VACCINATION AND IMMUNIZATION Public Health III MUDr. Bohdana Rezková, Ph.D. IMMUNIZATION POSSIBILITIES OF IMMUNIZATION IMMUNIZATION NATURALLY ACQUIRED ARTIFICIALLY ACQUIRED ACTIVE AFTER INFECTION AFTER VACCINATION PASSIVE TRANSPLACENTAL TRANSFER OF IG IG PREPARATIONS TRANSFER PASSIVE IMMUNIZATION I. • reception of pre-formed specific antibodies from an exogenous source homologous (human) x heterologous (animal) antibodies, monoclonal antibodies produced by biotechnology • polyclonal Ig, hyper Ig, antitoxins • temporary protection: 4 - 6 weeks • risk of strong side effects at heterologous Ig (allergy, anaphylaxis, serum sickness): fractionated administration during hospitalization with continual observation only at very dangerous and necessary cases • can inactivate live attenuated viral vaccines like varicella, measles, OPV, and rotavirus vaccines. PASSIVE IMMUNIZATION II. Indications and preparations 1. Prophylaxis of dangerous infections or in individuals at risk 2. Therapy of severe acute infections and intoxications (tetanus, diphteria,…) 3. Protection for individuals who cannot be vaccinated because they are immunodeficient or immunocompromised (intraveneous polyclonal Ig - IVIG). Tetanus immunisation and prophylaxis following injuries https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/820628/Tetanus_informat ion_for_health_professionals_2019.pdf ACTIVE IMMUNIZATION • one of the most beneficial and cost-effective disease prevention measures • one of the most important inventions in medicine, • method that used natural ways of bodies protection, • key process – arising of immunological memory faster and more powerful immunity response, You do not need to have your children vaccinated. When the epidemic comes, we'll burn the witch. Finally Jane found a real expert…. „Vaccination - the pros and cons“ (vitalia.cz): • Question: Do you think it is normal to give a small child a vaccine in which there are seven diseases at once? Even with poisonous additives! • Answer: It's not normal. It's a crime against humanity! MUDr. Ludmila Elekova • Is it possible for a vaccinated child to get the disease against which it is vaccinated? • Is it true that vaccination reduces immunity to other diseases? • Can vaccines cause autism? • Wouldn't it be better to postpone some vaccinations until later? Little child can hardly catch jaundice B…. • Isn't it dangerous to vaccinate so many infections at once? • Why is aluminum used in vaccines? Isn't it dangerous for the baby? HOW? AGAINST WHAT? WHAT THEN? WHO? WHY? BY WHAT? WHOM? WHEN NOT? WHEN? OVERVIEW I. INTRODUCTION TO VACCINOLOGY • Importance of vaccination • Composition of vaccine • Classification of vaccines • Immune response to vaccines • Vaccination contraindications • Side effects of immunization • Principles of right vaccination • Vaccination programs II. SPECIAL VACCINOLOGY • Vaccinations preventable diseases • Vaccinations for travellers IMPORTANCE OF VACCINATION I. INTRODUCTION TO VACCINOLOGY 1796 - Edward Jenner showed efficacy of smallpox vaccine 1801 – vaccination commenced in the UK 1802 - vaccination started in the Czech lands 1959 – WHO accepted plan for eradication MAIN STRATEGY: • mass vaccination strategies: mass vaccination of the population with a target of 80% vaccine coverage in each country, • surveillance and anti-epidemic strategies: reporting of variegated disease, regular screening actions, strict isolation of patients, rapid vaccination of all persons in contact with the sick person to interrupt the spread of the disease where vaccination is low. Mass campaign Declaration of eradication and vaccination ONLY ONE NOT VACCINATED HERD IMMUNITY - percentage of immune people in the population needed to prevent the spread of the agent. IMPACTS OF VACCINATION DIRECT EFFECT • resulted from immune response of organisms to vaccine creation of individual immunity INDIRECT EFFECT • impact on disease transmission in the population creation of herd immunity • prevents the disease or its severe course • stops the spread of infections in the population • helps protect unvaccinated persons Clinical Infectious Diseases, Volume 52, Issue 7, 1 April 2011, Pages 911–916, https://doi.org/10.1093/cid/cir007 The content of this slide may be subject to copyright: please see the slide notes for details. Simple threshold concept of herd immunity What defines the protective thresholds of herd immunity and public health strategies? • infectivity of the agent • immunogenicity of the vaccine and type of immune response • duration of infectiousness in the infected persons • duration of vaccination induced immunity • homogeneity of population (interaction between age group,…) Clinical Infectious Diseases, Volume 52, Issue 7, 1 April 2011, Pages 911–916, https://doi.org/10.1093/cid/cir007 The content of this slide may be subject to copyright: please see the slide notes for details. Diagram illustrating transmission of an infection with a basic reproduction number R0 = 4 NOT VACCINATED PROTECTED https://youtu.be/V9DinPkjbgo IMPORTANCE OF VACCINATION COMPOSITION OF VACCINES I. INTRODUCTION TO VACCINOLOGY VACCINE INGREDIENTS ANTIGEN STABILIZERS RESIDUAL SUBSTANCES PRESERVATIVES ADJUVANTS ADJUVANTS • added to some vaccines to enhance the immune response, • benefit for people with compromised immune systems, the elderly, and the very young, use of less antigen (in short supply or costly), reducing or eliminating the need for booster vaccinations • Aluminum-containing adjuvants • others: AS04, MF59, AS01B, … RESIDUAL SUBSTANCES - ANTIBIOTICS • in some vaccines, • used to help prevent bacterial contamination during manufacturing small amounts of antibiotics may be present in some vaccines, • e.g. neomycin, polymyxin B, streptomycin, gentamicin, • antibiotics most likely to cause severe allergic reactions (e.g., penicillins, cephalosporins and sulfa drugs) are not used in vaccine production! STABILIZERS • help protect the vaccine from adverse conditions (e.g. temperature). • various substances - e.g.: ➢sugars such as sucrose and lactose, ➢amino acids such as glycine or the monosodium salt of glutamic acid ➢proteins such as human serum albumin or gelatin. ANTIGEN • any substance inducing a desired immune response in a vaccinated person, • complex (live vaccines) or with one (HepB) or more components (acellular pertussis vaccine), • alone (≥ 5 kdal) or conjugated with some proteins (e.g. with a toxoid) CONJUGATED VACCINES PRESERVATIVES • to prevent the growth of bacteria or fungi that may be introduced into the vaccine during its use (e.g. repeated puncture of a multi-dose vaccine vial with a needle). • THIMEROSAL IMPORTANCE OF VACCINATION CLASSIFICATION OF VACCINES I. INTRODUCTION TO VACCINOLOGY TYPES OF VACCINES 1. Live-attenuated vaccines 2. Inactivated vaccines 3. Subunit, recombinant, polysaccharide, and conjugated vaccines 4. Toxoid vaccines • Whole-Pathogen Vaccines • Subunit Vaccines • Nucleic Acid Vaccines WHOLE – PATHOGEN VACCINES LIVE-ATTENUATED VACCINES • contain a version of the living microbe that has been weakened in the laboratory • vaccine against measles, mumps and rubella (MMR), varicella, TB, oral polio, … • elicit strong immune responses • life-long immunity after only one or two doses • stronger and more frequent side effects INACTIVATED VACCINES • produced by killing the pathogen with chemicals, heat or radiation • vaccine against rabies, hepatitis A, TBE, polio - Salk, typhoid fever,… • side effects are weaker • immune response is not so strong (need of 3 doses) SUBUNIT VACCINES I POLYSACCHARID VACCINES • based on the polysaccharides, or sugars, that form the outer coating of bacteria • activate only T – indep. immunity • short – term immunity • age limited indications • CONJUGATED VACCINES • polysaccharide is conjugated to a protein antigen to offer improved protection (e.g. toxoid) • change immune response – useful for young children and elderly people • against Hib, pneumococcal and meningococcal infections. - include only the components, or antigens, that best stimulate the immune system, - antigens alone are not sufficient to induce adequate long-term immunity + adjuvants, - are safer and easier to produce. SUBUNIT VACCINES II TOXOID VACCINES • chemically inactivated toxins (toxoids), • elicit immune responses against disease-causing proteins, or toxins, secreted by the bacteria, • against bacterial illnesses, such as diphtheria and tetanus. RECOMBINANT VACCINES • recombinant DNA technology, • genetic code for the viral protein has been inserted into other cells which then produce it, • against hepatitis B, Men B, HPV NUCLEIC ACID VACCINES • use introduction of genetic materials encoding one or more antigens of pathogen into the body cells, they then produce the antigen stimulation of broad long-term immune responses, • relative ease of large-scale vaccine manufacture, • excellent vaccine stability, • in the research pipeline, not currently licensed for human use, • e.g. DNA plasmid vaccines KINDS OF VACCINES 1. SIMPLE X COMBINED – against one or more infections (e.g. MMR, hexavaccine,…) 2. MONOVALENT X POLY (…) VALENT – against one or more serotypes of one pathogen (e.g. tetravalent vaccine against meningococcus A,C,W,Y) IMPORTANCE OF VACCINATION IMMUNE RESPONSE TO VACCINATION I. INTRODUCTION TO VACCINOLOGY 3 ways of interaction between vaccine antigens and immune system Source: J. Beran :Physiology of immune response to vaccination. Available at: https://www.vakcinace.eu/pred nasky-stud . COMPARISON OF IMMUNE RESPONSE POLYSACCHARID VACCINES Ig M, no immunologic memory CONJUGATED VACCINES: Ig G, immunologic memory IMPORTANCE OF VACCINATION SIDE EFFECTS OF VACCINATION IMMUNE RESPONSE TO VACCINATION I. INTRODUCTION TO VACCINOLOGY SIDE EFFECTS OF VACCINES • Any vaccine can cause side effects. • All side effects are monitored by national institution systems. • Expected x unexpected • Local x general • From the view of severity: 1. Physiological side effects 2. Severe side effects (physiological or neurological) 3. Allergic side effects CAUSALITY ASSESSMENT FOR POTENTIAL ADVERSE EVENTS 1. Evidence convincingly supports a causal relationship (e.g. the oral polio vaccine and vaccine-associated paralytic polio) 2. Evidence favors acceptance of a causal relationship 3. Evidence is inadequate to accept or reject a causal relationship 4. Evidence favors rejection of a causal relationship https://www.nap.edu/catalog/13164/adverse-effects-of-vaccines-evidence- and-causality COMMON PHYSIOLOCIGAL SIDE EFFECTS • Local reaction (redness and/or swelling around injection site) • Mild temperature or fever • Irritability, decreased appetite, sleepiness • Vomiting and diarrhoea • Fainting (uncommon; however, this may sometimes occur) sometimes happen 1 to 3 days after the vaccination SEVERE SIDE EFFECTS Each side effect that causes: • Death • Life threat • Severe alteration of organisms • Long term damage • Hospitalisation • Congenital anomaly in descendants NEUROLOGICAL SIDE EFFECTS • febrile seizures • Guillain-Barré Syndrome • encephalitis • encephalomyelitis • non-stop crying for 3 hours or more ANAPHYLACTIC REACTION • usually occur within minutes of parenteral administration, • most common signs and symptoms are cutaneous (e.g. urticaria, angioedema, flushing, pruritus). However, 10 to 20% of patients have no skin findings. • rapid progression of symptoms, evidence of respiratory distress (e.g., stridor, wheezing, dyspnoea, increased work of breathing, retractions, persistent cough, cyanosis), signs of poor perfusion, abdominal pain, vomiting, dysrhythmia, hypotension, collapse, • first and most important therapy - epinephrine, • providers should have a plan in place to contact emergency medical services. IMPORTANCE OF VACCINATION CONTRAINDICATIONS OF VACCINATION SIDE EFFECTS OF VACCINATION IMMUNE RESPONSE TO VACCINATION I. INTRODUCTION TO VACCINOLOGY GENERAL CONTRAINDICATIONS • Conditions in a recipient that increases the risk for a serious adverse reaction. • Persons who administer vaccines should screen patients for contraindications! 1. Severe allergic reaction (e.g. anaphylaxis) after a previous dose or to a vaccine component. 2. Severe reaction after previous dose with alteration of general condition. CONRAINDICATIONS FOR LIVE VACCINES • Pregnant women • General contraindications • Diagnosed immunodeficiency • Treatment by Corticosteroids (0,5 mg/kg/2 weeks) • Specific biological treatment • Selected haemato-oncological or haematological diagnosis • 3 months after transfusion or passive immunization PRECAUTIONS • Condition in a recipient that might increase the risk of a serious adverse reaction. • In general, vaccinations should be deferred when a precaution is present. • Vaccination might be indicated in the presence of a precaution if the benefit of protection from the vaccine outweighs the risk for an adverse reaction. 1. Moderate or severe acute illness with or without fever. 2. Other specific precautions at various vaccines. IMPORTANCE OF VACCINATION PRINCIPLES OF RIGHT IMMUNISATION SIDE EFFECTS OF VACCINATION IMMUNE RESPONSE TO VACCINATION I. INTRODUCTION TO VACCINOLOGY CONTRAINDICATIONS OF VACCINATION PROPER VACCINE ADMINISTRATION • critical to ensure that vaccination is safe and effective. • Vaccine administration protocol (CDC): 1. Review vaccination history 2. Assess for Needed Immunizations 3. Screen for Contraindications and Precautions 4. Educate the Parent or Patient 5. Prepare the Vaccine(s) 6. Administer the Vaccine (use conventional or abbreviated scheme) 7. Document the Vaccination(s) VACCINATION SCHEME • basic (conventional) scheme) - number of doses needed for adequate and prolonged protection, varies from vaccine to vaccine, x abbreviated scheme • booster dose - for some vaccines, later in life to maintain protection. BEST PRACTICES FOR MULTIPLE INJECTIONS • Label each syringe to identify the vaccine it contains. • Separate injection sites by 1 inch or more, if possible. • Administer vaccines that may be more likely to cause a local reaction (e.g., tetanus-toxoid-containing and PCV13) in different limbs, if possible. • Use combination vaccines (e.g., DTaP-IPV-HepB or DTaP-IPV/Hib), if appropriate, to decrease the number of injections. https://www.cdc.gov/vaccines/hcp/admin/administer-vaccines.html CDC RECOMMENDED INTERVALS BETWEEN ADMINISTRATIONS OF DIFFERENT TYPES OF VACCINES (IF NOT ON SAME DAY) COMBINATIONS OF ANTIGENS RECOMMENDED MINIMUM INTERVAL ≥ 2 INACTIVATED NO INTERVAL, COULD BE AMINISTERED ANYTIME INACTIVATED AND LIVE NO INTERVAL, COULD BE ADMINISTERED ANYTIME ≥ 2 LIVE - ADMINISTRED PARENTERALLY 4 WEEKS, IF NOT ADMINISTERED ON SAME DAY AFTER BCG PRIMOVACCINATION 8 WEEKS OR AFTER THE LESION HEALED IMPORTANCE OF VACCINATION SIDE EFFECTS OF VACCINATION IMMUNIZATION PROGRAMS IMMUNE RESPONSE TO VACCINATION I. INTRODUCTION TO VACCINOLOGY CONTRAINDICATIONS OF VACCINATION IMMUNIZATION PROGRAMS • All countries have a national immunization programme to protect the population against vaccine-preventable diseases. • WHO: the Expanded Programme on Immunization (EPI) https://vaccine-schedule.ecdc.europa.eu/ VACCINATION PREVETABLE DISEASES RUTINE VACCINATION • BCG • Measles • Rubella • Mumps • Pertusiss • Tetanus • Diphteria • Influenza • TBE • Meningococcal diseases • Pneumococcal diseases • Rotavirus • Poliomyelitis • Hepatitis A • Hepatitis B • HiB • Varicella – Zoster • HPV MEASLES https://www.youtube.com/watch?v=zBkVCpbNnkU MEASLES I. • Acute, highly contagious viral disease (infectivity is close to 100% in susceptible individuals). • CA: RNA virus of the genus Morbillivirus and the family Paramyxoviridae. • Transmitted mainly directly via respiratory droplets but also by air as indirect way of transmission (several hours later). • Infectiousness - from about five days before the onset of rash to four days afterwards. • Maximally contagious during the prodromal phase - lasts for 2–4 days (intense coughing!). MEASLLES II. • Incubation period - 10–12-day. • Prodromal phase - fever, conjunctivitis, coryza, cough and bronchiolitis. • Koplik’s spots, the enanthema believed to be pathognomic for measles, appear on the buccal mucosa 1–2 days before the onset of rash. • The measles rash, an erythematous maculopapular exanthema, develops 2–4 days after the onset of fever and spreads from the head to the body over the next 3–4 days. MEASLES III. • The most common complications: ➢otitis media (7–9%), ➢pneumonia (1–6%), ➢diarrhoea (8%), ➢post-infectious encephalitis (1 per 1000 to 2000 cases), ➢subacute sclerosing panencephalitis (SSPE), which affects 1 per 100 000 cases. • Case fatality is 1–3 per 1000 cases (predominantly caused by complicating bacterial infections). MEASLES IN EUROPE MEASLES – EPIDEMIOLOGICAL RISK • Vaccination coverage is below 95% in most countries! • Measles cases in Europe primarily occur in unvaccinated populations in both adults and children. • Large outbreaks with fatalities are ongoing in countries that had previously eliminated or interrupted endemic transmission! MEASLES – VACCINATION • MMR - a combination measles, mumps, and rubella vaccine. • MMRV (ProQuad ) - a combination measles, mumps, rubella, and varicella vaccine. • Both vaccines contain live, attenuated viruses. • CDC recommends two doses of measles-containing vaccine routinely for children. • The first dose at age 12 through 15 months and the second dose at age 4 through 6 years before school entry. VACCINATION FOR TRAVELLERS • international travel can pose various risks to health, • consultation - at least 4–8 weeks before the journey – at the travel medicine clinic or medical practitioner. VACCINES FOR TRAVELLERS (WHO) SELECTIVE USE FOR TRAVELLERS • Cholera • Hepatitis A • Hepatitis E • Japanese encephalitis • Meningococcal disease • Rabies • Tick-borne encephalitis • Typhoid fever • Yellow fever REQUIRED VACCINATION • Yellow fever (Country list) • Meningococcal disease and polio (required by Saudi Arabia for pilgrims, updates are available on www.who.int/wer) YELLOW FEVER • mosquito-borne infection of primates, • caused by a virus of the Flavivirus genus, • transmitted between monkeys by forest-dwelling primatophilic Aedes mosquitoes Sylvatic infection of humans (hunt, gather food) + Aedes aegypti in towns and villages human to human transmission). • in west, central and east Africa and in South America, from Panama to the northern part of Argentina, never in Asia, once endemic in Europe. • a wide spectrum of symptoms, from mild to fatal. • live attenuated vaccine, known as YF 17D – effective and safe. CHOLERA • acute diarrhoeal infection, • caused by the bacterium Vibrio cholera of serogroups O1 or O139. • humans are the only relevant reservoir, even though Vibrios can survive for a long time in coastal waters contaminated by human excreta, • several countries in Africa, Asia and the Americas are reporting cholera outbreaks, • major outbreaks: Yemen, Nigeria, the DRC, Haiti, • oral inactivated vaccine. TYPHOID • are systemic disease, • caused by the bacteria Salmonella typhi, • humans are the only reservoir, • humans can carry the bacteria in the gut for very long times (chronic carriers), and transmit the bacteria to other persons (either directly or via food or water contamination), • incubation period: 1-2 weeks, • high fever, malaise, cough, rash and enlarged spleen develops (intestinal perforation and haemorrhage may occur), • untreated (x ATB) has a 10% death rate. • vaccines : 1. inactivated (polysaccharid) vaccine (inj.), 2. live, attenuated (weakened) vaccine which is taken orally, 3. combined typhoid/hepatitis A vaccine. HEPATITIS A • caused by the hepatitis A virus (HAV)., • usually transmitted through the fecal-oral route or by contaminated food or water, • most adults - symptoms, including fatigue, low appetite, stomach pain, nausea, and jaundice, that usually resolve within 2 months of infection, • most children less than 6 years of age do not have symptoms or have an unrecognized infection, • Ig produced in response to hepatitis A infection last for life and protect against reinfection, • inactivated single-antigen hepatitis A vaccines (HAVRIX), live vaccine and combination vaccine A + B (TWINRIX). Vaccines in research pipelines Vaccines Against Viral Diseases • Dengue Fever Prevention • Ebola Vaccines • Hepatitis Disease-Specific Research • HIV Vaccine Development • Influenza Vaccines • MERS and SARS Therapeutics and Vaccines • Respiratory Syncytial Virus (RSV) Prevention • Smallpox Vaccine Supply and Strength • West Nile Virus Vaccines • Zika Virus Vaccines Vaccines Against Bacterial and Parasitic Diseases • Cholera Treatment and Prevention • Group A Streptococcus Vaccine Research • Lyme Disease Vaccines • Pertussis Vaccines • Tuberculosis Vaccine Development • Leishmaniasis Vaccines • Malaria Prevention, Treatment, and Control Strategies FOR X AGAINST? TAKE AWAY MESSAGE… • Vaccines are safe and effective. •Any vaccine can cause side effects. • Serious side effects from vaccines are extremely rare. •Getting vaccinated is much safer than getting the diseases vaccines prevent. ANTIVACCINATION MOVEMENT – WHY? AntiVaxxer • A person who thinks they know more about medicine and public health than the overwhelming majority of doctors, scientists, immunologists, and every major health organization across the whole entire planet. • Pfffft, I don't need to believe in "evidence based medicine" & fancy "science" made up by sheeple and shills! I'm an arrogant anti-vaxxer! (https://www.urbandictionary.com) https://measlesrubellainitiative.org/anti-vaccination-movement/