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What can carriage studies
tell us?
Dr Caroline Trotter
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.
Transmission of Nm, Hi, Sp
Exposure

Invasion

Acquisition

Disease

Recovery

Colonisation
Epidemiology of carriage
• E.g. Meningococcal carriage prevalence by age

Christensen et al, 2010, Lancet ID
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
Hib
Change in carriage prevalence after vaccination

Gessner & Adegbola, Vaccine 2008
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
Streptococcus pneumoniae
Herd immunity
Observed cases
Predicted cases (with herd immunity)
Predicted cases (no herd immunity)

19
98
/9
9
19
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/0
0
20
00
/0
1
20
01
/0
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20
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/0
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9

1000
900
800
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600
500
400
300
200
100
0
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
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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Carriage studies - what do they add? Human bacterial challenge experiments as an alternative

  • 1. What can carriage studies tell us? Dr Caroline Trotter
  • 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. Transmission of Nm, Hi, Sp Exposure Invasion Acquisition Disease Recovery Colonisation
  • 4. Epidemiology of carriage • E.g. Meningococcal carriage prevalence by age Christensen et al, 2010, Lancet ID
  • 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. Hib Change in carriage prevalence after vaccination Gessner & Adegbola, Vaccine 2008
  • 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
  • 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. 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. 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…