Slide 1: Immunization

Slide 2: History

• Mims C et al. Medical Microbiology. 2004.

Slide 3: Terms

• Immunization - conferring immunity by artificial means
• Vaccination - conferring immunity to a disease using a vaccine or special antigenic material to stimulate the formation of appropriate antibodies
• Vaccine - preparation of antigenic material; stimulates Ab production; confers active immunity vs. disease
• Latin "vacca" = cow (from cowpox)

Slide 4: Immunization

• Using vaccines or antibody-containing preparations to provide immune protection vs. specific diseases
• Passive - individual acquires immunity through the transfer of antibodies formed by an immune individual or animal (preformed antibodies from another host; protects individual exposed to disease)
• Active (vaccines) - administration of a vaccine so that the patient actively mounts a protective immune response (modified/purified pathogens or their products; stimulate host to produce own specific immunity)

Slide 5: Active Immunization - Attenuated (Live) Vaccines

• Use pathogens that have reduced virulence
• Can result in mild infections but no serious disease
• Contain active microbes that stimulate a strong immune response due to the large number of antigen molecules
• Can provide contact immunity through vaccinated individuals infecting those around them
• Can be hazardous because modified microbes may retain enough residual virulence to cause disease

Slide 6: Live Attenuated Pathogens

• Multiplies inside human host & provides strong antigenic stimulation
• Provides prolonged immunity (years to life), often with single dose
• Vaccine often provides cell-mediated immunity
• Disadvantage: can revert to virulent form
• Do NOT give to immunocompromised or pregnant patients

Slide 7: Live Attenuated Vaccine - Advantages vs Disadvantages

• Act like the natural infection with regard to immune response
• Stimulates longer lasting antibody production
• Induce a good cell-mediated response
• Induce antibody production and resistance at the portal of entry for the natural virus
• Strong immune response means fewer doses needed; boosters usually not required

• Must be kept cold (cold chain challenges in remote communities)
• Cannot be given to immunocompromised people (risk of serious illness)
• Small risk of reversion to a more virulent strain (genetic mutation in the weakened germ)

Slide 8: Examples of Diseases for which Live Attenuated Vaccines are Used

• Measles, Mumps, Rubella (MMR combined vaccine)
• Rotavirus
• Smallpox
• Chickenpox
• Yellow fever

Slide 9: Precautions and Contraindications to Live Vaccination

• People with impaired immunity / taking immunosuppressant medications
• Pregnant women

Slide 10: Active Immunization - Inactivated (Killed) Vaccines

• Whole agent vaccines - produced with deactivated but whole microbes
• Subunit vaccines - produced with antigenic fragments of microbes
• Both types are safer than live vaccines (cannot replicate or mutate to virulent form)
• Antigenically weak because microbes don't reproduce (fewer antigenic molecules)
• Often contain adjuvants - chemicals added to increase effective antigenicity

Slide 11: Inactivated Vaccines

• Cannot replicate
• Generally not as effective as live vaccines
• Less interference from circulating antibody than live vaccines
• Generally require 3-5 doses
• Immune response mostly humoral
• Antibody titer may diminish with time

Slide 12: Killed Micro-organism

• Does not multiply in human host
• Immune response depends on Ag content of vaccine
• Multiple doses required with subsequent booster doses
• Provides little cell-mediated immunity
• No possibility of a vaccine-associated infection

Slide 13: How to Get Inactivated Vaccines

• Use of formalin
• Heat
• Irradiation

Slide 14: Inactivated Vaccine - Advantages vs Disadvantages

• No risk of reverting to virulent form
• Can be given to immunocompromised persons
• Easier to transport and store (can be freeze-dried)

• Extreme care required to ensure all organisms are inactivated
• Need very large quantities of organism to create the vaccine
• Can be costly to inactivate some germs/components
• Immunity is often brief and must be boosted
• Local IgA at the site of entry is not induced adequately by systemic administration
• Cell-mediated response is often poor

Slide 15: Examples of Diseases for which Inactivated Vaccines are Used

• Flu, Polio, Hepatitis A, Hepatitis B, Diphtheria, Tetanus, Meningococcal disease, Pneumococcal disease, Hib disease (Haemophilus influenzae type b), Pertussis, Rabies

Slide 16: Precautions and Contraindications to BOTH Live and Inactivated Vaccines

• People with major illness or fever >38.5°C should postpone until recovered
• Some vaccines (yellow fever, rabies, flu) may contain egg albumin - allergy caution
• People with a previous anaphylactic reaction to a vaccine/component SHOULD NOT receive that vaccine

Slide 17: Active - Microbial Extracts

• Extracted molecules (Ags): from pathogen, from acellular filtrate of culture medium, or via recombinant DNA techniques
• Vaccines can be prepared with toxoids (derivatives of exotoxins)
• Used when pathogenicity is due to secreted toxin (e.g., tetanus, diphtheria)

Slide 18: Active - Conjugated Vaccines

• Covalent binding (conjugation) of an antigenic polysaccharide to a protein - produces higher Ab titres than unconjugated polysaccharide
• Especially important in children <2 years
• Examples: Hib conjugate (polysaccharide conjugated to diphtheria toxoid protein), Meningococcal type C polysaccharide conjugate

Slide 19: Active - Toxoids

• Derivatives of bacterial exotoxins
• Rendered non-toxic but remain immunogenic
• Administration: IM, SC
• Examples: Tetanus, Diphtheria

Slide 20: Active Immunization - Toxoid Vaccines

• Chemically or thermally modified toxins to stimulate active immunity
• Useful for some bacterial diseases
• Stimulate antibody-mediated immunity
• Require multiple doses (few antigenic determinants)

Slide 21: Active Immunization - Vaccine Safety

• Mild toxicity most common (pain at injection site, general malaise, fever that can rarely induce seizures)
• Risk of anaphylactic shock
• Residual virulence from attenuated viruses
• Allegations that certain childhood vaccines cause/trigger autism, diabetes, asthma - research has not substantiated these allegations

Slide 22: Passive Immunization

• IgG - immediate protection - no memory
• Standard Igs (human, animals) - non-specific; pooled plasma from donors; Igs vs. many common viruses
• Human hyperimmune serum (high titre) - specific; from donor with high titre Abs to specific virus; against a single specific virus

Slide 23: Passive Immunity

• Transfer of antibody produced by one human or animal to another
• Temporary protection
• Transplacental transfer is the most important source in infancy

Slide 24: Sources of Passive Immunity

• Almost all blood or blood products
• Homologous pooled human antibody (immune globulin)
• Homologous human hyperimmune globulin
• Heterologous hyperimmune serum (antitoxin)

Slide 25: Age & Immunity

• Passive immunity from mother: Maternal IgG crosses the placenta; before and at birth IgG present; breast milk provides secretory Abs (GI & resp. tract)
• Active Immunization: Infant begins to produce Abs in 1st year; start immunization at 2 months (usually)
• Elderly have a weaker immune response

Slide 26: Risks of Immunisation

• Side effects on any part of vaccine: redness, induration, ache, fever, crying, allergy
• Immunisation = small regulated infection: mild reaction, not target tissue infection
• Not real expectances

Slide 27: Main Causes of Reactions to Vaccination

• Personal characteristics of the vaccine recipient
• Problems with the vaccine itself
• Problems with doing the vaccination

Slide 28: Problems with Vaccines

• Localized reactions at site of injection
• Anaphylaxis to Ag or non-microbial vaccine content (eggs)
• Contamination with pathogen
• Reversion of attenuation
• Lack of efficacy if another concurrent infection (rubella & polio vaccine)
• Organisms with many serotypes

Slide 29: Success of Immunization Program

• Composition of vaccine
• Life-long immunity
• Administration (timing, site, conditions)

Slide 30: Immunization Schedule - When?

Slide 31: Key Definitions

• Herd Immunity - High levels of immunization in one population which leads to protection of an unvaccinated population
• Cocoon Immunization - Immunization of those in close contact to someone who cannot be vaccinated
• Toxoid - A toxin produced by a bacterial organism that is inactivated by formalin

Slide 32: Exposure to Antigen

• Primary exposure: IgM antibodies predominate initially; IgG rises days after the initial response; blood concentrations become comparable after several days
• Subsequent exposures: IgM and IgG start to increase at about the same time; IgG concentrations are considerably higher than IgM after several days

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Types of Public Health Surveillance

1. Passive Surveillance

• Health authorities receive reports voluntarily submitted by healthcare providers, laboratories, and hospitals in accordance with regulations
• Simple and inexpensive; can cover large populations
• Main limitation: underreporting, delays, and variable data quality - the denominator (total encounters) is unknown
• Examples: notifiable disease reporting, death certificates, pharmacy dispensing data

2. Active Surveillance

• Public health authorities proactively contact health providers, labs, or community members to seek out cases
• Produces more complete, accurate data with a known denominator (allows calculation of true incidence/prevalence)
• More resource-intensive than passive surveillance
• Examples: contact tracing during outbreaks (Ebola, STIs), house-to-house searches, weekly phone calls to clinics for influenza case counts

3. Sentinel Surveillance

• A selected sample of reporting sites (specific clinics, hospitals, or laboratories) is designated to represent a geographic area or population
• Can be active or passive
• Goal is to estimate magnitude and trends of a disease, not to detect every case
• Best for common diseases (influenza, diarrheal illness)
• Less effective for localized epidemics requiring early detection (e.g., hemorrhagic fevers)
• Example: WHO global influenza sentinel surveillance network

4. Syndromic Surveillance

• Monitors symptoms and syndromes (rather than confirmed diagnoses) to detect emerging health threats before laboratory confirmation
• Data sources: ED chief complaints, pharmacy sales (e.g., OTC antidiarrhoeals), school/workplace absenteeism, ambulance call logs, social media
• Allows earlier detection and faster public health response
• Limitation: high false-positive rate; low specificity
• Example: influenza-like illness (ILI) monitoring; post-9/11 bioterrorism detection systems (BioWatch)

5. Laboratory-Based Surveillance

• Uses lab techniques (genomic sequencing, serology, culture, PCR) to identify and characterize pathogens
• Highly accurate for identifying causative organisms and tracking strain evolution (e.g., antimicrobial resistance, viral variants)
• Requires adequate lab infrastructure
• Example: SARS-CoV-2 genomic surveillance for variant detection

6. Indicator-Based Surveillance (IBS)

• Gathers data on specific, pre-defined indicators (case counts, hospitalisations, mortality rates) from structured formal sources (registries, reports)
• Good for tracking known diseases over time
• Less effective at identifying novel or unexpected health threats

7. Event-Based Surveillance (EBS)

• Collects unstructured reports from informal sources - media reports, social networks, community informants, NGO bulletins - as well as formal sources
• Rapid detection of unusual health events, including novel diseases
• Data quality is variable; requires verification before action
• Example: ProMED-mail, WHO event management system (EMS)

8. Notifiable Disease Surveillance

• A legally mandated form of passive surveillance where certain diseases must be reported to authorities
• Forms the backbone of most national surveillance systems
• Examples: tuberculosis, measles, cholera, hepatitis, foodborne illness outbreaks

Summary Table