Benefits of Vaccination on both an individual and a population level?
Individual Level:
- immunity to infection
Population level:
- Reduced transmission of infection
- reduced disease in vaccinated AND unvaccinated people=HERD IMMUNITY!
THe first disease modified substantially by vaccination was….
Small Pox
Used to kill ~10% of population during epidemics.
Shared similar epitopes with ‘Cow-pox’, which was noticed by Edward Jenner. This is easy to produce, stable and relatively cheap, and was the first world-wide vaccination scheme.
How do vaccinations actually work
They allow us to produce immunity against protein antigens, usually by injecting antigens
- Protein Antigens → stimulation of T-cell dependent antibodies
- so you have relatively high circulating concentrations that will hopefully neutralise disease , and producing immunological memory for fast response
- Polysaccharide antigens→ stimulation of T-cell independent antibodies
- not strong or long-lasting response, not very good
- Live viral vaccines → stimulation of antibodies, CD8 cytotoxic cells
- a much broader range of immunity
Difference between a ‘live attenuated’ and an ‘inactivated’ vaccine?
Live Attenuated:
- live virus or live bacteria
- but NOT pathogenic
Inactivated Virus:
- Whole viruses or bacteria (old technique, chemically inactivated) or fractions (newer method)
- protein-based vaccines
- toxoids (inactivated bacterial toxin), subunit or subvirion
- Polysaccharide-based vaccines
- pure cell-wall polysaccharide from bacteria, not effective
- Conjugate polysaccharide vaccines
- cell-wall polysaccharide chemically linked to a protein
- much better and longer lasting
what are ‘live’ vaccines and sshould we be worried about them being potentially pathogenic?
- Lab-modified virus or bacteria
- Replicate and produce immunity but not illness
- Generally lifelong immunity
Viral: measles, mumps, rubella, varicella, oral polio vaccine
Bacterial: BCG (tuberculosis, with some but not 100% immunity), oral typhoid
Reassorted: Rotavirus vaccine (Rotateq
What’s the issue with Reassorted vaccines such as the rotavirus (Rotateq)?
- enginered antigen genes into differenct capsules, so you’ve got losts of different epitopes being responded to.
- So although they have effective, long-lasting immunity, they’re going through an infectious cycle
- This can cause danger in immunocompromised or immunodeficient people!
What are inactivated Vaccines?
Killed antigen Vaccines
- NOT lifelong immunity with one dose, no capacity to replicate
- repeat immunisation neccessary (to build sufficient antibodies)
Whole Viral: Influenza, injected polio, rabies and hepA
Whole Bacterial: Pertussism typhoid, cholera
“Fractional” vaccines: more common nowadays
- Subunits (hep B, influenza, acellular pertussis)
- ‘Toxoids’ (diphtheria, tetanus) anitgens derived from toxins that have been purifed and chemically changed so they lose their toxicity whilst maintaining their shape!
Describe this picture
Whole Love organism Vaccine: one dose of infectious agent (that grows and replicates) produces a period of exposure to the immune system, optimally mirroring the infectious process of the thing you’re trying to protect against. Lots of antibody production, lots of memory and cytotoxic cells, and long-lasting immunity
Killed organism/componenets of an organism: single shot (just the antigen with no ability to replicate), limited IS response, so to build up enough anitbodies and memory, you need to give 3-4 or more doses
What are the two important Recombinant Vaccines to know
- Hepatitis B vaccine: fractionated, produced by recombinately making antigens in a yeast vector and then purifying antigens from those.
- Live Attenuated influenza Vaccine (LAIV): enhineered to replicate effectively in the mucosa of the nasopharynx but not in lungs
- ideal infectious profile to stimulate Immune system, but not a pathogenic profile
Some fractional vaccines are given _______, But attenuated live vaccines are given at the ages _________. Why is this?
Some fractional vaccines are given at 6wks, 3mths and 5mths with booster, But attenuated live vaccines (MMR: measles, mumps, rubella) are given at the ages post 15mths.
We wait 15mths to be certian that the child is not immunocompromised, as these could then be potentially pathogenic.
The earlier vaccines are safe because they are fragmented
What are the childhood vaccines?
(infanrix-hexa) D T aP IPV HepB HiB: 6 vaccination in one injection
- diphtheria, tetanus, acellular pertussis, inactivated polio, haemophilus influenzae type B, hepatitis B
- All sub-unit or component vaccines
- Given early (6wks, 3mths, 5 mths, 4yrs)
M M R: Measles Mumps Rubella
- All live virus vaccines
- Given at 15mths (and 4 yrs)
What is tetanus? whats tetani and it’s symptoms?
- Clostridium tetani: anaerobic, spore-forming, Gram-positive bacillus, penicillin-sensitive
- Spores everywhere, particularly manure/soil
- Easily introduced at time of injury, especially deep penetrating dirty wounds
Toxin symptoms (bacteria symptoms are trivial)
- ~10 days post exposure via wound
- muscular rigidity caused by tetanospasmin toxin
Clinical features:
- arching of back, facial grimace ‘lock jaw’
Where are the highest rates of tetanus immunity and why?
- Uncommon in the developed world due to universal immunisation (34 cases in NZ: 2000-2010)
- Higher risk >60yrs, when immunity has waned ( you need boosters)
- Major problem in the developing world: ~300 000 per year, due to poor vaccination
- >50% tetanus deaths are in the developing world
- entry via umbilicus to infant of incompletely or unimmunised mother
- infant has no ‘passive immunity’ of IgG passed through fromt the mother
- failure of aseptic technique, >90% mortality
How does WHO plan to diminsh the high rates of neonatal tetanus in developing countries?
Give all women of child-bearing age in high risk areas 3 doses of tetanus toxoid. Also passive immunisation via human or equine tetanus immunoglobulin (TIG)
- acquire immunity by transfer of serum (Ig) from a donor to a non-immune person
- neutralises unbound toxin
- shortens the course, lessens the severity of disease, improves survival
- required if dirty would and no previous tetanus immunisation
What are the advantages and disadvantages of Passive Immunisation
Advantages
- immediate protection
Dis-advantages:
- No long term protection
- Risk of transmission from other disease from donor
- expensive and not always easily available
- serum sickness (side-effects) from injection of another persons serum
Good INITIAL prophylaxis and then followed up by a full vaccination
What is the proper name for ‘whooping cough’ and what is it?
Bordetella pertussis
- Gram negative bacilli (cocci-bacillus) that’s among 10 of the most common causes of death due to an infectious disease; and a leading cause of vaccine preventable death
- ~50mill cases causing 350,000 deaths annually, 90% in 3rd world
- highest mortality in 1st year of life
- highly contagious, household spread upto 90%
How do you get pertussis and what is it’s clinical manifestations?
Deposited in respiratory tract by aerosol droplets from sneezing/coughing; very infectious
- Catarrhal phase (1-2 wks); runny nose, conjunctival infection, malaise
- Paroxysmal phase (1-10 wks): short expiratory burst of rapid couhgs, then inspiratory gasp and high-pitched whoops (uncomon in infants and adults)
- Convalescent phase (wks-months); recovery
Complications and treatment of Pertussis
- secondary bacterial infections such as pneumonia
- encephalopathy, seizures, apnoea
Treatment:
- Erythromycin (macrolide AB)
- May shorten illness if started early (during 1st few weeks)
- Decreases infectivity but does little in established illness
What are the pertussis vaccines?
- Whole cell vaccine (NO LONGER USED)
- killed whole cell vaccine
- efficacy 80%
- introduced in NZ 1945
- major limitation; systemic and local reactions
- Acellular vaccine
- used since August 2000
- contains a number of virulence factors and antigens isolated
- efficacy of NZ vaccine ~85%
- 3-dose primary schedule and 2 boosters
Stats of Pertussis in NZ
- about 1 death per year
- 7000 cases from 1999-2000
- infants at highest risk of complications and death if no maternal antibodies via placenta or breastfeeding
- Nearly 90% coverage by 2 yrs, but only 50% get 3rd dose at 5mths : didn’t get the booster!!
- this need for multiple doses and the protection waning is why it’s still prevalent in NZ
- Immunisation gives 80% protection to 6yrs, immunity wanes 5-10years
Recommended for Pertussis Vaccine; who should get it?
- Parent and other adults living in the households with young children
- family members (particularly parents ) as these are the source of infection in > 50% of cases
- Adults working with children (teachers etc)
- Health care workers, especially those working with newborns
What is Poliomyelitis from Polio virus and what does it do?
- Destrys LMN resulting in paralysis
- predominatly affects children under 5
- 1/200 leads to irreversible paralysis (legs), 5-10% die from resp difficulty
- in 2008: endemic in afganistan, India, Nigeria and Pakistan
- COULD BE ELIMINATED BY VACCINATION
Desribe the Live Oral Poliovirus Vaccine
- OPV used where polio endemic
- Intestinal immunity, controls of wild-virus circulation
- **Rare; vaccine associated paralytic polio disease VAPP (1 case for every 2.4mill doses)
Describe the Inactivated polio vaccine
- 99% effective with 3 doses
- most countries use this instead of OPV
- NZ changed to IPV in 2002
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Fever and a New Murmur: Endocarditis15
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Diarrhoea and Acute Gastrointestinal Illness19
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Fever and Cough: Pneumonia18
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Infection and Immunity23
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Peritonitis and Intra-Abdominal Infection20
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Immunisation25
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Fever and Rash; Vaccine Preventable Disease27
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Factors Affecting Immune Response20
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Dysuria: Urethritis, Cervicitis and Testicular Pain32
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Fever and Lymphadenopathy20
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Hypersensitivity and Autoimmunity28
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Acquired Immune Deficiency and Headache18
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Genital Ulcers and Genial Lesions27
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Molecular Medicine: A Case of Febrile Neutropenia11
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Febrile Returned Traveller17
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Fever and a Headache1
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Dysuria: A urinary tract infection23
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Post Operative Complications: Healthcare Associated Infections29
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Patient with Jaundice: Viral Hepatitis25
