Vaccinology - Vaccination in practice Flashcards
What is the most important opportunity to lower the incidence of tropical diseases?
Improved education & hygiene
What is the causative agent of diphtheria?
Corynebacterium diphtheriae
What causes symptoms in diphtheria?
Diphtheria toxin
What are the symptoms of diphtheria? (6)
- Fever
- Swollen neck due to lymphadenopathy
- Dyspnoea due to swelling of the nasopharynx
- Cutaneous laesions
- Cardiac involvement
- Neurologica/muscle involvement (late stage)
How many % of diphtheria patients have cardiac involvement?
10-20%
How many % of children worldwide have been vaccinated against diphtheria?
90%
How many children remain unvaccinated for diphtheria? Where are they primarily located?
~20 million, mostly in Africa
What is the WHO goal regarding diphtheria vaccination?
Making immunization available to everyone by 2030
What are the challenges to increasing global vaccination coverage in low- and middle income countries (LMICs)? (7)
- Financial: lack of public funding
- Economic: low commercial viability -> vaccine shortages
- Logistical: cold chain
- Attitudes towards vaccines
- Political: conflict
- Other health-related problems
- Vaccine safety issues (immune-enhancement of disease, live vaccines)
What are health-related reasons that prevent good vaccination coverage in low- and middle income countries (LMICs)? (3)
- AIDS
- Malnutrition
- AIDS
What are the challenges to increasing global vaccination coverage in high-income countries (HICs)? (7)
- Financial: budget travel
- Economic: low commercial viability -> shortages
- Logistical: lack of planning
- Attitudes: antivaxx
- Political: lack of insurance coverage
- Health: ageing
- Vaccine safety (immune-mediated enhancement of disease, live vaccines)
Why is budget travel a problem for good vaccine coverage in high-income countries (HICs)?
Budget travellers don’t spend money on vaccinations to protect themselves against disease
How was hepatitis A eradicated in high-income countries (HICs)?
Improving hygiene
What are the symptoms of hepatitis A? (6)
- Juandice
- Dark urine/pale stools
- Diarrhoea
- Nausea
- Vomiting
- Abdominal pain
How many % of children have no symptoms during a hepatitis A infection?
80-95%
What is the mortality of hepatitis A in adults?
2,1%
What is the transmission route of hepatitis A?
Faecal-oral transmission through direct contact or food/water
What are the predictors of hepatis A infection? (3)
- Socio-economic status
- Household size
- Access to sanitation facilities
What is the adherence to vaccination guidelines of travellers?
~60%
There [is/isn’t] a hepatitis A vaccine available
There is
How many vaccine doses are required for hepatitis A? How long is the protection?
2 doses = 40 years protection
What determines the acceptable failure rate of vaccines? What is generally considered acceptable?
Acceptable failure rate depends on the pathogen
Generally 10-15%
What is the standard course of action upon vaccine failure?
Repeat vaccination schedule
To which virus family does yellow fever belong?
Flavivirus
How is yellow fever transmitted?
Aedes & Haemogogus mosquitos
How many % of yellow fever-infected individuals are symptomatic?
13-15%
What are the symptoms of yellow fever?
- Red eyes
- Headache
- Jaundice
- Muscle ache
- Hepatomegaly
- Vomiting
- Back pain
- Haemorrhage
How many % of symptomatic yellow fever-infected individuals become haemorrhagic?
25%
How many % of haemorrhagic yellow fever patients die?
50%
What are the laboratory characteritics of yellow fever? (3)
- High CRP
- High transaminases (ALAT/ASAT)
- Low thrombocytes
What is the treatment for symptomatic yellow fever?
Only symptomatic treatment available, no antivirals
What is the global incidence & mortality of yellow fever?
Incidence: 200.000/year
Mortality: 30.000/year
Where do yellow fever cases primarily occur?
Around the equator in Africa & Asia
What is the reservoir of yellow fever?
Non-human primates
Can yellow fever be eradicated?
No -> the animal reservoir makes it impossible to eradicate this disease (with current technology)
What are the possible transmission cycles of yellow fever? (3)
- Jungle
- Intermediate / savannah
- Urban
What is the jungle transmission cycle of yellow fever?
Passed between non-human primates by mosquitos, incidental infection of humans
What is the intermediate / savannah transmission cycle of yellow fever?
Hybrid transmission cycle, mosquitos pass the virus between humans & non-human primates
What is the urban transmission cycle of yellow fever?
Passed between humans by mosquitos
True or false: yellow fever can be transmitted from person-to-person
True, but: humans are very poor at transmitting yellow fever without mosquito vectors
There [is/isn’t] a vaccine available for yellow fever
There is a good vaccine available
How many doses of yellow fever vaccine are needed to protect an individual? How long does this protection last?
One dose = life-long protection
What are the main problems of the yellow fever vaccine? (3)
- Shortages
- Live attenuated vaccine cannot be given to immunocompromised individuals, infants & elderly
- Rare vaccine complciations
Who are the producer of the yellow fever vaccine?
Sanofi Pasteur
What is the yearly available stock of yellow fever vaccine? How many doses are needed?
80 million available, 400 million needed
What are the rare vaccine complications of yellow fever? (2)
- YEL-AND = neurological disease
- YEL-AVD = visceral disease
What are the benefits of the live-attenuated yellow fever vaccine? (2)
- Induces long-lived memory responses
- Induces effective CD8+ effector and memory subsets
What enables the live attenuated yellow fever vaccine to induce long-lived memory responses and CD8+ responses?
- Live attenuated vaccine spreads systemically -> induces a thorough immune response
- Live attenuated vaccine gives a longer antigen exposure -> enough time to develop a T-effector memory subset
Which cells are mainly responsible for protection against yellow fever post-vaccination?
T-effector memory cells
Why is a subunit vaccine not useful for yellow fever?
Does not induce the CD8+ T-cell memory subset necessary to defend against the virus
What is the WHO goal regarding yellow fever?
Eliminate outbreaks by 2026
How many % population immunity is required to prevent yellow fever outbreaks?
60-80%
To which virus family does dengue belong?
Flavivirus
How many serotypes of dengue virus are there?
4
What is the mode of transmission of dengue virus?
Aedes mosquitos
What are the symptoms of mild dengue? (3)
- Rash
- Fever
- Muscle/joint pain
What is the devere form of a dengue infection?
Dengue heamorrhagic fever syndrome
Why are secondary, heterotypic dengue infections problematic?
They allow for antibody-dependent enhancement (ADE) of disease
What is a ‘heterotypic infection’? (definition)
Infection by a different serotype of a virus you have previously been infected by
What is the danger of dengue vaccines?
Can cause antibody-dependent enhancement (ADE) disease enhancement if the vaccine serotype differs from the infection serotype
What is the effect of dengue vaccination of individuals that were seropositive for dengue prior to vaccination?
90% risk reduction by vaccine
What is the effect of dengue vaccination of individuals that were seronegative for dengue prior to vaccination?
Protection for some times (~7 months), but 2x higher risk of symptomatic dengue after this period
What is the effect of vaccine-induced ADE of dengue on global vaccine confidence?
A vaccination campaign in the Philippines greatly reduced global vaccine trust
What is the mechanism of antibody-dependent enhancement (ADE) in dengue?
Antibodies against one serotype bind to other serotypes, but don’t neutralize the virus. The antibodies then form an entry point into macrophages due to Fc-mediated phagocytosis -> viral replication within the macrophage
What is the solution to vaccine-induced antibody-dependent enhancement (ADE) in dengue?
Develop a vaccine that produces serotype-specific antibodies for all 4 serotpyes
What is an important requirement of dengue vaccines aimed at preventing antibody-dependent enhancement of disease?
The serotype-specific antibodies really need to be unable to bind to other serotypes, to prevent forming an entry point into macrophages
What is the most serotype-specific gene of dengue viruses? What is a downside of aiming for this gene?
Domain III of the envelope (E-)protein
Downside: not very immunogenic -> lot of adjuvants required
What is the aim of the BCG vaccine?
Prevent miliary TB & TB meningitis (but not infection)
What is the difficulty of evidence-based vaccination immunocompromised individuals?
Limited studies & heterogeneous population -> often no good evidence-based practices established
Which strategy is often taken in the vaccination of immunocompromised individuals when there is no evidence-based strategy?
Eminence-based -> advice based on reasoning
Vaccinations [are/are not] indicated in immunocompromised individuals
Immunocompromised individuals greatly benefit from any vaccine to boost & support their weak immune system. Caveat: no live attenuated vaccines
Which type of vaccines is always contra-indicated in immunocompromised individuals?
Live (attenuated) vaccines
What is a risk of vaccination of immunocompromised individuals?
It may in some instances lead to worsening of underlying disease
Into which rough groups can immunocompromised individuals be grouped? (4)
- Compromised barrier function
- Primary immunodeficiencies
- Los of humoral immunity, not-being PID
- Loss of cellular immunity, not-being PID
What are examples of instances of compromised barrier function that can lead to a weakened immune defence? (3)
- Use of antacids
- IBD
- Severe skin disease
What are the consequences for vaccination of immunocompromised individuals due to compromised barrier function?
Relatively normal immunity -> can receive normal vaccinatinos
Addition advice: vaccination for Salmonella typhi when travelling to the tropics
Which precaution should individuals with a compromised barrier function take before travelling to the tropics?
Salmonella typhi vaccine
For which type of infections are individuals with a compromised barrier function especially susceptible?
GI-infections
What is the advice regarding vaccination of individuals with severe primary B-lymphocyte disorders?
No live vaccines
What are examples of severe primary B-lymphocyte disorders? (2)
- XLA
- T-B- SCID
What is the advice regarding vaccination of individuals with less-devere primary IgA/IgG deficiencies?
No oral polio vaccine & varicella zoster vaccine, other vaccines are safe
What is the advice regarding vaccination of individuals with primary T-lymphocyte disorders?
No live vaccines
What is the downside of vaccination of individuals with primary T-lymphocyte disorders?
Vaccine efficacy of all vaccines severely reduced
What is the advice regarding vaccination of individuals with primary complement disorders?
All vaccines are safe and strongly recommended to boost weakened immune system. Sometimes extra vaccines given.
Which type of vaccine is especially recommended for individuals with primary complement disorders?
Polysaccharide vaccines
What is the advice regarding vaccination of individuals with primary phagocytosis disorders?
No live bacterial vaccines, live-attenuated vaccines probably safe. All vaccines effective.
What is the advice regadering vaccination of individuals with acquired loss of humoral immunity? (2)
- Follow the same rules as for primary B-cell disorders -> no live vaccines
- Check antibody titres post vaccination
What are causes of acquired loss of humoral immunity? (3)
- B-cell or antibody-depleting therapies
- Loss of antibodies due to nephrotic syndrome or other causes
What is the advice regadering vaccination of individuals with acquired loss of cellular immunity? (3)
- Follow the same rules as for primary T-cell disorders -> no live vaccines
- Give additional vaccines prior to/during therapy: VZV & pneumococcal
- Check titres post-vaccination
What are causes of acquired loss of cellular immunity? (3)
- T-cell depleting therapies
- Malignancy
- HIV
When does corticosteroid treatment count as mild immunosuppression?
<30 mg prednisone/day (or equivalent)
When does corticosteroid treatment count as severe immunosuppression?
> 30 mg prednisone/day (or equivalent) for >14 days
How long can the effect of severe immunosuppression by corticosteroids last?
Up to 3 months
What determines the duration of recovery after severe immunosuppression by corticosteroids?
Higher dose/longer duration = longer recovery
What is are the prednisone equivalents of 10 mg prednisone of 1. hydrocortisone, 2. methylprednisolone, 3. triamcinolone, 4. dexamethasone
10 mg prednisone =
1. 40 mg hydrocortisone (x4)
2. 8 mg methylprednisolone (x0,8 OR /1.25)
3. 8 mg triamcinolone (x0,8 OR /1.25)
4. 1,5 mg dexamethasone (x0,15 OR /6.66)
