Carriage studies - what do they add? Human bacterial challenge experiments as an alternative

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Dr Caroline Trotter's presentation at Meningitis Research Foundation's 2013 conference, Meningitis & Septicaemia in Children & Adults

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Carriage studies - what do they add? Human bacterial challenge experiments as an alternative

  1. 1. What can carriage studies tell us? Dr Caroline Trotter
  2. 2. Why do we need carriage studies? • Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae are carried in the human pharynx and transmitted through droplets • Most infections result in a period of carriage and only a small minority result in disease • Many microbial, host and environmental factors influence the likelihood that a pharyngeal infection will progress to invasive disease and the distribution of clinical cases may not accurately reflect the pattern of transmission • Knowledge of carriage is essential understanding epidemiology of infection and in rational planning of vaccination strategies.
  3. 3. Transmission of Nm, Hi, Sp Exposure Invasion Acquisition Disease Recovery Colonisation
  4. 4. Epidemiology of carriage • E.g. Meningococcal carriage prevalence by age Christensen et al, 2010, Lancet ID
  5. 5. Effect of conjugate vaccines • The effect of conjugate vaccines on reducing vaccine-type carriage in controlled trials or before and after studies is now well established • Hib, MenC, pneumococcal and most recently MenA
  6. 6. Hib Change in carriage prevalence after vaccination Gessner & Adegbola, Vaccine 2008
  7. 7. Neisseria meningitidis • Reduction in group C carriage in UK teenagers • Reduction in group A carriage following MenAfriVac in Burkina Faso Kristiansen et al. CID 2013 Maiden et al, JID 2008
  8. 8. Streptococcus pneumoniae
  9. 9. Herd immunity Observed cases Predicted cases (with herd immunity) Predicted cases (no herd immunity) 19 98 /9 9 19 99 /0 0 20 00 /0 1 20 01 /0 2 20 02 /0 3 20 03 /0 4 20 04 /0 5 20 05 /0 6 20 06 /0 7 20 07 /0 8 20 08 /0 9 1000 900 800 700 600 500 400 300 200 100 0
  10. 10. Challenges of conventional approaches • Role of and need for carriage studies is widely appreciated, but… • Many factors can influence the epidemiology of carriage • Large and expensive studies needed to measure change in (low) prevalence following vaccination • Before and after studies don’t point to mechanisms of protection • Immunological correlates of carriage not well defined
  11. 11. Should we go further? • Carriage as an endpoint for licensure? • Carriage as a bridge to understand epidemiology where surveillance poor? • Estimating carriage effect at an earlier time point? • TpmA…

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