many of the infectious disease processes of infancy begin /e.g. otitis media, pneumonia.
  5. 5. Vaccination <ul><ul><ul><li>Vaccination </li></ul></ul></ul><ul><li>Administration of a substance to a person with the purpose of preventing a disease </li></ul><ul><li>Traditionally composed of a killed or weakened microorganism </li></ul><ul><li>Vaccination works by creating a type of immune response that enables the memory cells to later respond to a similar organism before it can cause disease </li></ul>
  6. 6. Early History of Vaccination <ul><li>Pioneered India and China in the 17th century </li></ul><ul><li>The tradition of vaccination may have originated in India in AD 1000 </li></ul><ul><li>Powdered scabs from people infected with smallpox was used to protect against the disease </li></ul><ul><li>Smallpox was responsible for 8 to 20% of all deaths in several European countries in the 18th century </li></ul><ul><li>In 1721 Lady Mary Wortley Montagu brought the knowledge of these techniques from Constantinople (now Istanbul) to England </li></ul><ul><li>Two to three percent of the smallpox vaccinees, however, died from the vaccination itself </li></ul><ul><li>Benjamin Jesty and, later, Edward Jenner could show that vaccination with the less dangerous cowpox could protect against infection with smallpox </li></ul><ul><li>The word vaccination, which is derived from vacca, the Latin word for cow. </li></ul>
  7. 7. Era of Vaccination <ul><li>English physician Edward Jenner </li></ul><ul><li>observed that milkmaids stricken with a viral disease called cowpox were rarely victims of a similar disease, smallpox </li></ul><ul><li>Jenner took a few drops of fluid from a pustule of a woman who had cowpox and injected the fluid into a healthy young boy who had never had cowpox or smallpox </li></ul><ul><li>Six weeks later, Jenner injected the boy with fluid from a smallpox pustule, but the boy remained free of the dreaded smallpox. </li></ul>
  8. 8. Era of Vacinnation <ul><li>In those days, a million people died from smallpox each year in Europe alone, most of them children. </li></ul><ul><li>Those who survived were often left with blindness, deep scars, and deformities </li></ul><ul><li>I n 1796, Jenner started on a course that would ease the suffering of people around the world for centuries to come. </li></ul><ul><li>By 1980, an updated version of Jenner vaccine lead to the total eradication of smallpox. </li></ul>
  9. 9. Early History of Vaccination <ul><li>In 1879 Louis Pasteur showed that chicken cholera weakened by growing it in the laboratory could protect against infection with more virulent strains </li></ul><ul><li>1881 he showed in a public experiment at Pouilly-Le-Fort that his anthrax vaccine was efficient in protecting sheep, a goat, and cows. </li></ul><ul><li>In 1885 Pasteur developed a vaccine against rabies based on a live attenuated virus </li></ul><ul><li>A year later Edmund Salmon and Theobald Smith developed a (heat) killed cholera vaccine. </li></ul><ul><li>Over the next 20 years killed typhoid and plague vaccines were developed </li></ul><ul><li>In 1927 the bacille Calmette-Guérin (BCG vaccine) against tuberculosis vere developed </li></ul>
  10. 10. <ul><li>Since Jenner's time, vaccines have been developed against more than 20 infectious diseases </li></ul><ul><li>  The date of introduction of first generation of vaccines for use in humans* </li></ul><ul><ul><li>1798   Smallpox </li></ul></ul><ul><ul><li>1885   Rabies </li></ul></ul><ul><ul><li>1897   Plague </li></ul></ul><ul><ul><li>1923   Diphtheria </li></ul></ul><ul><ul><li>1926   Pertussis </li></ul></ul><ul><ul><li>1927   Tuberculosis (BCG) </li></ul></ul><ul><ul><li>1927   Tetanus </li></ul></ul><ul><ul><li>1935    Yellow Fever </li></ul></ul><ul><li>After World War II </li></ul><ul><ul><li>1955   Injectable Polio Vaccine (IPV) </li></ul></ul><ul><ul><li>1962   Oral Polio Vaccine (OPV) </li></ul></ul><ul><ul><li>1964   Measles </li></ul></ul><ul><ul><li>1967   Mumps </li></ul></ul><ul><ul><li>1970   Rubella </li></ul></ul><ul><ul><li>1981   Hepatitis B </li></ul></ul>
  11. 11. Vaccination Today <ul><li>Vaccines have been made for only 34 of the more than 400 known pathogens that are harmful to man. </li></ul><ul><li>Immunization saves the lives of 3 million children each year, but that 2 million more lives could be saved if existing vaccines were applied on a full-scale worldwide </li></ul>
  12. 12. Human Vaccines against pathogens Immunological Bioinformatics, The MIT press.
  13. 16. Type of Vaccination
  14. 17. Type of Vaccination Live Vaccines <ul><li>Characteristics </li></ul><ul><ul><li>Able to replicate in the host </li></ul></ul><ul><ul><li>Attenuated (weakened) so they do not cause disease </li></ul></ul><ul><li>Advantages </li></ul><ul><ul><li>Induce a broad immune response (cellular and humoral) </li></ul></ul><ul><ul><li>Low doses of vaccine are normally sufficient </li></ul></ul><ul><ul><li>Long-lasting protection are often induced </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>May cause adverse reactions </li></ul></ul><ul><ul><li>May be transmitted from person to person </li></ul></ul>
  15. 18. Subunit Vaccines <ul><li>Relatively easy to produce (not live) </li></ul><ul><li>Classically produced by inactivating a whole virus or bacterium </li></ul><ul><ul><li>Heat </li></ul></ul><ul><ul><li>Chemicals </li></ul></ul><ul><li>The vaccine may be purified </li></ul><ul><ul><li>Selecting one or a few proteins which confer protection </li></ul></ul><ul><li>Bordetella pertussis (whooping cough) </li></ul><ul><ul><li>Create a better-tolerated vaccine that is free from whole microorganism cells </li></ul></ul>
  16. 19. Subunit Vaccines: Polysaccharides <ul><li>Polysaccharides </li></ul><ul><ul><li>Many bacteria have polysaccharides in their outer membrane </li></ul></ul><ul><ul><li>Polysaccharide based vaccines </li></ul></ul><ul><ul><ul><li>Neisseria meningitidis </li></ul></ul></ul><ul><ul><ul><li>Streptococcus pneumoniae </li></ul></ul></ul><ul><ul><li>Generate a T cell-independent response </li></ul></ul><ul><ul><ul><li>Inefficient in children younger than 2 years old </li></ul></ul></ul><ul><ul><ul><li>Overcome by conjugating the polysaccharides to peptides </li></ul></ul></ul><ul><ul><ul><ul><li>Used in vaccines against Streptococcus pneumoniae and Haemophilus influenzae. </li></ul></ul></ul></ul>
  17. 20. Subunit Vaccines: Toxoids <ul><li>Toxins </li></ul><ul><ul><li>Responsible for the pathogenesis of many bacteria </li></ul></ul><ul><li>Toxoids </li></ul><ul><ul><li>Inactivated toxins </li></ul></ul><ul><ul><li>Toxoid based vaccines </li></ul></ul><ul><ul><ul><li>Bordetella pertussis </li></ul></ul></ul><ul><ul><ul><li>Clostridium tetani </li></ul></ul></ul><ul><ul><ul><li>Corynebacterium diphtheriae </li></ul></ul></ul><ul><ul><li>Inactivation </li></ul></ul><ul><ul><ul><li>Traditionally done by chemical means </li></ul></ul></ul><ul><ul><ul><li>Altering the DNA sequences important to toxicity </li></ul></ul></ul>
  18. 21. Subunit Vaccines: Recombinant <ul><li>The hepatitis B virus (HBV) vaccine </li></ul><ul><ul><li>Originally based on the surface antigen purified from the blood of chronically infected individuals. </li></ul></ul><ul><ul><li>Due to safety concerns, the HBV vaccine became the first to be produced using recombinant DNA technology (1986) </li></ul></ul><ul><ul><li>Produced in bakers’ yeast (Saccharomyces cerevisiae) </li></ul></ul><ul><li>Virus-like particles (VLPs) </li></ul><ul><ul><li>Viral proteins that self-assemble to particles with the same size as the native virus. </li></ul></ul><ul><ul><li>VLP is the basis of a promising new vaccine against human papilloma virus (HPV) </li></ul></ul><ul><ul><ul><li>Merck </li></ul></ul></ul><ul><ul><ul><li>In phase III </li></ul></ul></ul>For more information se:
  19. 22. Genetic Vaccines <ul><li>Introduce DNA or RNA into the host </li></ul><ul><ul><li>Injected (Naked) </li></ul></ul><ul><ul><li>Coated on gold particles </li></ul></ul><ul><ul><li>Carried by viruses </li></ul></ul><ul><ul><ul><li>vaccinia, adenovirus, or alphaviruses </li></ul></ul></ul><ul><ul><li>bacteria such as </li></ul></ul><ul><ul><ul><li>Salmonella typhi, Mycobacterium tuberculosis </li></ul></ul></ul><ul><li>Advantages </li></ul><ul><ul><li>Easy to produce </li></ul></ul><ul><ul><li>Induce cellular response </li></ul></ul><ul><li>Disadvantages </li></ul><ul><ul><li>Low response in 1st generation </li></ul></ul>
  20. 23. Type of Vaccination <ul><li>Live attenuated Vaccine </li></ul><ul><ul><li>OPV </li></ul></ul><ul><ul><li>Measles </li></ul></ul><ul><ul><li>Rubella </li></ul></ul><ul><ul><li>Mumps </li></ul></ul><ul><ul><li>BCG </li></ul></ul><ul><ul><li>Varicella Vaccine </li></ul></ul><ul><li>Inactivated organism or their products </li></ul><ul><ul><li>Diphtheria </li></ul></ul><ul><ul><li>Tetanus </li></ul></ul><ul><ul><li>Pertussis( whole cell/acellular) </li></ul></ul><ul><ul><li>Hepatits Avaccine </li></ul></ul><ul><ul><li>Hepatitis B </li></ul></ul><ul><ul><li>Pneumococcal Polysaccharide vaccine </li></ul></ul><ul><ul><li>Influenza </li></ul></ul><ul><ul><li>IPV </li></ul></ul><ul><ul><li>Hib </li></ul></ul>
  21. 24. Passive Immunity <ul><li>Transfer of antibody produced by one human or other animal to another </li></ul><ul><li>Transplacental most important source in infancy </li></ul><ul><li>Temporary protection </li></ul>
  22. 25. Sources of Passive Immunity <ul><li>Almost all blood or blood products </li></ul><ul><li>Homologous pooled human antibody (immune globulin) </li></ul><ul><li>Homologous human hyperimmune globulin </li></ul><ul><li>Heterologous hyperimmune serum (antitoxin) </li></ul>
  23. 26. IMMUNOGLOBULIN PREPARETION  Normal human Ig. Normal human Ig is an antibody-rich fraction, obtained from a pool of at least 1000 donors. The preparation should contain at least 90% intact IgG; it should be as free as possible from IgG aggregates; all IgG sub-classes should be present; there should be a low IgA concentration; the level of antibody against at least two bacterial species and two viruses should be ascertained Normal human Ig used to prevent measles in highly susceptible individuals and to provide temporary protection /up to 12 weeks/ against hepatitis A infection. Live vaccines should not normally be given for 12 weeks after an injection of normal human Ig.
  24. 27.           Specific human Ig. These preparations are made from the plasma of patient who have recently recovered from an infection or are obtained from individuals who have been immunized against a specific infection. The advantages of Ig-s are: 1.      freedom from hepatitis B 2.      concentration of the antibodies into a small volume for intramuscular use. 3.      stable antibody content, if properly stored.
  25. 28. Route of Administration
  26. 29. Route of Adminstration DPT, DT Tetanus, HepatitisA, HepatitisB, Pneumococcal , Rabies, Hib, Influenza Intramuscular Measles, Mumps, Rubella, MMR, IPV, Pneumoccocal, Influenza Subcutaneous BCG, Rabies Intradermal OPV Oral
  27. 30. Site of Administration Anterolateral aspect of the thigh in infants and deltoid muscle in older children or adult. Intramuscular Anterolateral aspect of the thigh or the upper arm Subcutaneous Over the insertion of left deltoid muscle Intradermal
  28. 31. Who should not be vaccinated? <ul><li>Allergy </li></ul><ul><li>Fever </li></ul><ul><li>HIV infection </li></ul><ul><li>Immunodeficiency </li></ul><ul><li>IG administration </li></ul><ul><li>Neurological disorder </li></ul><ul><li>Prematurity </li></ul><ul><li>Reactions to Previous vaccine </li></ul><ul><li>Simultaneous administration of Vaccines </li></ul><ul><li>Thrombocytopenia </li></ul>
  29. 32. Allergy <ul><li>A. Allergic Reactions to Egg-related antigens </li></ul><ul><ul><li>Yellow fever and influenza vaccines do contain egg proteins and rarely induce immediate allergic reactions. Skin testing is recommended before administration with an history of allergic to egg </li></ul></ul><ul><ul><li>MMR- Even those with severe hypersensitivity are at low risk of anaphylaxis. </li></ul></ul>
  30. 33. Allergy <ul><li>B. Antibiotic-induced allergic reaction </li></ul><ul><ul><li>Delayed type local reaction 48-96 hours afterwards and is usually minor </li></ul></ul><ul><ul><li>IPV and OPV – streptomycin, neomycin and polymyxin B </li></ul></ul><ul><ul><li>MMR and varicella vaccine-neomycin </li></ul></ul>
  31. 34. Allergy <ul><li>C. Alum - HA </li></ul><ul><li>D. Gelatin- MMR, Varicella vaccine </li></ul>
  32. 35. Fever <ul><li>Low-grade fever or mild illness is not a contraindication for vaccination </li></ul><ul><li>Children with moderate or severe febrile illnesses can be vaccinated as soon as they are recovering and no longer acutely ill </li></ul>
  33. 36. Vaccination in Pregnancy <ul><li>Risk to a developing fetus from vaccination of the mother during pregnancy is mostly theoretical </li></ul><ul><li>Only smallpox vaccine has ever been shown to injure a fetus </li></ul><ul><li>The benefits of vaccinating usually outweigh potential risks </li></ul>
  34. 37. Vaccination in Pregnancy <ul><li>Inactivated vaccines </li></ul><ul><ul><li>Routine (influenza) </li></ul></ul><ul><ul><li>Vaccinate if indicated (hep B, Td, mening, rabies) </li></ul></ul><ul><ul><li>Vaccinate if benefit outweighs risk (all other) </li></ul></ul><ul><li>Live vaccine – do not administer </li></ul><ul><ul><li>Exception is yellow fever vaccine </li></ul></ul>
  35. 38. HIV Infection <ul><li>No BCG </li></ul><ul><li>OPV is Contraindicated </li></ul><ul><ul><li>in household contact, in recipient ( asymptomatic or symptomatic) </li></ul></ul><ul><ul><li>IPV for these children and household contacts </li></ul></ul><ul><li>MMR vaccination should be considered for all asymptomatic and to all symptomatic HIV-infected persons who do not have evidence of severe immunosuprresion or measles immunity </li></ul><ul><li>Pneumococcal vaccine, Hib, DTP (or DTaP), Hepatitis B vaccine, Influenza vaccines are all indicated </li></ul>
  36. 39. Immunosupression <ul><li>No live viral vaccines and BCG. IPV for these patients, their siblings and their household contacts </li></ul><ul><li>No live vaccine (except varicella) until six months after immunosuppressive therapy </li></ul>
  37. 40. Neurological disorder <ul><li>Progressive developmental delay or changing neurological findings (e.g. infantile spasm) - defer pertussis immunization </li></ul><ul><li>Personal history of convulsions Recent seizures - defer pertussis immunization </li></ul><ul><li>Conditions predisposing to seizures or neurological deterioration (e.g. tuberous sclerosis) - defer pertussis immunization </li></ul>
  38. 41. Reactions <ul><li>Severe Reactions to DTP </li></ul><ul><ul><li>Insonable cry lasting more than 3 hrs with 48 hrs of dose </li></ul></ul><ul><ul><li>Seizure with 3 days </li></ul></ul><ul><ul><li>Severe local reactions </li></ul></ul><ul><ul><li>Family hx of adverse event </li></ul></ul><ul><li>Not a contraindication, but consider carefully the benefits and risks, if need to vaccinate can use acellular DTP for less reactions </li></ul>
  39. 42. Reactions <ul><li>GBS with 6 weeks after a dose of DTP </li></ul><ul><ul><li>Again based on risks and benefits for further dose of DTP and risk of GBS recurrence. </li></ul></ul>
  40. 43. Reactions <ul><li>Contraindication for further dose of DTP </li></ul><ul><ul><li>encephalopathy within 7 days of a dose of DTP </li></ul></ul>
  41. 44. VACCINE REACTIONS <ul><li>Common, minor reactions </li></ul><ul><ul><li>vaccine stimulates immune system </li></ul></ul><ul><ul><li>settle on their own </li></ul></ul><ul><ul><li>warn parents and advise how to manage </li></ul></ul><ul><li>Rare, more serious reactions </li></ul><ul><ul><li>anaphylaxis (serious allergic reaction) </li></ul></ul><ul><ul><li>vaccine specific reactions </li></ul></ul>
  42. 45. RARE, MORE SERIOUS REACTIONS BCG Hib HepB Measles/ MMR/MR <ul><li>Suppurative lymphadenitis </li></ul><ul><li>BCG osteitis </li></ul><ul><li>Disseminated BCG infection </li></ul><ul><li>1 in 1000 to 1 in 10 000 </li></ul><ul><li>1 in 3000 to 1 in 100 million </li></ul><ul><li>~1 in 1 million </li></ul><ul><li>None known </li></ul><ul><li>Anaphylaxis </li></ul><ul><li>1 in 6-900 000 </li></ul><ul><li>Febrile seizures </li></ul><ul><li>Thrombocytopaenia </li></ul><ul><li>(low platelets) </li></ul><ul><li>Severe allergic reaction </li></ul><ul><li>Anaphylaxis </li></ul><ul><li>Encephalopathy </li></ul><ul><li>1 in 3000 </li></ul><ul><li>1 in 30 000 </li></ul><ul><li>~1 in 100 000 </li></ul><ul><li>~1 in 1 million </li></ul><ul><li><1 in 1 million </li></ul>Reaction Incidence
  43. 46. RARE, MORE SERIOUS REACTIONS (2) Tetanus Pertussis ( DTP- whole cell) Reaction Incidence Polio (OPV) <ul><li>Vaccine associated paralytic poliomyelitis </li></ul><ul><li>Risk is higher for first dose, adults, and immunocompromised </li></ul><ul><ul><li>1 in 2.4-3.3 million doses </li></ul></ul><ul><ul><li>1 in 750 000 first dose compared to 1 in 5.1 million for subsequent doses </li></ul></ul><ul><ul><li>Brachial neuritis </li></ul></ul><ul><ul><li>Anaphylaxis </li></ul></ul><ul><ul><li>0.5-1 in 100 000 </li></ul></ul><ul><ul><li>1 in 100 000 to 1 in 2 500 000 </li></ul></ul><ul><ul><li>Persistent inconsolable screaming </li></ul></ul><ul><ul><li>Seizures </li></ul></ul><ul><ul><li>Hypotonic, hyporesponsive episode (HHE) </li></ul></ul><ul><ul><li>Anaphylaxis </li></ul></ul><ul><ul><li>Encephalopathy (Note: Risk may be zero) </li></ul></ul><ul><ul><li>1 in 15 to 1 in 1000 </li></ul></ul><ul><ul><li>1 in 1750 to 1 in 12 500 </li></ul></ul><ul><ul><li>1 in 1000 to 1 in 33 000 </li></ul></ul><ul><ul><li>1-6 in million </li></ul></ul><ul><ul><li>0-1 in 1 million </li></ul></ul>
  44. 47. Simutaneous administration of Vaccine <ul><li>A theoretical risk that administration of multiple live virus vaccine: OPV, MMR, and varicella ) within 28 days of one another if not given on the same day will result in a sub optimal immune response </li></ul><ul><li>No data to substantiate this </li></ul>
  45. 48. V accine C old C hain <ul><li>Maintaining proper vaccine temperatures during storage and handling to preserve potency </li></ul><ul><li>The success of efforts against vaccine-preventable diseases is attributable in part to proper storage and handling of vaccines. </li></ul><ul><li>Exposure of vaccines to temperatures outside the recommended ranges can affect potency adversely, thereby reducing protection from vaccine-preventable diseases </li></ul>
  46. 49. Recommended Storage Temperatures
  47. 50. Recommended Schedule for Immunization of Healthy Infants and Children/BULGARIA/   24 h HB vax 0.5 ml i.m. 48h BCG 0.1 ml i.d. 1mo HB vax 0.5ml i.m. 2mo Pentaxim(DTaP, I PV,Hemophilus infl B).0.5ml i.m. ;vaccineS.pneumoniae-0,5i.m. 3mo Pentaxim(DTaP, IPV,Hemophilus infl B).0.5ml i.m. vaccineS.pneumoniae-0,5i.m 4mo Pentaxim(DTaP, IPV,Hemophilus infl B).0.5ml i.m. vaccineS.pneumoniae-0,5i.m 6mo HB vax 1 2 mo vaccine against S.pneumoniae-0,5i.m. (booster) 13mo MMR 0.5ml i.m. 16-24mo Pentaxim(DTaP, IPV,Hemophilus infl B).0.5ml 6у Tetraxim( IPV , DTaP)-0.5ml i.m. 7y Mantoux 0.1i.d .(negative<5mm-BCG) 1 1 y Mantoux .(negative<5mm-BCG) 12y MMR , Td 17y Td,Mantoux .(negative<5mm-BCG) 25,35,45…y Td 0.5ml i.m.