Faculty of Medicine Applied Vaccination By Hatim Jaber MD MPH JBCM PhD 12 -12- 2017

Presentation outline Introduction to Immunology 14:00– 14:10 Time Introduction to Immunology 14:00– 14:10 Vaccine-preventable diseases Classification of Vaccines 14:10– 14:20 Principles of Vaccination Routes of administration 14:20– 14:30 General Recommendations = Precautions and Contraindications 14:30– 14:50

World Immunization Week 24-30 April Immunization averts 2 to 3 million deaths annually; however, an additional 1.5 million deaths could be avoided if global vaccination coverage improves. Today, an estimated 18.7 million infants – nearly 1 in 5 children – worldwide are still missing routine immunizations for preventable diseases, such as diphtheria, pertussis and tetanus.

World Immunization Week, 24-30 April 2017

Global Vaccine Action Plan Goals of the Decade of Vaccines (2011–2020)

Defense Mechanisms External defense Internal Defense Immune Defense

What is immunity? Immunity is the body's ability to fight off harmful micro-organisms –PATHOGENS- that invade it. The immune system produces antibodies or cells that can deactivate pathogens.

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”.

What’s the difference between Vaccination and Immunization Immunization is the process of protecting people against harmful infections before they come into contact with them. It does this by using the body’s own natural defense system, the immune response. Vaccination just means having the injection. When you are vaccinated, your body produces an immune response, just as you would if you were exposed to the infection, but without having the symptoms, and this builds up your resistance to that infection.

Vaccine-preventable diseases Vaccine-preventable diseases include: Cervical cancer Cholera Diphtheria Hep B Influenza Japanese encephalitis Measles Mumps Pertussis Vaccine-preventable diseases include: Pneumonia Polio Rabies Rotavirus Rubella Tetanus Typhoid Varicella Yellow Fever

Hib=(Haemophilus influenzae type b)

Vaccine Preventable Diseases (VPDs) World immunization coverage up from 10% in 1970s to 80% in 1990s, 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 Coverage is good; Adapt and expand

NON-Vaccine Preventable Diseases????????

Eradication or Control of VPDs 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, may achieve local elimination Local elimination is where domestic circulation of a virus is interrupted with cases occurring from importation only

Herd Immunity Herd immunity can be defined as the resistance of a population to the introduction and spread of an infectious agent, based on the immunity of a high proportion of individual members of the population, thereby lessening the likelihood of a person with a disease coming into contact with b susceptible. Example - If 90 % of the children are vaccinated for measles, the remaining 10 % of the children who are not vaccinated might not become infected with measles because most of the children (90 %) are vaccinated. That means transmission from infected person to other susceptible children will not be easier. Can lead to disappearance of diseases (smallpox) Vaccination no longer necessary

Types of Acquired Immunity

Immunoglobulin and antiserum Human normal immunoglobulin Human specific immunoglobulin Non human Ig (antisera, antitoxins) Hepatitis A Measles Rabies Tetanus Mumps Hepatitis B Varicella Diphtheria Gas gangrene Botulism

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

Types of vaccines Live vaccines Attenuated vaccines Killed Inactivated vaccines Toxoids Cellular 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 Rabies Salk polio Intra-muscular influenza Japanise encephalitis Diphtheria Tetanus Meningococcal polysaccharide vaccine Pneumococcal polysaccharide vaccine Hepatitis B polypeptide vaccine Hepatitis B vaccine

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)

Vaccine administration Intranasal route (live attenuated influenza vaccine)

Injection site Intramuscular Injections Site Preterms & neonates Anterolateral thigh (junction of middle & lower third) Infants Toddlers & older children Deltoid or Anterolateral thigh Adolescents & adults Deltoid Subcutaneous Injections thigh >12 months Outer triceps Intradermal Injections All age Left deltoid

Vaccination schedule preschool -Jordan Vaccine Age BCG 1st contact DaPT1+HepB1+Hib1+IPV1 2 months DaPT2+HepB2+Hib2+IPV2+OPV 3 months DaPT3+HepB3+Hib3+OPV 4 months Measles + OPV 9 months MMR1 12 months DPTbooster1 +OPV booster1 +MMR2 18 months

IAP recommendations for immunization in adolescents Vaccines Schedule MMR 2 doses at 4-8 weeks interval Hepatitis B 3 doses at 0,1 & 6 months Hepatitis A 2 doses at 0 & 6 months Typhoid 1 dose every 3 years Varicella Influenza 1 dose every year JE vaccine Catch-up up to 15 years Tdap 1 dose followed by Td booster every 10 years

Vaccination for travelers the most frequent vaccine-preventable diseases and the dose schedules

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).

Changes in immunoglobulin levels with age

Why multiple doses necessary? Single does may not provide sufficient immunity (e.g. HIB) Immunity wanes over time; “booster” dose is needed (DTaP) Single dose does not produce immunity for everyone (e.g. measles) Vaccine components change over time (e.g. influenza)

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.

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%) cholera vaccine, and influenza killed vaccine.

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.

Principles of vaccination

Principles of Vaccination The primary goal in vaccination is to provide protective immunity by inducing a memory response to an infectious microorganism using a non-toxic antigen preparation. It is important to produce immunity of the appropriate kind: antibody / or cellular immunity. Antibodies produced as a result of immunization are effective primarily against extracellular organisms and their products e.g., toxins. Passively administered antibodies have the same effect as induced antibodies. Cell-mediated immunity (T cells, macrophages) induced by vaccination is important particularly in preventing intracellular bacterial and viral infections and fungal infections.

Principles of Vaccination 4.The ultimate goal of any immunization program is the eradication of the disease. 5.This requires that the infection is limited only to humans, with no animal or environmental reservoir, and the absence of any subclinical or carrier state in humans. 6.Achieving elimination requires a high level of herd immunity to prevent person to person spread. 7.This requires considerable infrastructure support to ensure that all at-risk populations are targeted for immunization. 8.This has been achieved for small pox, although we are close to the elimination of polio.

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

Adverse events after vaccination are grouped into five categories, depending on whether they are due to: • the vaccine product: an adverse event caused or precipitated by a vaccine due to one or more of its inherent properties. Example: extensive limb swelling after administration of DTP vaccine • quality: an adverse event caused or precipitated by a vaccine with one or more defects, including the administration device provided by the manufacturer. Example: paralytic poliomyelitis due to failure by a manufacturer to completely inactivate a lot of poliovirus vaccine • vaccination error: an adverse event due to inappropriate handling, prescription or administration of a vaccine. Example: transmission of infection from a contaminated multidose vial • anxiety: an adverse events arising from anxiety about the procedure. Example: vasovagal syncope in an adolescent during or after vaccination • a coincidental event: an adverse event caused by an event other than the vaccine, vaccination error or anxiety. Example: a fever occurring at the time of vaccination (temporal association) that is in fact due to a viral infection

Main minor and severe reactions associated with vaccination

Different type of adverse events following immunization Vaccine reaction Event caused/precipitated by the inherent properties of the vaccine (active component, adjuvant, preservative, stabilizer) when given correctly Program errors Event caused by an error in vaccine preparation, handling or administration Coincidental Event that happens after immunization but is not caused by the vaccine Injection reaction Event arising from anxiety about, or pain from, the injection itself rather than the vaccine Unknown The cause of the event cannot be determined

Common minor vaccine reactions Local reaction (pain, redness, swelling) Fever Irritability, malaise & non specific reactions BCG common Hib 5-15% 2-10% Hep-B Adults-15% Children-5% 1-6% Measles/MMR 10% 50% (rash) OPV <1% TT/DT/Td 25% DPwT 50% 60%

Rare serious vaccine reactions BCG Suppurative adenitis, BCG osteitis, Disseminated BCGitis Hep-B Anaphylaxis Measles/MMR Febrile seizures, thrombocytopenia, anaphylaxis OPV VAPP TT Brachial neuritis, anaphylaxis, sterile abscess DTP Persistent inconsolable screaming, seizures, HHE, anaphylaxis, shock JE Serious allergic reactions, neurological events YF Allergic reactions/anaphylaxis

Differential diagnosis of fainting and anaphylaxis

Reactions due to anxiety about vaccination Fainting is relatively common, mainly among older children and adults. This vasovagal reaction may lead to loss of postural tone and consciousness • Hyperventilation due to anxiety about vaccination can cause light-headedness, dizziness and tingling around the mouth and in the hands. • Vomiting: Vomiting is a common anxiety symptom in young children. Breath-holding spells may occur, which can result in brief unconsciousness, during which breathing resumes. • Convulsions: An anxiety reaction to injection can, on rare cases, include convulsions. Convulsions usually occur in the context of a vasovagal reaction and syncope, soon after or with the loss of postural tone and consciousness that characterizes syncope. Such seizures are due to anoxia, are usually self-limited and benign and do not require antiepileptic drug therapy.

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. No. persons immunized in specified age group = ------------------------------------------------------------ X 100 No. persons in the age group during that year

WHO UNICEF estimates time series for Jordan

Vaccines Contraindications and Precautions

Active untreated tuberculosis. Who should NOT receive a vaccine? Contraindications to any routine active immunization procedure Severe allergy to any vaccine component Severe reaction to same vaccine in past Individuals with certain immunodeficiencies (live vaccines) An acute febrile illness, malaise, cough, diarrhea, or other symptoms requiring medical treatment. Children who have had convulsions, fits, cerebral damage or irritation in the neonatal period or any neurological disorder which appears to be active should not normally have DTP vaccine as a routine. They should be referred for specialist advice. Active untreated tuberculosis.

Contraindications to the use of live attenuated vaccines Immunocomproised infants and children. Patients suffering from any malignant condition such as leukemia or Hodgkin’s disease. Patients undergoing treatment with corticosteroid (other than topical steroids), alkalating agents, antimetabolites or those receiving radiotherapy. Organ transplantations. Pregnancy, Sever protein energy malnutrition or kwashiorkor???????

There are very few contraindications to rotavirus vaccines. a history of a severe allergic reaction (e.g. anaphylaxis) after a previous dose of either rotavirus vaccine or any component of the vaccine being given; • severe combined immunodeficiency; the risk–benefit ratio for children with known or suspected altered immunocompetence should be assessed individually. Children and adults with congenital immunodeficiency, haematopoietic transplantation or solid organ transplantation sometimes experience severe or prolonged rotavirus gastroenteritis. • a history of intussusception, which places children at greater risk than children who have never had it.

These are not contraindications to Routine Immunization · Minor illnesses such as upper respiratory infections or diarrhoea, mild fever (< 38.5°C) · Allergy, asthma · Prematurity, underweight newborn child · Malnutrition??????????????????????? Under nutrition, failure to thrive . · Child being breastfed · Family history of convulsions · Treatment with antibiotics · Dermatoses, eczema or localized skin infection · Chronic diseases of the heart, lung, kidney and liver · Stable neurological conditions, such as cerebral palsy and Down's syndrome · History of jaundice after birth

Conditions which are NOT Contraindications (cont.) - An antibiotic course just completed. -Congenital heart disease, chronic diseases of the chest, eg. Cystic fibrosis (these are important indications for immunization) - Prematurely, or preterm delivery. - Nappy rash. - Breast feeding. - Topical steroids.

Invalid Contraindications Minor Illness Low grade fever Upper respiratory infection Otitis media Mild diarrhea Only one small study has suggested decreased efficacy of measles vaccine in children with URI Findings not replicated by multiple prior and subsequent studies No evidence of increased adverse reactions

Summary Current recommended vaccinations are safe and effective No vaccines are 100% effective or 100% risk-free Current recommendations based on best available scientific data Schedule reviewed/updated annually

Summary and Conclusion Vaccination is cornerstone of PH Children and other groups Rapidly developing field First priority in public health after safe water and food National programs must be revised annually