Results

Question 1

CSF

Answer 1

NICE guidelines - prompt recognition of signs and symptoms of meningitis and meningococcal disease is key to saving lives

Question 2

Treatment -Fungal meningitis

Answer 2

 Amphotericin B
 Flucytosine
 Fluconazole

Question 3

Viral meningitis

Answer 3

• no specific antiviral therapy, but Aciclovir for herpes simplex virus
  arely causes long-term problems

Question 4

Bacterial

Answer 4

• initial empirical therapy
   Transfer patient to hospital urgently
   If meningococcal disease suspected, use benzylpenicillin (narrow spectrum but
  has activity against niceria) – cefotaxime or chloramphenicol
   Consider adjunctive treatment with dexamethasone – see contraindications e.g.
  septic shock, meningococcal septicaemia
   If unknown bacteria for 3 months to 50 years – use cefotaxime or ceftriaxone and
  consider adding vancomycin
   Unknown bacteria for more than 50 years – use cefotaxime or ceftriaxone plus
  amoxicillin, possibly with vancomycin

Question 5

Bacterial meningitis – many recover fully if treated early but can result in serious long-
term issues:

Answer 5

 Hearing or vision loss – partial or total
 Issues with concentration or memory
 Epilepsy
 Co-ordination, movement and balance issues
 Loss of limbs

Question 6

Antibiotic treatment

Answer 6

• Meningocci- Benzylpenicillin or cefotamine
• Pneumococci - cetotaxamine or benzylpenicillin or if resistant to vancomycin
• H.influenzae - cetotaxamine- for type b give firampicin for 4 days before hospital discharge
• Listeria - Amoxicillin oe ampicillin or gentamicin or co- trimoxazole

CONSIDER ADJUNCTIVE TREATMENT WITH DEXAMETHASONE

Question 7

septicaemia can kill in under 4 hours

Answer 7

The bacteria multiply in the body with alarming speed, overwhelming the immune system
Early symptoms can be flu-like, making it extremely difficult to diagnose and sometimes people show no symptoms at all
Prevention is better than the cure in this case

Question 8

A number of vaccines exist that can prevent many cases of meningitis, both viral and bacterial including:

Answer 8

 The measles, mumps and rubella (MMR) vaccine
 The DTaP/IPV/Hib vaccines
 The pneumococcal conjugate vaccine (PCV)
 The Hib/Men C vaccine
 The Men W vaccine
 The Men B vaccine

Question 9

Public Understanding of Risks/Benefits of Vaccines

Answer 9

 Most scientists think about risk in terms of populations
 Most patients will think about the risk to themselves/their child
 To gain herd immunity (protecting the community) people must think beyond the individual
 People weigh up the perceived risks against the perceived benefits of actions – some people may not fully understand the risks and benefits
 Many things influence risk perception
 The source of information
 How the data is presented
 People categorising risk numbers
 The Department of Health (1997) issued guidelines on best practice
 Comparisons help provide a sense of perspective
 Relative risks can be seriously misleading and if they are used – baseline rates
must be included

Question 10

Options for parents/carers about MMR vaccine

Answer 10

 Vaccinate
 Delay vaccination
 Use single vaccinations
 Homeopathic vaccines
 Don’t vaccinate

Question 11

Mutation occurs in specific genes

Answer 11

If antigens inducing protective immunity is known – can genetically manipulate
pathogen genome to create safer, more potent vaccine
 Example may be “universal flu vaccine” – create mutations in hemagglutinin and
neuraminidase genes to create vaccine based on prevalent strain

Question 12

Example of attenuated and inactivated vaccines – the polio vaccines

Answer 12

 2 types of polio vaccines in use
 The Salk vaccine, or inactivated poliovirus vaccine (IPV), is grown in cultured cells
(vero cells) then chemically inactivated (killed) with formalin
 2 injections of IPV protect 90% of individuals and 3 shots protect 99% of people
against PV1, 2 and 3
 The other vaccine and can be taken orally
 Oral polio vaccine (OPV) is an attenuated virus, weakened by passage through
animal cells
 It is given orally on a sugar lump
 Another advantage is that the attenuated virus is shed in faeces – spreading
immunity in the community
 It’s ideal for mass vaccination

Question 13

proteins 1:

Answer 13

toxoids
 The pathogenicity of some bacteria, Clostridium tetani (tetanus) due to secreted
toxins
 These induce a powerful Th2-type response (ab), which can be reproduced by
inactivating such toxins by treating them with formalin
 These detoxified toxins, called toxoids, safe for use in vaccines – neutralising
antibodies are produced in response to a subsequent infection that bind to and
complex the bacterial toxins, inactivating them
 Toxoids can be created using genetic engineering – new vaccines in pipeline

Question 14

Purified proteins 2: others

Answer 14

 A humanised IgG Man (Palivizumab) is used to treat severe respiratory syncytial virus
(RSV) infection in infants by passive immunisation
 The Mab binds to the F (fusion) protein on RSV, thus preventing the virus binding to
receptors on target cells which it would use for entry
 RSV is unusual, as antibody titres in response to infection in young children (0-2 years) are very low and re-infection is common
 As such, it is the leading cause of infant mortality amongst paediatric infections
 Vaccines are under development, based on inducing antibody and/or CTL (cytotoxic
T-lymphocytes) responses to the F protein or surface glycoprotein, but results have been very equivocal

Question 15

Recombinant proteins

Answer 15

 Subunit vaccine are composed of specific
antigens or epitopes that induce potent and
specific protective humoral or CTL responses
 As they only contain specific antigens/epitopes
from the pathogen, there are less side effects

Question 16

Once key antigens/epitopes are identified,

subunit vaccines can be made by:

Answer 16

 Chemical fractionation of intact microbe,
followed by purification and stabilisation of key antigens, and, if required, chemical linkage of antigens
 If key epitopes are known, can manufacture as peptides by linking amino acids in specific sequence – 3D epitopes can be created using scaffolds
 By using recombinant DNA technology, any
genetic construct coding for antigens,
polyepitopes or both can be expressed as soluble proteins or glycoproteins – vaccines produced this way are called recombinant subunit vaccines

Question 17

Self-assembling proteins – virus-like particles

Answer 17

 HPV causes cervical cancer
 Strains 16 and 18 are the commonest and most oncogenic
 The major antigen in HPV in the L1 capsid protein
 When expressed as a recombinant protein in yeast or insect cells. The L1 protein
spontaneously-assembles into a virus-like protein (VLP)
 VLP-based vaccines are available – Gardisil (with L1 proteins from strains 6, 11, 16
and 18 made in yeast)

Question 18

Polysaccharide vaccines

Answer 18

 Encapsulated bacteria Neisseria meningitides, Haemophilus influenza and
Streptococcus pneumoniae (NHS) are important pathogens that cause disease
especially among infants, the elderly and immunocompromised persons
 They have a slimy layer or capsule around them, composed of polysaccharides
 These are highly antigenic and are used in vaccines
 They are sugar antigens instead of protein antigens – so immune response is T-cell
independent
 These polysaccharide vaccines developed against NHS and Salmonella typhi, provided little immunity in infants and young children as they can’t induce T-cell independent humoral responses and create memory cells

Question 19

Glycoconjugate vaccines

Answer 19

By chemically coupling the polysaccharide capsular antigens from NHS to a carrier protein, a glycoconjugate vaccine is formed
 The carrier protein is the toxoid form the tetanus or diphtheria organisms
 Using the same carrier proteins contained in the Hib conjugate vaccines, a whole
new range of meningococcal and pneumococcal conjugate vaccines, safe and potent for use in young children, was developed

Question 20

Effects of routes of vaccination

Answer 20

 Most vaccines are given by injection
 Vaccines may be painful, expensive and unpopular
 Immunologically, they may not stimulate optimal immune response as most
pathogens enter via mucosa e.g. gut (salmonella, E. coli), respiratory mucosa (flu,
rhinovirus) or genital/anal mucosa (HIV, bacterial STIs, Chlamydia)
 If given orally or nasally, may overcome many issues
 Now it is known that adjuvants can pay key role in directing response to appropriate
By chemically coupling the polysaccharide capsular antigens from NHS to a carrier protein, a glycoconjugate vaccine is formed
mucosa

Question 21

Role of adjuvants

Answer 21

 Many soluble proteins are poorly immunogenic when used as a vaccine
 Adjuvants enhance immunogenicity of the protein antigens in 2 ways
1. By converting soluble proteins in particles – can use alum (which sticks to the proteins), mineral oils (emulsifies the proteins) or Quil A detergent (forms colloids with proteins)
2. Effect is enhanced by inducing bacterial components – activates APCs and/or induces cytokine production and enhances inflammatory responses
 There is a need for new vaccines primarily due to antibiotic resistance
 Also prevention is better than cure and to combat new threats e.g. Ebola

Question 22

Key points

Answer 22

 The major classes of vaccines
 Attenuated
 Inactivated
 Purified proteins
 Recombinant proteins
 VLPs
 Polysaccharides
 Glycoconjugates

Question 23

more points:

Answer 23

 New classes of vaccine were required for new pathogenic targets and for specific groups
 Inactivated vaccines are the safest, but may show lower immunogenicity than attenuated vaccines
 Attenuated vaccines have the risk of reversion to virulence in immune-compromised groups e.g. pregnant women, children, elderly, immunosuppressed/HIV patients
 Immunogenicity can be enhanced by the addition of adjuvants, which act on the
innate immune pathways
 Many pathogens enter at mucosal surfaced – vaccines can be targets here by using
oral/nasal/anal/vaginal vaccines including appropriate adjuvants
 New generation vaccines are increasingly based on specific antigens or even epitopes from those antigens rather than the whole organism – these are provided by purified
proteins or polysaccharides form the organism or created by genetic engineering
 New vaccine strategies are needed to deal with complex, intractable pathogens such
as HIV, TB and malaria – these involve determining correlates of protective immunity, optimising immunogens and developing a vaccination strategy
 Clinical trials establish vaccine efficacy