Vaccine preventable diseases 13-16

Question 1

Describe the global burden of mortality and morbidity attributable to vaccine preventable disease

Answer 1

Vaccines are an effective intervention to decrease morbidity and mortality due to the infection in under 5’s.
It is dependent on several factors and only effective if given:
- Immunological factors
Politics, peace and resources
Environmental factors

Question 2

What is the definition of a vaccine?

Answer 2

An antigenic substance prepared from the causative agent of a disease or a synthetic substitute, used to provide immunity against one or several diseases

Question 3

Describe the progression of infant immunity and how this affects risk of infection

Answer 3

Infants are born with passive immunity from the mother but immunological maturation increases significantly after 1 year
- Th2 cells prevalent initially with IL-4 + IL-10 as not to reject mother and baby
- Th1 cells prevalent after 1 year –> babies won’t respond well to vaccines
Pragmatically vaccine infants younger than 1 years old as mother will be more likely to attend hospital due to maternal leave.

Question 4

Give 4 examples of diseases affected by global health factors

Answer 4

1) Measles - virus which causes a rash due to Vit A deficiency. In areas of conflict and rural areas there is 0 coverage which then spreads to refugee camps. Increased coverage in India but decrease in S Sudan and Syria due to lack of infrastructure and government instability
2) Tetanus - toxin mediated by Clostridium tetani. Increased prevalence in areas w/ high risk birthing practices e.g. using animal faces to cover placental cord; many countries offer tetanus vaccine but not in the UK as high neonatal mortality
3) Pertussis - whooping cough; high risk in neonatal period –> neonatal apnoea
4) Haemophilus Influenza B - Very effective vaccine but takes 9-11 years to introduce into LICs vs HICs
5) Poliomyelitis - reported in Yemen and S Sudan due to not maintaining coverage

Question 5

What are the characteristics that a vaccine preventable disease must have?

Answer 5

• Known causative agent
• Not hyper-variable/stable agent
• Antigens that are different to humans
• Known mechanism of infection/disease
• Antigen must induce stable/long last immunity

Question 6

What are the characteristics that a vaccine preventable disease should have?

Answer 6

• Minimal reservoir/host range
• Natural immunity protects
• Acute not chronic infection
• Culturable causative agent
• Animal agent

Question 7

What are the characteristics of an ideal vaccine?

Answer 7

Completely safe
East to administer
Single dose, needle-free
Cheap
Stable
Active against all variants
Life-long protections

Question 8

What are the characteristics of an eradicable infectious disease?

Answer 8

Safe + effective vaccine
Genetically stable target
No animal reservoir
Eliminates persistent infection, or persistently infected host can't transmit
Easy and reliable diagnostics

Question 9

What causes variability in vaccine efficacy? (x2)

Answer 9

Host factors

Vaccine characteristics

Question 10

What are the host factors that cause variability in vaccine efficacy?

Answer 10

Age
Co-morbidity: including frailty/function
Prior exposure
Time since vaccination
Underpinning infection
Maternal immunisation

Question 11

What are the vaccine characteristics that cause variability in vaccine efficacy?

Answer 11

Mode of delivery
Live-vs inactivated
Vaccine composition
Addition of adjuvant
Match to circulating strains

Question 12

What causes variability in global vaccine efficacy?

Answer 12

Differences in host genetics
Circulating strain differences
Underpinning infections
Vaccine batches
Logistics

Question 13

What is herd immunity?

Answer 13

A form of indirect protection from infectious disease that occurs when a large % of a population has become immune to an infection, thereby providing a measure of protection for individuals who are not immune.

Question 14

What is the definition of R0?

Answer 14

Basic reproduction number = the number of cases one case generates on average over the course of their infectious period

Question 15

What is the definition of R1?

Answer 15

Effective reproduction number = a population will rarely be totally susceptible to an infection in the real world; reflects the number of susceptible cases

Question 16

What is herd immunity threshold?

Answer 16

(Pc) The proportion of individuals that need to be vaccinated to control the incidence of infectious disease. This increases as R0 increases.

Question 17

Why is herd immunity important in vaccine preventable diseases?

Answer 17

By vaccinating children for example, you protect against infants and the elderly who may be immunocompromised. It is also important to carry out targeted vaccination.

Question 18

What is targeted vaccination?

Answer 18

Targeting groups of people who have an increased risk of transmitting a disease. Risk of spread can vary with behaviour e.g. STI/partner number, sex - if you vaccinate these people, you can get elimination for a lower overall vaccination rate e.g. HPV.
Age is a key determinant - can reduce proportion vaccinated.

Question 19

What are the 5 different types of vaccines?

Answer 19

(CRIDL)
Conjugate vaccines
Recombinant protein vaccines
Inactivated toxoid vaccines
Dead pathogen
Live, attenuated vaccine

Question 20

What is the MOA and example of conjugate vaccine?

Answer 20

1) Polysaccharide coat component is coupled to an immunogenic ‘carrier’ protein
2) Protein enlists CD4 help to boost B cell response to the polysaccharide

E.g. Streptococcus pneumoniae

Question 21

What is the MOA and example of a recombinant protein vaccine?

Answer 21

1) Induces classic neutralising antibodies

E.g. Hep B Surface Antigen (HbSAg)

Question 22

What is the MOA and example of an inactivated toxoid vaccine?

Answer 22

1) Chemically inactivated form of toxin e.g. tetanus toxoid
2) Induces antibody
3) Antibody blocks the toxin from binding the nerves

E.g. Tetanus toxoid

Question 23

What is the MOA and example of a dead pathogen vaccine?

Answer 23

1) Pathogen chemically killed
2) Induces antibody and T Cell responses

Eg. influenza split vaccines

Question 24

What is the MOA and example of a live attenuated vaccine?

Answer 24

1) Pathogen attenuated by serial passage which leads to loss of virulence factors
2) Replicate in situ which triggers innate response + boosts the immune response

E.g. BCG

Question 25

Give examples of 5 potentially preventable diseases?

Answer 25

``` SARS MRSA Dengue HIV Malaria TB ```

Question 26

What are the challenges to vaccine development?

Answer 26

Wrong type of protection High pathogen variation - strain replacement e.g. Influenza Natural infection is not protective - Cryptic antigens; evasion from immune response e.g. malaria Vaccine induced disease Flawed translation from animal models Vaccinating people with poor immune response (heterogeneity) i.e. not applicable to whole population

Question 27

What are the socio-economic barriers of developing new vaccines?

Answer 27

``` Injection safety Logistics/cold chain Development issues: time, cost of vaccine development is high, cost of the product Weak public health systems Public expectation of risk-free vaccines ```

Question 28

What are the concerns of sub-population about vaccines and vaccine programmes?

Answer 28

Complex + context-specific --> varies across time, place and vaccines 3 C's model of vaccine hesitancy: Complacency = Lack of perceived need/ value for vaccine Convenience = access to vaccine Confidence = level of trust in vaccine, provider or process SAGE working group determinants of vaccine hesitancy: contextual influences, individual/social influences/vaccine and vaccination-specific issues

Question 29

What is the WHO definition of vaccine hesitancy?

Answer 29

Delay in acceptance or refusal of vaccines despite availability of vaccination services

Question 30

What is the vaccine hesitancy continuum?

Answer 30

``` Unquestioning acceptance Accept cautiously Hesitant Delay some vaccines Refuse all vaccines ```

Question 31

What is the psychometric paradigm?

Answer 31

The public tend to judge risks not by fatalities but by the characteristics of risk

Question 32

Describe the HPV vaccine case in Denmark.

Answer 32

In 2012, a number of cases of postural Orthostatic tachycardia syndrome (POTS) and similar syndromes in young women were reported + was hypothesised that it was linked to the HPV vaccine that was started in 2008/9. A TV documentary was subsequently made and this dramatically decreased HPV coverage across the country due to social media as well. Coverage dropped from 80-90% to 20-30%. In 2015, the European Medicines Agency (EMA) reviewed the literature and found no evidence for a causal association. Later studies showed that the girls reporting those syndromes were more frequent healthcare users so factors other than the vaccine probably caused it. Coverage slowly increased from 27% in June 2016 to 73% in June 2018 (Lynge et al., 2018). But unfortunate that those girls could have been vaccinated when they were sexually naive as they would have been 15-16 where one third of them would have already by sexually active.

Question 33

Describe the HPV Vaccine case study in Japan.

Answer 33

In 2013 an adverse event following immunisation claim was released causing a dramatic drop in vaccine uptake in Japan. A preliminary + allegedly fraudulent mouse study showed that the vaccine caused brain damage and was spread by the media + unconfirmed video reports of girls in wheelchairs and having seizures after getting immunised. Anti-vaccine groups also blamed the vaccine for causing chronic pain + heart + neuro issues. Government then suspended any proactive recommendations for the HPV vaccine despite finding no evidence to support claims - demonstrates impact of governments. Turned out the brain that was being shown on TV wasn't even the mouse brain that was injected with the HPV vaccine. The mice used were genetically modified to produce auto-antibodies naturally during aging. Serum full of these antibodies was taken from the mice and sprayed on brain sections of normal mice and photographed to show brain damage. Vaccine coverage has decreased dramatically from 70% (2013) to less than 1% (2017).

Question 34

What are the interventions shown to increase vaccination in healthcare providers?

Answer 34

Free vaccine Easy access Educational activities, reminders or incentives Opt outs or mandatory immunisation policies Peer vaccination People turn to GP and pharmacies most so more likely to vaccinate if healthcare providers recommends it.

Question 35

What is an AEFI?

Answer 35

Adverse Event Following Immunisation Healthcare workers need to be well trained to address serious AEFI's: investigation, causality assessment, communication Effective system for monitoring safety of vaccines; safety signals need to be well investigated and responded to. When AEFIs are well handled the risk of vaccine hesitancy is minimised.

Question 36

What are the 3 things to address vaccine hesitancy?

Answer 36

Identify susceptible population groups Diagnose drivers + barriers to immunisation Design and evaluate evidence-based interventions