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"Approved" on a methodical conference department of infectious diseases and epidemiology " " __________ 2008 Protocol № Сhief of dept, professor V.D. Moskaliuk METHODOLOGICAL INSTRUCTIONS To a fifth year student of the Faculty of Medicine On independent preparation for practical training Topic: Host immunity. Immune response. Vaccines and serum. Specific Prophylaxis of Controllable Infections. Subject: Major: Educational degree and Qualification degree: Year of study: Hours: Prepared by Еpidemiology Medicine Specialist 5 6 Sydorchuk A.S., MD., PhD. 1. Theme: Host immunity. Immune response. Vaccines and serum. Specific Prophylaxis of Controllable Infections. 2. Lesson duration: 6 hours. 3. Training purpose: 3.1. A student must know: - Basic stages of historic development in specific prophylaxis; - Common concept about immunity, its kinds; - Medicines for active and passive immunisation, their comparative characteristics; - Calendar of prophylactic immunization; - Requirements of bacterial preparations, their storage; - Organisation of prophylactic vaccination, their stages, kinds of inoculation; - Principles of planning prophylactic immunization; - Equipment of room for vaccinal prevention; - Indications and contraindications for vaccination (absolute and temporary); - Modes and ways of vaccination by vaccines, anatoxins, serum and immunoglobulins; - Methods of efficacy assesment of vaccination; - Possible postvaccinal reactions and complications; - Registration of immunisation and its complications. 3.2. A student must be able to: - Give a talk about importance of vaccination among people of community; - Choose a contingent of people for vaccinal prevention; - Fill in form for application at SES for immunopreparations; - Select nesessary preparations for active or passive immunisation; - Carry out rejection of immunobiological medicines; - Realize previous screening of contingent who will be vaccinated for exposure contraindications; - Conduct inoculations with vaccines and anatoxins; - Apply homologous and heterologous sera, immunoglobulins; - Appreciate status of vaccinated in moment and after inoculation for timely exposure of possible reactions and complications; - Provide urgent medical care in case of complication; - Fill in correct forms according to order # 48 and report about carried out vaccinations; - Determine indications and persons for urgent vaccinal prevention; - Make up the common nonspecific and spesific urgent vaccinal prevention. 3.3. A student must posses practical skills: - Conducting of preparing educational talking among population; - Examination screening of people will be vaccinated (questioning, taking their temperature, checkup skin and mucous, investigation of blood circulatory system, respiratory and abdomen organs, urinary tract and nervous system); - Carry out vaccinal prevention by the usage of supracutaneous, subcutaneous, intramuscular, intranasal and oral vaccines; - Fulfill parenteral injection of heterogenous serum and immunoglobulins by the modified method of Bezredko; - Appreciate efficacy of vaccination, their possible side effects and complications. 4. Advices for students. An immune system is a collection of mechanisms within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own healthy cells and tissues in order to function properly. Detection is complicated as pathogens adapt and evolve new ways to successfully infect the host organism. To survive this challenge, several mechanisms have evolved that recognize and neutralize pathogens. Even simple unicellular organisms such as bacteria possess enzyme systems that protect against viral infections. Other basic immune mechanisms evolved in ancient eukaryotes and remain in their modern descendants, such as plants, fish, reptiles, and insects. These mechanisms include antimicrobial peptides called defensins, pattern recognition receptors, and the complement system. More sophisticated mechanisms, however, developed relatively recently, with the evolution of vertebrates. The immune systems of vertebrates such as humans consist of many types of proteins, cells, organs, and tissues, which interact in an elaborate and dynamic network. As part of this more complex immune response, the vertebrate system adapts over time to recognize particular pathogens more efficiently. The adaptation process creates immunological memories and allows even more effective protection during future encounters with these pathogens. This process of acquired immunity is the basis of vaccination. Prophylactic measures carry out independently of epidemic foci of infectious diseases and directed to prevention of infections. Measures are complex and directed to 3 sections of epidemic process: sources of infection; mechanism of transmission; receptive organism. Measures directed to 3 section of epidemic process include of vaccination. Vaccination plays a big role in prevention of airborne infections and infections of external covers (tetanus). Why? Airborne infections characterize: easy mechanism of transmission. It is difficult to isolate source of infections and to disinfect mode of transmission; immunity after vaccination or disease forms long and stable (measles, chickenpox, diphtheria). Efficiency of vaccination manifests in: decrease of sick rate; decrease of lethality. Vaccination is carried out in different countries and shown its efficiency. So, World Health Organization worked out Wide Immunization Program (WIP). Aim of this program is decrease of sick rate, lethality from infections and liquidation of infections in the world. Working out of WPI began in1974 and its realization – in 1974. At that time in developing countries from 90 mln born children 2,5 mln died from measles, 1 mln – from tetanus, 1 mln – from poliomyelitis, 50-60 thousand – from diphtheria, 30 thousand – from tuberculosis in the first three years. According to this program every government composes national calendar plan of vaccination and carries out vaccination against 6 infections: tuberculosis; poliomyelitis; diphtheria; measles; tetanus; whooping cough (pertussis); Vaccination results in decrease of sick rate from 20-30% till 100% (f.e. smallpox is liquidated in the world). Task of this program is liquidation of poliomyelitis in 2000. Government may add vaccination against other infections in dependence on social-economic and epidemiological situation (f.e. in RK vaccination against viral hepatitis D, epidemic parotiditis occur). Ukraine has order N 48 from 2006 “About ratification of order in usage of immunobiologic preparations and instruction of vaccination”. There are natural and artificial immunity. Natural acquired immunity (active) results in after infections and fractional immunization (when antigens get into organism through skin and mucosal membranes and in organism antibodies appear – brucellosis). Natural acquired (passive) immunity results in getting of antibodies through milk or placenta from mother to child. Passive artificial immunity results in introduction of plasma. Tutor should pay attention of students to kinds of vaccines and factors influenced on efficiency of vaccination. There are different vaccines for forming of active artificial immunity in medicine. The following are the next vaccines: 1. Corpuscular vaccines – I generation; 1. Chemical vaccines – II generation; 2. New perspective vaccines – III generation. Corpuscular vaccines are live and inactivated. Live vaccines are more effective because: Advantages: 1. Post vaccinal immunity is long and stable (causative agent imitates infectious process); 2. Vaccines are cheap; 3. Vaccines are introduced by different ways and once. Disadvantages: - microbes may restore its virulency; - microbes may cause disease in weak organism;- microbes must storage in special conditions – “cold chain”. Live vaccines are smallpox vaccine, poliomyelitis vaccine, epidemic parotiditis vaccine, measles virus vaccine, Bacillus CalmetteGuerin (BCG) vaccine, flu virus vaccine, Brucella strain 19 vaccine, tularemia vaccine, anthrax vaccine, plague vaccine, typhus vaccine, yellow fever vaccine, Qfever vaccine, tick borne encephalitis vaccine. Inactivated vaccines have advantages: vaccines do not cause diseases; stability in external environment. Disadvantages: immunity, caused inactivated vaccines is less stable and long; vaccines are introduced by hypodermic way; vaccines are introduced several times. Inactivated vaccines are whooping cough vaccine, typhoid vaccine, rabies vaccine, leptospirosis vaccine, flu virus vaccine, and herpes virus vaccine. Chemical vaccines are antigens of microbes releasing from accompanying substances by ultrasound and etc. Advanteges: vaccines do not have ballast which may cause side-effects. Disadvanteges: immunity is less stable. Chemical vaccines are meningococcic infection vaccine, typhoid fever vaccine, Brucella strain 19 vaccines, cholera vaccine, typhus vaccine, flu virus vaccine, and plague vaccine. Anatoxins are harmless toxins of microbes. There are diphtherial, botulinic, tetanic, staphylococcal, and gangrenous anatoxins. New vaccines are from ribosomes (diphtheria, salmonellosis; genicengineering (viral hepatitis B); synthetic, antiidiopathic, subunited (flu, viral hepatitis B). Serums and -globulin are use for formed of passive immunity. There are corresponding or homologous (from serum of people) and geterogenous (from blood of immunized animals) serums and -globulin. Geterogenous serums and globulin introduced by method of fractional introduction (Bezredka). Diluted 1:100 serum is introduced by inter dermal way to flexion surface of forearm in dose 0,1 ml. Reaction is defined in 20 min. If diameter of hyperemia and infiltration is less 1-sm test is negative. If diameter of hyperemia and infiltration is more 1-sm test is positive. If test is negative 0,1 ml of serum is introduced by sub dermal way. If in 20 min test is negative all dose of serum may introduce intro muscular. Medical observation longs for hour. If test is positive: - steroids are introduced intro muscular (30 mg); - diluted (1:100) serum is introduced by sub dermal way in doses 0,5; 2,0; 5,0 ml with interval 20 min. If test is negative 0,1 ml of serum is introduced by sub dermal way. If in 20 min test is negative all dose of serum may introduce intro muscular. Positive side of serum prophylactics is fast forming of immunity (in intro venous – immediately, in intro muscular – in 12-24 hours after injection. Negative side of serum prophylactics is short timed of immunity (geterogenous make immunity for 1-2 weeks, corresponding – 4-5 weeks). Serums may be antitoxic, antiviral, antimicrobal. Antitoxic serums contain antitoxins (tetanus, botulism, gas gangrene, snake poisons). Bacteriophages are viruses of bacteria that cause their lysis. There are next phases: 1. Adsorbtion of phages parts on cell’s wall of bacteria; 2. Penetration of phage into cell; 3. Duplication of phages in cells; 4. Destruction of cell. There are typhoid bacteriophage, salmonellosis bacteriophage, dysentery bacteriophage, staphylococcal bacteriophage, streptococcal bacteriophage, and other. Methods of vaccines introduction. There are parenteral, enteral, and aerosolic methods of vaccine introduction. Parenteral introduction includes of: epidermic (smallpox, plague, tularemia, anthrac); intradermic (tuberculosis, tularemia, inactivated vaccines); hypodermic – corpuscular, chemical, anatoxins, measles, epidemic parotiditis vaccines); intramuscular – APDT, serums, -globulins); intravenous - (antitoxic serums - gangrene); needleless – (flu, cholera). Enteral remedies are poliomyelitis, bacteriophages. Aerosolic introduction is used for revaccination. Intranasal mode of introduction occurs in flu vaccine, introduction of interferon. Factors influenced on efficiency of vaccination: 1. Quality of vaccines is immunogenity that connected with biological nature of microbe. F.e. antigen of smallpox is stable and smallpox immunity is stable; antigen of flu is changeable and immunity forms hardly; 2. Dose of vaccine that forms stable immunity defines in experiment. Little dose does not cause immunity, big dose may cause nonreactivity; 3. Contact of antigens with immune cells. It is necessary to introduce antigen 2-3 times (associated pertussis-diphtheria-tetanus vaccine – APDT – 3 times); 4. Interval between introducing of antigens defines by experiment (f.e. 1 month in APDT); 5. Every vaccine has own way of introducing – intravenous, intramuscular, intranasal etc. 6. Inclusion of population by vaccination. Normal inclusion is 90-95%. Kinds of vaccinations. There are primary vaccination and revaccination. Primary vaccination forms main or primary immunity. It may be single or repeated. Revaccination supports immunity on certain level that protects people from diseases. The following are the next vaccinations: planned and by epidemiological indications. Planned vaccination is carried out according national calendar. Vaccination by epidemiological indications is carried out in dependence on epidemiological situation (high level of sick rate etc.). It is very important to know about postvaccinal reactions and complications. Reactions may be early, nonspecific and specific; common and local. Common reactions may be light, middle, and heavy. Early reactions appear in period from several minutes to 2 hours after vaccination. Nonspecific reactions appear in period from 5-6 hours to 48 hours. Specific reactions appear in incubation (live vaccine) and in first 24 hours (in activated vaccines). Common reactions are high fever, headache, dizziness, nausea, vomiting, malaise, syncope, conjunctivitis, rashes, and catarrhal changes in rhinopharynx. Local reactions characterize by appearance of infiltrate, hyperemia, lymphangitis, and lymphadenitis. In intradermic and hypodermic introductions of vaccines local reactions develop in everybody. Sometimes after vaccination pathologic process may appear. They call postvaccinal complications. There are: 1. Complications from central nervous system (meningoencephalitis, encephalitis, poliomyelitis, polyneuritis) occur in introducing APDT; 2. Lesions of skin and mucosal membranes (rash, abscess, edema, phlegmon) in introducing of BCG; 3. Lesions of organs (myocarditis, glomerulonephritis) in introducing of APDT; 4. Development of anaphylactic shock and serous disease in repeated introduction of serums, in introducing of live vaccines; 5. Complications associated with breach of aseptic and antiseptic; 6. Sharpening of chronic and latent diseases (rheumatism, tuberculosis, nephritis). Also student must know about organization of vaccination. Now family doctor is responsible for vaccination and efficiency of vaccination is criteria of his work. Main directions of his work: 1. Composition of plane of vaccination. Plane of prophylactic vaccines and vaccines by epidemiologic indications on the next year is composed in November- December. It is necessary next information for composition: refined number of children according age; facts about birth rate in last 3 years; information about state of vaccination according national calendar; factors about number of professional groups and about territory where vaccines carry out. 2. Registration of vaccines. Every child must have card of vaccination, where facts about vaccination are seen. Cards are kept in collection of cards according to ages of birth and months. In every month vaccines are collected by kinds (diphtheria, measles etc.). Cards of children with contraindications and departured keep separately. 3. Organization of vaccination and observation for people getting vaccines. People are observed in hour after vaccination and in 24, 48, and 72 hours or according to instruction. 4. Preparing of children with allergy and other contraindications. There are constant and temporary contraindications. Medical contraindications according to order N 48: A. Common contraindications: 1. Anaphylactic (1), encephalitic or strong reactions on preceding dose of vaccine (for all vaccines) (2). 2. Immunodeficiency (for live vaccines): - primary; - caused by leukosis, lymphoproliferative diseases or immunodepressive therapy (3); - caused by steroids (prednisone) in high doses (more then 2 mg/kg and more then 7 days (4); 3. Pregnancy (for live vaccines); 4. Middle and heavy diseases accompanied by fever or breaches of general condition (5). Notes: 1) in allergy to components of vaccine analogous vaccine out of these components are used; 2) strong reactions are long convulsions, collapses, piercing shout, fever 39,5C for APDT. It is necessary to decide question about vaccination with APDT or ADT; 3) vaccination carries out in 6 months after immunodepressive therapy; 4) vaccination carries out in 3 months after treatment; 5) vaccination carries out after recovery or achievement of total or particular remission. B. These states are not contraindications: not heavy common (T-39,5C) and local reactions on preceding dose; light diseases with T-38C or diarrhea; flowing antibacterial therapy or recovery; treatment with steroids – local, inhalation or low doses (2mg/kg) or short course (less 7 days); prematurety; pregnancy of mother or other relations; having of infections; frequent acute respiratory diseases; nurse; allergy on food, drugs; bronchial asthma, atopical dermatitis, eczema; chronic diseases of heart, lungs, kidneys. Contraindications for individual vaccines. BCG vaccine: - prematurety (weight less 1500 and age less 23 weeks) (6); generalized BCG in other children in family (possibility of hereditary immuno deficiency). Revaccination: - having tuberculosis; - keloid on first dose of BCG; HIV-infection with clinical features. APDT: - progressive neurological pathology. ADT and ADT-M: - not contraindications (7). OPV: - immuno deficiency among members of family (8); - HIV-infection. Measles: - not contraindications. Epidemical parotiditis: - not contraindications. Notes: 6) these children get vaccine before discharging from hospital or maternity hospital; 7) ADT-M is not use for primary vaccination; 8) if Ig or preparations of blood are introduced vaccination carries out after 3 months; if child did not get “O” dose in maternity hospital he must get 4 dose of OPV with measles vaccination in 1 year. 5. Control questions: 1. Stages of vaccination history, first vaccines. 2. Kinds of immunity. 3. Types of immune medicines for active and passive immunoprophylaxis. 4. Schedule and card of prophylactic immunization. 5. Requirements of bacterial preparations, their storage. 6. Principles of planning prophylactic immunization. 7. Equipment of room for vaccinal prevention. 8. Tactics of physician in case of anaphylactic shock. 9. What vaccines are used to prevent infectious diseases? 10. Name the methods by which vaccines are administered. 11. What is vaccination and revaccination? 12. Name the main contraindications for prophylactic vaccination. 13. Who can perform vaccination? 14. What are the causes of postvaccination complications? 6.0. Literature. 6.1. Basic: 1. Lecture 2. Epidemiology and Fundamentals of Infectious Diseases. M.L. Volovskaya. Mir Publisher. Moscow.