Principle of Vaccinology Elham Ahmadnezhad MD MPH Ph

Principle of Vaccinology Elham Ahmadnezhad MD. MPH. Ph. D Student of Epidemiology Farshid fayyaz Jahani MD. MPH. Specialist in Infectious Disease & Tropical Medicine Tehran University of Medical Sciences 10/10/2011 Vaccinology. 1

Brief History of Lecturers • Elham & Farshid from Tehran, Iran are couple since 3 years ago (2008). Farshid graduated from Medical School in Infectious disease and Tropical medicine’ specialist and Elham now senior student in Ph. D of Epidemiology. • They have common interest in infectious disease epidemiology then developed some lecturers such as this (Vaccinology). Hope it’s useful for all target groups. Our Email: farshid. fayyazjahani@gmail. com & elhamahmadnezhad@gmail. com 10/10/2011 Vaccinology. 2

OUTLINE Introduction & Definition Vaccination policy option Mass Vaccination Surveillance System of Vaccination Vaccine Development Vaccine Evaluation Vaccine Safety Reporting Immunizations Reliable Web sits Vaccine Training Course Review of National Immunization Coverage 10/10/2011 Vaccinology. 3

What is Vaccine • Dictionary (Dorland 30 th edition 2008) Ø Attenuated or killed microorganisms or proteins derived from them, administered for the prevention, treatment, or amelioration of infectious diseases • Wikipedia Ø A vaccine is a biological preparation that improves immunity to a particular disease. A vaccine typically contains an agent that resembles a disease-causing microorganism, and is often made from weakened or killed forms of the microbe. The agent stimulates the body's immune system to recognize the agent as foreign, destroy it, and "remember" it, so that the immune system can more easily recognize and destroy any of these microorganisms that it later encounters. 10/10/2011 Vaccinology. 4

What is Vaccinology? • Vaccinology is the science of developing vaccines to prevent diseases 10/10/2011 Vaccinology. 5

Vaccines-Historical Perspective • 7 th century Indian Buddhists' drank snake venom to protect against snake bite. • 10 th century Variolation to prevent smallpox in China and Turkey. • Early 1700 s Variolation introduced into England. • 1760 -70 The Jennerian era. • 1875 -1910 Dawn of Immunological Science. • 1910 -30 Early bacterial vaccines, toxins and toxoids. • 1930 -50 Early viral vaccines: yellow fever and Influenza. • 1950 -1970 The tissue culture revolution: poliomyelitis, measles, mumps and rubella. • 1970 -1990 Dawn of the molecular era: hepatitis B, Streptococcus pneumonia, Hemophilus influenza B. • Today Glycoconjugate vaccines, rotavirus vaccine, human papilloma virus vaccine and herpes zoster vaccine. 10/10/2011 Vaccinology. 6

Aims of Immunisation Programmes • • To protect those at highest risk (selective immunisation strategy) or To eradicate, eliminate or control disease (mass immunisation strategy) Currently, it is estimated that vaccination saves the lives of 3 million children a year • Eradication Ø Infection (pathogen) has been removed worldwide e. g. smallpox • Elimination Ø Disease has disappeared from one area but remains elsewhere e. g. polio, measles • Control Ø Disease no longer constitutes a significant public health problem e. g. neo-natal tetanus 10/10/2011 Vaccinology. 7

Vaccines Achievements 1 • With sanitation and nutrition, vaccines are hailed as one of the most important public health achievements of the 20 th century. • The history of vaccinology lends itself to discussion of its progress in terms of periods or eras, in which new advances were made. • Once only targeted against serious childhood diseases, vaccinology has become a tool for preventing infectious diseases or their complications and outcomes in all age groups. • This has seen the number of vaccine-preventable diseases rising to around 26. 10/10/2011 Vaccinology. 8

Vaccines Achievements 2 • “At the end of the 20 th century the US Centers for Disease Control and Prevention (CDC) cited vaccination as the number one public health achievement of that century” • “The elimination in 1977 of smallpox as a human disease must rank as one of the major achievements of modern medicine” 10/10/2011 Vaccinology. 9

The Ideal Vaccine • Immunogenic • Long lasting immunity • Safe • Stable in field conditions • Combined • Single dose • Affordable (and accessible) to all 10/10/2011 Vaccinology. 10

Categorization of Current Vaccines • Live attenuated: Viruses (oral polio, measles, mumps, rubella, yellow fever), Bacteria (BCG, cholera)- Long lasting immunity, very fragile (cold chain), mutation to pathogenicity • Killed Vaccines: Viruses (hep. A, Salk polio) Bacteria (pertussis, cholera)-intermediate immunity, several doses may be required • Sub-unit vaccines incl: Toxoids: (tetanus, hep b. , occellular vaccines), Conjugate polysacaride vaccines linked with suitable carrier proteins (Hib). Also single or polyvalent vaccines. 10/10/2011 Vaccinology. 11

Viral Vaccines 10/10/2011 Vaccinology. 12

Bacterial Vaccines 10/10/2011 Vaccinology. 13

Target Fungal Vaccines 10/10/2011 Vaccinology. 14

Target Parasitic Disease • Malaria • Trypanosomiasis • Leishmaniasis • Toxoplasmosis 10/10/2011 Vaccinology. 15

Selective Vaccination • Vaccine given specifically to those at increased risk of disease: • High risk groups Ø e. g. Pneumococcal vaccine • Occupational risk Ø e. g. Hepatitis B, influenza • Travellers Ø e. g. Yellow fever, rabies, meningitis • Outbreak control Ø 10/10/2011 e. g. Hepatitis A. vaccine, measles Vaccinology. 16

Pipelines for Developing Countries Much needed vaccines for the developing world • Malaria • Tuberculosis • HIV • Hookworm • Dengue • Enterotoxigenic Escherichia coli • Shigella 10/10/2011 Vaccinology. 17

More Possibilities • Therapeutic vaccines: Identification of specific tumor antigens provide immune targets for which immunogenic vaccines may conceivably be designed. Examples: Ø Leukemia Ø Breast cancer Ø Melanoma Ø Prostate cancer Ø Colon cancer • Vaccines against autoimmune diseases 10/10/2011 Vaccinology. 18

Similarities between Vaccines and other Drug • Vaccines are also medicines • Potential for adverse effects • Multiple ingredients • Potential for interaction with disease and other medicines • Also need to comply with standards of safety, efficacy and quality 10/10/2011 Vaccinology. 19

Vaccination Policy Options Eradication Activities ? New Vaccine Introduction Newer Vaccine Research and Development Outbreak vs. routine control of epidemic diseases 10/10/2011 Vaccinology. 20

Role of disease burden studies in the development and introduction of new and underutilized vaccines Vaccine Design Clinical Evaluation • Study sites • Vaccination schedules & Strategies Vaccine Utilization • Target groups • Impact • Cost-effectiveness Disease Epidemiology • Geographical distribution • Age groups • Seasonality, risk factors Disease-Burden Studies 10/10/2011 Vaccinology. 21

Mass Vaccination Objective: Make hosts resistant to infection without having to experience disease 10/10/2011 Vaccinology. 22

Impact of Mass Vaccination Programmes • Reduce size of susceptible population • Reduce number of cases Ø Reduce risk of infection in population Ø Reduce contact of susceptible to cases Ø Lengthening of epidemic cycle -> honeymoon phase Ø Increase in mean age of infection 10/10/2011 Vaccinology. 23

No Mass Vaccination Each host in contact with infected host becomes infected (with a certain probability) 10/10/2011 Vaccinology. 24

Mass Vaccination Outbreak attenuated (or averted) by lack of susceptible hosts 10/10/2011 Vaccinology. 25

Impact of Mass Immunisation Programme Annual measles notifications & vaccine coverage Poland 1960 -2000 10/10/2011 Vaccinology. 26

Surveillance of Vaccine Preventable Disease • Vaccine uptake • Vaccine effectiveness • Serological surveillance • Adverse events • Knowledge and attitudes • Vaccine uptake • Disease incidence 10/10/2011 Vaccinology. 27

Objectives of Surveillance Vaccine Preventable Diseases • Pre-implementation Ø Estimate burden Ø Decide vaccination strategy • Post implementation Ø Monitor impact and effectiveness • Nearing elimination Ø Identify pockets of susceptible Ø Certification process 10/10/2011 Vaccinology. 28

Disease Incidence • Main sources of data Ø Statutory notification Ø Laboratory reporting Ø Death registrations • Other sources Ø Hospital episodes Ø Sentinel GP reporting Ø Paediatric surveillance 10/10/2011 Vaccinology. 29

Measles Case Definitions • Suspect case Ø Rash and fever • Probable case Ø Rash, fever, and either: cough, coryza or conjunctivitis • Laboratory confirmed • Saliva/serum Ig. M positive 10/10/2011 Vaccinology. 30

Predictive Value of Notified Measles Effect of Change in Incidence 10/10/2011 Vaccinology. 31

Surveillance of Vaccine Coverage • Vaccine distributed • Vaccine administered Ø Sampling population assessment e. g. Cluster Ø Total population assessment (administrative) Number of doses of vaccine given/used Total (target-)population 10/10/2011 Vaccinology. 32

Use of Administrative Coverage Data • Usually total population • Monitor trends over time • Look for pockets of poor coverage • Compare with disease epidemiology • Estimate vaccine effectiveness 10/10/2011 Vaccinology. 33

Steps on Vaccine Development 1 • Recognize the disease as a distinct entity • Identify etiologic agent • Grow agent in laboratory • Establish in animal model for disease • Identify an immunologic correlate for immunity to the disease- usually serum antibody • Inactivate or attenuate the agent in the laboratory- or choose antigens • Prepare candidate vaccine following GOOD manufacturing Procedures • Evaluate candidate vaccine(s) for ability to protect animals 10/10/2011 Vaccinology. 34

Steps on Vaccine Development 2 • Prepare protocol( protocol s) for human studies • Apply to MCC for investigational New drug (IND) approval • Phase I human trials- Safety and immugenicity, dose response • Phase II trials- Safety and immugenicity • Phase III trials- Efficacy 10/10/2011 Vaccinology. 35

Steps on Vaccine Development 3 • Submit Product Licensure Application MCC approval • Advisory Committees review and make recommendations • Marketing Post- Licensure Surveillance for safety and effectiveness (Phase IV) IV • Long and Complicated process Ø Usually takes 1010 15 years Ø Many vaccine candidates fail for every success Ø Costs: $ 100100 $ 700 million per successful vaccine 10/10/2011 Vaccinology. 36

Vaccine Evaluation Post-licensing Pre-licensing Observational Studies Randomised, Blinded, Controlled Clinical Trials Vaccine effectiveness: Protective Effect under Ordinary Conditions of a public health programme Vaccine efficacy: Protective Effect under Idealised Conditions RCT: controlled experiments, simple interpretation 10/10/2011 Vaccinology. prone to bias, more complex interpretation 37

Efficacy, Effectiveness, Impact and Herd Immunity • Efficacy is the direct protection to a vaccinated individual as estimated from clinical trial • Effectiveness is an estimate of the direct protection in a field study post licensure. • Herd Immunity is an indirect effect of vaccination due to reduced disease transmission. • Impact is the population level effect of a vaccination programme. This will depend on many factors such as vaccine coverage, herd immunity and effectiveness. 10/10/2011 Vaccinology. 38

Basic Calculation of VE % reduction in attack rate of disease in vaccinated (ARV) compared to unvaccinated (ARU) individuals Where VE (%) = (ARU-ARV) X 100 ARU and Consequently, VE = 1 -RR (preventive fraction) 10/10/2011 Vaccinology. 39

Basic Calculation of VE Vaccinated IV = 2/10 = 0, 2 Unvaccinated IU = 9/10 = 0, 9 – 0, 2 VE = 10/10/2011 0, 9 Vaccinology. = 78% 40

Methods to Assess VE • Pre-licensure: Ø Randomised control trial (RCT) • Post-licensure: Observational/Field investigation 10/10/2011 • Screening method • Cohort study • Household contact study • Case-control study Vaccinology. 41

Observational study: Screening Method • Used with Routine Surveillance Data Ø Take population vaccine coverage (PPV) PPV Ø Compare with coverage in cases (PCV) PCV VE = 1 - PCV x (1 -PPV) (1 -PCV) x PPV 10/10/2011 Vaccinology. 42

Observational study: Screening Method Relationship between VE, PPV and PCV Proportion of cases vaccinated 1 0. 8 0. 6 VE=60% VE=80% 0. 4 VE=90% VE=95% 0. 2 0 0. 5 0. 6 0. 7 0. 8 0. 9 1 Proportion of population vaccinated 10/10/2011 Vaccinology. 43

Potential Pitfalls. . • Case definition; • Vaccine history; • Case ascertainment; • Comparability of vaccinated/unvaccinated groups. 10/10/2011 Vaccinology. 44

Methodological Issues: Case Definition 1 • Lower specificity: Case definition based only on clinical criteria may result in false-positive diagnoses àARV > ARU VE (%) = (ARU-ARV) X 100 ARU àartificial reduction in VE 10/10/2011 Vaccinology. 45

Methodological Issues: Case Definition 2 Changes in MUMPS vaccine effectiveness ARV ARU VE Case definition Diagnosis by school nurse 18% (12/67) 28% (77/272) 37% 89 25% (68/272) 52% Kim Farley et al 1985 AJE 10/10/2011 Vaccinology. 46

Methodological Issues: Case Definition 2 Changes in MUMPS vaccine effectiveness ARV ARU VE Case definition Diagnosis by school nurse Parotitis > 2 days 18% (12/67) 12% (8/67) 28% (77/272) 25% (68/272) 37% 52% Kim Farley et al 1985 AJE 10/10/2011 Vaccinology. 47

Methodological issues: Vaccine History Ascertainment • Avoid misclassification of vaccination status • Equal effort to confirm vaccination status amongst cases and non-cases Ø Vaccination histories should be documented using GP, clinic, hand-held or computer records Ø Persons with missing vaccination records should be excluded 10/10/2011 Vaccinology. 48

Vaccine effectiveness: Post licensure monitoring of VE Post-licensure: maintenance of VE • Problems in vaccine delivery Ø Cold chain failure, schedule violation, n° of doses, vaccine strain substitution • Epidemiological factors Ø Pathogen changes • Methodological bias Ø Selection bias, confounding, chance effects • Low protective efficacy Ø Bad batch, different target population, alternative patterns of use, vaccine strain used 10/10/2011 Vaccinology. 49

Summary of VE • Multiple sources of data are valuable to evaluate vaccine programmes • Source of data and case definitions change with stage of vaccination programme • Monitoring VE is integral • VE can be carefully estimated from routine data 10/10/2011 Vaccinology. 50

Let’s GO An Example 10/10/2011 Vaccinology. 51

A Randomized, Controlled Experiment • 400, 000 elementary school students participated in the experiment. • 200, 000 chosen at random from 400. 000 in the treatment group got the vaccine. • The remaining 200, 000 in the control group did not get the vaccine. 10/10/2011 Vaccinology. 52

A Randomized, Controlled Double-Blind Experiment • The 200, 000 children in the control got a fake vaccination called a placebo. • The children and their parents were not told if they got the real vaccine or not. • Even the doctors and nurses didn’t know; only the statisticians knew 10/10/2011 Vaccinology. 53

Experimental Results Size Rate Treatment 200, 000 28 Control 200, 000 71 Total 400, 000 99 Looks promising but is it significant? 10/10/2011 Vaccinology. 54

Analysis: The Devil’s Advocate • Let’s play the devil’s advocate. Let’s assume the vaccine has no effect. • Then the 99 cases of polio were split into the two groups purely at random. • Is it very likely only 25 fall in the treatment group? 10/10/2011 Vaccinology. 55

A Probability Model • Put 400, 000 balls in an urn with 99 black and the rest white. • Draw 200, 000 (for the treatment group) and count the number of black balls. • What is the chance of a split as extreme or more extreme than 28 in the treatment group and 71 in the control group. • About one in a billion 10/10/2011 Vaccinology. 56

Calculating Probabilities • A statistician relies on theory of probability to calculate probabilities. • The number of black balls X in the treatment group follows the hypergeometric distribution. • 10/10/2011 Vaccinology. 57

Conclusion: Get vaccinated! • We must reject the hypothesis that the treatment has no effect; otherwise we must believe we are incredibly unlucky. • We can therefore recommend mass vaccination. • We also note a vaccination does not prevent polio. Your best protection is to get vaccinated and encourage everyone to be vaccinated. 10/10/2011 Vaccinology. 58

Vaccine Safety 10/10/2011 Vaccinology. 59

Today’s Agenda • The Good Ø The benefits of vaccination Ø Ongoing safety monitoring • The Bad Ø Vaccines “rocky” past Ø Acceptable risk? • And the Ugly Ø Wealth of misinformation Ø Vaccine refusal 10/10/2011 Vaccinology. 60

Vaccines Work JAMA 2007 298(18)2156 -2163 MMWR August 22, 2008 903 -913 10/10/2011 Vaccinology. 61

Pre-licensure Safety Monitoring 1 10/10/2011 Vaccinology. 62

Pre-licensure Safety Monitoring 2 • Vaccine Adverse Event Reporting System (VAERS) Ø Limitations • Vaccine Safety Datalink (VSD) Ø Established in 1990 by CDC and 8 HMOs Ø Database on 8. 8 million lives 10/10/2011 Vaccinology. 63

Safety Monitoring Who looks at all that data? • • Institute of Medicine (IOM) Part of the National Academy of Science Non-profit, non-governmental organization, volunteer Provide the CDC, NIH and congress on data interpretation on matters of bio-medical science IOM Vaccine Safety Reports – The “Gold Standard” in vaccine safety analysis Ø Ø Ø Ø 10/10/2011 MMR and Autism (2001) Thimerosal and Neurodevelopmental Disorders (2001) Multiple Immunizations and Immune Dysfunction (2002) Hep. B Vaccine and Demyelinating Neurological Disorders (2002) SV 40 Contamination of Polio Vaccine and Cancer (2002) Influenza vaccines and Neurological Complications (2003) Vaccines and Autism (2004) Vaccinology. 64

The Bad • The Cutter IPV incident (1955) • Vaccine associated paralytic polio • Swine flu vaccine and GBS (1976 -7) 10/10/2011 Vaccinology. 65

The Cutter Incident • 1950 s Jonas Salk pioneering work with IPV • 5 companies stepped forward to manufacture IPV after licensure • Cutter (the smallest) made a bad batch Ø 100, 000 children injected with live virus Ø 70, 000 got mild polio Ø 200 were permanently paralyzed Ø 10 died 10/10/2011 Vaccinology. 66

Vaccine-Associated Paralytic Polio (VAPP) • OPV is a live attenuated virus • 1 out of 2. 4 million doses VAPP • 1997 a IPV/OPV schedule • 2000 an all IPV schedule recommended 10/10/2011 Vaccinology. 67

“Swine Flu” vaccine of 1976 -1977 • Increased risk of Guillain-Barré syndrome (GBS) • Risk period was 6 -8 weeks after vaccine and most >25 yrs of age • Incident of 1 per 100, 000 • Above the background rate of 0. 87 per million persons in a 6 week period 10/10/2011 Vaccinology. 68

“Acceptable” Risk? • Local side effects Ø Swelling, redness • Systemic side effects Ø Fever, pain, allergic reaction • MMR and Thrombocytopenia • MMR(V) and febrile seizures • Adolescent vaccines and syncope • Guillain-Barré and MCV 4 10/10/2011 Vaccinology. 69

MMR & Thrombocytopenia • Yes • 1 in 40, 000 at 12 -23 months • Less common than after natural disease Journal of Autoimmunity 2001 16: 309 -18 10/10/2011 Vaccinology. 70

MMR(V) & Febrile Seizures • 10% develop fever after 1 st MMR dose • Febrile Seizure Risk 4 cases / 10, 000 doses MMR + V 9 cases / 10, 000 doses MMRV MMWR 2008 57: 258 -60 10/10/2011 Vaccinology. 71

Syncope and Adolescent Vaccines MMWR May 2, 2008 / 57(17); 457 -460 10/10/2011 Vaccinology. 72

Guillain-Barré Syndrome and MCV 4 • MCV 4 (Menactra®) licensed in Jan 2005 • Sept 2005 alert by FDA/CDC: Ø 2. 5 million doses Ø 5 cases of GBS in month following vaccine (VAERS data) 10/10/2011 Vaccinology. 73

and the Ugly • Wealth of misinformation ØMMR and Autism ØMercury poisoning ØVaccines overwhelming the immune system • Vaccine refusal 10/10/2011 Vaccinology. 74

Reporting Immunization Requirements • Documenting administration of vaccine • Documenting record of immunization 10/10/2011 Vaccinology. 75

Reporting immunization requirements: Documenting administration of vaccine Content • Name and address of vaccine • Medicare number • Date of birth and gender • Date of administration • Name and lot number of vaccine • Name of immunizer • Other data as required 76 10/10/2011 Vaccinology. 76

Reporting immunization requirements: Documenting administration of vaccine Content-Lot Number 3 lot numbers on packaging: § On antigen carton § On adjuvant carton § On shoe box Document lot number on shoe box. 77 10/10/2011 Vaccinology. 77

Immunization Practice Standards • Vaccine management • Informed consent • Administration of vaccine • Documentation • Anaphylaxis management • Reporting of adverse events 10/10/2011 Vaccinology. 78

Immunization practice standards: Vaccine management-Storage and handling of vaccine • Cold chain system • Control procedure/mechanism/equipment ØVaccine fridge ØDialer and data logger ØVaccine coolers ØCold and warm marks or minimum-maximum thermometers • Cold chain breach 79

Immunization practice standards Informed consent • Parental consent required for individuals • less than 16 years old • Risk vs. benefits (of receiving vaccine or not) • General info about vaccine and potential side effects • Ensure info is well understood • Allow opportunities for questions • Assess health with screening questions • Document informed consent 10/10/2011 Vaccinology. 80

Immunization practice standards Informed consent Screening Questions (Examples) • Is unwell today? • Has history of severe life-threatening allergy to Ø Eggs Ø Previous dose of the vaccine; or Ø Any of its components • Past history of Guillain Barre Syndrome • Has disease or treatment lowering immunity • Has severe bleeding disorder 10/10/2011 Vaccinology. 81

Immunization practice standards Administration of vaccine Intramuscular injection IM in vastus lateralis (Birth to 18 months) IM in deltoid (18 mths and over) 10/10/2011 Vaccinology. Source : http: //www. health. gov. nl. ca/health/publications/immunization/S 4/ 82

Immunization practice standards Administration of vaccine Post-vaccination • Check Ø For bruising, redness, swelling Ø Client for any adverse event • Instruct client Ø To wait 15 minutes Ø Of possible side effects and what to do Ø To call if adverse event in next 4 weeks Ø Need for a second dose 10/10/2011 Vaccinology. 83

Immunization practice standards Documentation • Consent form: Pandemic H 1 N 1 Influenza Immunization • Client immunization record • Adverse event following immunization • CSDS – as directed 10/10/2011 Vaccinology. 84

Immunization practice standards Anaphylaxis management • Assess and manage ABCs • Call for help • Administer epinephrine • Call 115 • Repeat dose as needed • Document and share clinical info 10/10/2011 Vaccinology. 85

Immunization practice standards Reporting AEFI Current surveillance process • AEFI form to be completed by PH or physician • Form submitted to RMOH • PH enters data in CSDS and sends form to CDC Unit Immunizers: inform clients to call PH if severe or unusual reactions in the 4 weeks following vaccination. • CDC Unit faxes form to PHAC • Refer to NB Immmunization Handbook 86 10/10/2011 Vaccinology. 86

Immunization practice standards Reporting AEFI Enhanced severe AEFI surveillance • AEFI form to be completed by physician • May be completed by PH when reported to PH first • Form submitted to RMOH • PH enters data entered in CSDS and sends form to CDC Unit • Refer to GNB website for reporting process, case definition and form http: //www. gnb. ca/0053/h 1 n 1/audience_professionals-e. asp 87 10/10/2011 Vaccinology. 87

Immunization practice standards Reporting AEFI Enhanced severe AEFI surveillance Weekly active AEFI reporting • Internal medicine specialist and neurologists will submit weekly count of cases meeting case definition of 8 conditions along with DOB and name to CDC Unit via special email address. • CDC Unit will send the information to MOH. • Timely data to be used be regional PH to ensure complete reporting of AEFI. 88 10/10/2011 Vaccinology. 88

Immunization practice standards Occupational health issues • Used injection material Ø Handling Ø Disposal § Sharp containers Ø Where to place Ø When to replace Ø How to dispose of • Needle stick injury – refer to RHA policy • Use of personal protective equipment and infection control measures 10/10/2011 Vaccinology. 89

Reliable web sites 10/10/2011 Vaccinology. 90

CDC Vaccines and Immunization Contact Information • Telephone • Email 800. CDC. INFO nipinfo@cdc. gov • Website www. cdc. gov/vaccines • Vaccine Safety www. cdc. gov/od/science/iso 10/10/2011 Vaccinology. 91

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Promote Epidemiology Training & Research • WHO Advanced Training Course on Immunology, Vaccinology, and Biotechnology Applied to Infectious Diseases • Liaison with epidemiology training programmers Ø INCLEN, FETP, EPIET • WHO Collaborating Centers 10/10/2011 Vaccinology. 93

References • Geoffrey A. Weinberg and Peter G. Szilagyi. Vaccine Epidemiology: Efficacy, Effectiveness , and the Translational Research Roadmap. The Journal of Infectious Diseases 2010; 201 (11): 1607 -1610 • European Program for Intervention Epidemiology Training. Principle of Vaccinology. 2008 • EPI coverage survey, WHO. Available at: http: //www. who. int/immunization_monitoring/routine/EPI_coverage_survey. pdf. Access date: 10. 2011 • Geert Leroux-Roels, Paolo Bonanni, Terapong Tantawichien, Fred Zepp. Understanding Modern Vaccines: Perspectives in Vaccinology Vaccine development. Volume 1/ Issue 1/ 115 -150 • Thomas D. Szucs. Health economic research on vaccinations and immunization practices—an intro uctory primer. Vaccine 23 (2005): 2095– 2103 • NB Immunization Handbook, sections IV-III, IV-IV 10/10/2011 Vaccinology. 94