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Principles of Immunization in practice UGME phase 2 Delphine Grynszpan MD MPH FFPH dgrynszpan2mun.ca  General principles Uses of immunization Impact of vaccination Precautions & contraindications Outline Vaccination programs in practice...

Principles of Immunization in practice UGME phase 2 Delphine Grynszpan MD MPH FFPH dgrynszpan2mun.ca  General principles Uses of immunization Impact of vaccination Precautions & contraindications Outline Vaccination programs in practice Sources of information Vaccination programs in Canada Vaccine hesitancy Role of immunization Pre-exposure Prevention Herd immunity Individual Population Post-exposure Outbreak response prophylaxis Post-exposure 3 Passive Immunization Administration of preformed antibody to a recipient to boost their immunity. Post-exposure Immediate effect Short-term immunity 4 Passive immunizing agents Standard Immune Antitoxine (or antisera) Globulins Botulism antitoxin Measles, Hep A Diphtheria antitoxin Specific Immune Globulins most common: Hepatitis B (HBIG) Rabies (RIG) Tetanus (TIG) Varicella-Zoster (VZIG) 5 Active Immunization = Vaccination (use of vaccines) Administration of all or part of a micro-organism to evoke an immunologic response that mimics that of natural infection but usually presents little or no risk to the recipient. Usually pre-exposure Delayed effect Longer-lasting immunity 6 Impact of vaccination  Effectiveness of routine immunization Source: HealthCanada, 2014 & 2024 8 Precautions & contraindications  Contraindications & Precautions Anaphylaxis For live vaccines: Live attenuated vaccines: Significant immunosuppression MMR, varicella, MMRV LAIV (live attenuated influenza) Pregnancy Rotavirus Recent administration of live vaccine BCG Yellow fever Ty21a (typhoid) OPV (oral polio) Vaccine specific Conditions that are NOT contraindications to immunization No contraindication: Premature birth Breast feeding Concurrent antibiotic therapy Inactivated vaccines during pregnancy Investigate and accommodate if relevant: Common illnesses (delay if fever) Concerns regarding possible allergy Concerns regarding past adverse reactions Concerns regarding capacity to respond to vaccine 11 Vaccination programs  Designing vaccination programs Features of an effective vaccine Safe (Few side-effects) Protective (Sustained protection) Biological stability Ease of administration Affordable Cost-effective introduction of a new vaccine: Cost-effectiveness (harm/benefit) Ease of use/ of introduction Whole program in place! (distribution, records, surveillance) Focus General vaccination Targeted vaccination 13 Evidence base for vaccination programs Surveillance of CD Vaccine efficacy (development phases 1 to 3) Program effectiveness (phase 4) Surveillance of Adverse Events Following Immunization https://www.canada.ca/en/public- health/services/immunization/canadian- adverse-events-following-immunization- surveillance-system-caefiss.html  Types of vaccination programs Based on availability, harm/benefit & cost-effectiveness evaluation Mass vaccination programs Aim to vaccinate all population & obtain herd immunity May be rolled out initially by staggered targeted programs Targeted programs Aim to protect at risk sub-groups Most likely to vary from one jurisdiction to another Travel vaccination programs Focused on prevalence of disease abroad & likely exposer of individual traveler Case-by-case risk assessment 16  Vaccination guidelines National Advisory Committee on Immunization (NACI) https://www.canada.ca/en/public-health/services/immunization/national-advisory- committee-on-immunization-naci.html P/T health authorities NL: https://www.gov.nl.ca/hcs/publichealth/cdc/immunizations/ Canadian Immunization Guide (CIG): https://www.canada.ca/en/public-health/services/canadian- immunization-guide.html https://www.canada.ca/en/public-health/services/diseases.html?vaccine- preventable Travel vaccination: https://travel.gc.ca/travelling/health-safety/vaccines 17  Vaccination schedules in Canada Similar across Canada Can be some variation: Timing Introduction of new vaccines Population specific vaccination programs NL immunization schedule: https://www.health.gov.nl.ca/health/publichealth/cdc/immunizations.html Across Canada:https://www.canada.ca/en/public-health/services/provincial-territorial- immunization-information/provincial-territorial-routine-vaccination-programs-infants- children.html 18 19  Targeted vaccination Professional risk Risk group (age, comorbidity) Post-exposure vaccination At risk situation OR exposure to disease Sometimes combined with IgG In response to an outbreak / epidemic Catch-up vaccination (migrants, delay) 20  Adult Immunization in NL General population: Influenza Over 60 & at risk: Pneumococcal vaccine Herpes Zoster vaccine Boosters: Tdap every 10y and pregnancy 21  Travel vaccination Health Canada recommendations: https://travel.gc.ca/travelling/health-safety/vaccines Generally not covered by provincial programs Region & activity-based risk assessment May be required for entrance into country (eg. yellow fever) 22 Vaccine hesitancy  Reasons why people refuse/delay vaccination personal beliefs or philosophical reasons that minimal risk of contracting these diseases and easily treatable believe that natural immunity is better for their children that healthy diets and lifestyles are protective prefer to not put extra chemicals into their (or children’s) bodies vaccine content (eg: animal-derived gelatin; human fetus tissue in rubella) McKee C et al. Exploring the Reasons Behind Parental Refusal of Vaccines. J Pediatr Pharmacol Ther. 2016 Mar-Apr; 21(2): 104–109. 24  Reasons why people refuse/delay vaccination safety concerns Information from media, social media, friends/family Fear of short and long-term side effects; of giving too many shots at once desire for more information Healthcare provider not easy to talk to McKee C et al. Exploring the Reasons Behind Parental Refusal of Vaccines. J Pediatr Pharmacol Ther. 2016 Mar-Apr; 21(2): 104–109. 25 22  Reasons why people refuse/delay vaccination Access Distance, lack of transportation, disability Work, childcare, homecare Communication Language, culture, specific populations Internet access (familiarity & availability) Systemic discrimination Delphine Grynszpan [email protected] CH & ID SESSIONS 1. Infectious Disease Epidemiology (lecture) 2. Outbreaks (lecture + tutorial) 3. Immunization (lecture + tutorial) 4. Emerging Infectious Diseases (tutorial) u Assessment plan: — Mandatory tutorials (sign-in sheet) — Exam (MCQs) — Assignment (group work on EID) 2  REFERENCES Public Health Agency of Canada, Infectious Diseases section at https://www.canada.ca/en/public-health/services/infectious- diseases.html Canadian Immunization Guide. 6th edition. Ottawa. Health and Welfare. Canada, 2006 at http://www.phac-aspc.gc.ca/publicat/cig-gci/index- eng.php Provincial Communicable Disease Control Manual, http://www.health.gov.nl.ca/health/publichealth/cdc/health_pro_info.ht ml#disease Control of Communicable Diseases Manual. 20th edition, American Public Health Association, 2015 A virtual textbook: Primer on Population Health for Clinicians, AFMC - Ch.7, 11 https://phprimer.afmc.ca/en/ 3  KEY CONCEPTS FUNDAMENTALS OF EPIDEMIOLOGY ANALYTICAL FRAMEWORKS FOR COMMUNICABLE TOOLS FOR COMMUNICABLE DISEASE CONTROL DISEASE CONTROL A POPULATION PERSPECTIVE CDC Clinical ID Population-level perspective Individual perspective Prevent/reduce disease Treat patient transmission 5 KEY TERMS ¡ Infection vs. Infectious Disease Infection: Process of invasion of host by pathogenic agent Infectious Disease: Illness resulting from the infection ¡ Pathogenicity vs. Severity Pathogenicity: Ability of agent to infect & multiply (cause disease) Severity: Pathophysiological reaction of the host to infection 6 KEY TERMS ¡ Case: Person who presents a specific infectious disease. ¡ Asymptomatic case = Carrier: Person who harbors a specific infectious agent without discernible clinical disease. Carriers test positive but symptom negative: Ø Unapparent (Polio) Ø Convalescent (Salmonella) Ø Chronic (>1 year) (Hepatitis B) Ø § Public health measure: Isolation 7 KEY TERMS ¡ Contact: Person who has been exposed to an infectious disease ¡ May or may not have been infected ¡ May or may not develop disease and become contagious ¡ Public health measure: Quarantine 8  KEY TERMS ¡ Incubation period: Time between exposure and appearance of signs & symptoms ¡ Period of communicability = Infectious period: Time during which person is infectious Pertussis Disease Progression 9 KEY TERMS § Endemic vs Epidemic vs Pandemic Endemic: Occurrence of an infectious disease is constantly maintained in a region, without counting imported cases (continuous high prevalence) Epidemic: Occurrence of an infectious disease is increased in a population over a specific time (temporary high prevalence) Pandemic: Spread of an epidemic worldwide 10 ANALYTICAL FRAMEWORKS THE EPIDEMIOLOGIC TRIANGLE Agent Host Environment 12 AGENT Agent — Viruses — Bacteria Host Environment — Fungi — Parasites — Prions 13 HOST Agent Susceptibility of the individual host: — Natural defense mechanisms Host Environment — Genetics — Age — Health status — Living conditions — Shift from natural to “artificial” — Natural immunity vs Immunization — Active vs Passive immunity 14  HERD IMMUNITY — The resistance to the spread of an infectious disease within a population based on pre-existing immunity of a high proportion of individuals — Result of previous infection or vaccination — Requires — Immunity of high (but variable) proportion of group members and — Uniform distribution of immunes within group ENVIRONMENT Agent Vulnerability of a population: , — Living Conditions Host Environment — Water/Food — Plants/Animals — Climate — Pollution — Migration 16 INFECTIOUS DISEASE PROCESS (= CHAIN OF INFECTION) Agent Host Reservoir Portals of Portals of Entry exit Mode of Transmission 17 RESERVOIR = habitat in which the infectious agent normally thrives and multiplies. Agent — Human Host Reservoir (eg: chickenpox only in humans) Portals of Portals of Entry exit — Animal Mode of Transmission (eg: avian influenza in birds/ducks) — Natural environment (eg: Clostridium tetani in the soil) 18  TRANSMISSION OF RABIES Agent (lyssavirus) Reservoir Accidental Host (Human) (large carnivores & bats) Portals of Entry Portals of exit (breached skin/blood) (saliva) Mode of Transmission (bite) 19  TRANSMISSION Agent Mode of transmission: The means by which a Host Reservoir disease is spread from the reservoir to the host Portals of Entry Mode of Portals of exit Transmission Portal of exit: How the agent Portal of entry: How the agent leaves the reservoir enters the host u Contaminated water u Blood u Contaminated food u Digestive system u Secretions/Excretions (sputum, u Respiratory system feces, urine…) u Skin and Mucosa 20 MODE OF TRANSMISSION Direct transmission ¡ Immediate transfer to portal of entry – touching, biting, kissing, sexual intercourse ¡ Droplet spread to mucous membranes or conjunctiva (< 1 meter) 21 MODE OF TRANSMISSION Indirect transmission § Fomites: contaminated inanimate materials/objects (surgical instruments, dressings, kitchen utensils, linen…) § Bloodborne or vehicled by other bodily fluids/tissues and organs § Airborne § Water-borne § Food-borne § Vector borne (via parasites, mosquitoes…) 22 EG: RESPIRATORY ILLNESSES 23 TOOLS FOR COMMUNICABLE DISEASE CONTROL PUBLIC HEALTH TOOLS FOR CDC Inform Surveillance Prevent Vaccination programs Sanitation One Health Respond Case management Outbreak response SURVEILLANCE — Definition: Continuing scrutiny of all aspects of the occurrence and spread of a disease that are pertinent to effective control — Key examples: — Passive surveillance (mandatory physician & laboratory reporting) — Active surveillance (public health investigation) — Immunization (uptake & complications) — Environmental Monitoring (drinking water, air quality) 26 PHYSICIANS IN CLINICAL PRACTICE: WHAT ROLE IN CDC? o Surveillance: Mandatory notification of infectious diseases Voluntary sentinel surveillance o Control of disease: Treat the patient Prophylaxis for contacts o Prevention: Routine vaccination Advocacy & health education Source of information PRINCIPLES OF OUTBREAK MANAGEMENT UGME phase 2 Delphine Grynszpan, MD MPH FFPH [email protected] Definitions A cluster: Two or more cases related in time and geography Ø Infectious disease or not Ø Same source – or not An outbreak: Two or more related cases, increasing the incidence of the disease above the background rate Ø Infectious disease Ø Same source! Ø A localized epidemic Shigatoxigenic Escherichia coli (STEC): Chain of Infection 3 How the story begins… Over about one week at the end November 2017, Eastern Health CDC team received several reports of diarrheal illness from EHOs and clinicians… …then, the lab called in to report an increase in PCR positive results for STEC. What is going on? What do you do? Outbreak Investigation n Confirm the facts (Diagnosis? Outbreak?) n Agree a Case Definition n Analyze the data (Test the Hypothesis) n Control Measures (Immediate and then refined) n Communicate (Collaborators; Media/public) Iterative process: refine and confirm as investigation evolves Confirm the situation Is this an outbreak? – Confirm diagnosis = Are these true cases? Is there a defined disease or coherent syndrome? Is this a reporting/testing artifact? – Confirm relationship Are the cases related in time & space? Is it possible all cases were exposed to the same agent? – Compare with background rate Are there more cases than would be expected?  Case definition Time period under investigation Person – Clinical Criteria TIME Symptoms (self reported; medical examination) Lab results – Level of certainty PERSON Suspected (Person Under Investigation; Possible) Probable PLACE Confirmed Place of exposure – Refine definition towards likely exposure  Case definition: example… 10 individuals with: Range of symptoms including bloody diarrhea, diarrhea, vomiting, fever, abdominal cramps, malaise. Lab reports PCR positive for Shiga-toxin E Coli, of which 9 grew E Coli on culture. Onset of symptoms between November 18th to 26th Live in different communities in the Eastern Region, most in the metro area Eg: case definition Persons presenting with diarrheal illness, with onset on or after November 18th, 2017, living in Eastern region of NL. Confirmed: and with a positive, strain specific, culture of STEC Probable: and with a positive PCR result for STEC Suspected: only clinical symptoms Objectives of outbreak management Prevent Contain the transmission source Hypothesis The outbreak is due to this agent transmitted to persons through this source Likely agent? Mode(s) of transmission? Type(s) of exposure? Population at risk? Ø Guides the investigation Ø Iterative process Ø Justifies control measures Data collection Case questionnaires & diaries Contact tracing & testing Patients’ lab results Environmental sampling Data Analysis Descriptive: n Person/place/time/clinical n Epidemic curve Analytical: n Cohort study n Case-control study n Mapping: Geographic Information Systems n Genetics studies (whole genome sequencing) n Social networking study Epidemic curve Number of cases Case definition Confirmed or probable cases Time Preferably: date of onset (sometimes: lab results; official PH reporting…) Confirmed vs estimated data Sources of an outbreak & Epidemic Curves Point source Continuous Propagated Intermittent ON / OFF / Sources & Epidemic Curves --------------------------------- -----------------/--------------/------------ ----------------- ------------------- --------------/---------------------/--------------------- - -- ------- = incubation period Attack rates (Cohort study) Attack rate (%): nbr cases / total population exposed Calculated; on smaller populations/studies Eg: gastroenteritis at a party – 10 people attended (exposed) – 8 cases Exposure Nbr cases Attack rate cupcakes 8 80% sandwiches 5 50% salad 1 1% Nota Bene… Comparing disease transmissibility Secondary attack rate (2oAR or SAR): Percentage of contacts that develop disease (become cases) (usually calculated; small study) Reproduction number (R): Average number of secondary cases per case (based on modelling; large population) For person-person transmission! Depends upon the environment! What happened… US CDC also investigating a multi-state outbreak of a genetically related E Coli Epicurve of Canadian cases STEC incubation period: 1-10 days (median ≅3 days) Epicurve of US cases Source: PHAC, 2018 Control Measures n Control the source (Prevent new primary cases) n Prevent transmission (Prevent secondary cases) n Proportionate (balance harm vs benefit) n Reassess over time and review their effectiveness Control Measures n Prevent new primary cases – Limit exposure to possible source (voluntary/order) n Prevent secondary cases – Hygiene – Isolation/quarantine – Prophylactic medication where indicated – Immunization – Treatment of cases (beware asymptomatic carriers) What immediate control measures do you recommend? 8/10 cases report eating a Caesar salad from a major retailer in the preceding week A. Hygiene advice? B. Isolate those who are ill? C. Recall the salads? D. Close the retailer? E. Ask the families to destroy remaining food? Communication — Informing affected individuals — Informing health community (surveillance/management) — Authorities — Informing businesses and services involved — General public & Media When is an outbreak over? Host – Agent – Environment… No new cases? Source contained? Transmission interrupted? Time No new cases in twice the incubation period Source investigation of Canadian cases Source: CNPHI, 2018 Retrospective cohort study to investigate source producer/brand Product sampling Product tracing