The fundamental link between pneumococcal carriage and disease

Figures & data

Figure 1. Dependence of vaccine efficacy against disease on vaccine efficacy against acquisition.

The dependence is plotted with different levels of vaccine efficacy against carriage progression to disease (VE_P = 90, 80, 70, 60, 50, 40, 30 and 0% from top to bottom). For smaller values of VE_p, the lines are steeper, indicating a larger predictive value of carriage as marker of the direct protection against disease in the individual (see text). VE_acq: Vaccine efficacy against acquisition; VE_D: Vaccine efficacy against disease; VE_p: Vaccine efficacy against carriage progression to disease.

Table 1. Pneumococcal conjugate vaccine trials with data on the concurrent direct vaccine effect on colonization and disease.

Trial site/population/vaccine (carriers)^†	Vaccine schedule	Disease end points and vaccine efficacy	Impact of vaccination on carriage^†	Notes	Ref.
South Africa (HIV infected and uninfected) PCV9 (CRM)	6–10–14 weeks	HIV-uninfected: IPD: 83 (39–97)%; Pneumonia (radiol): 20 (2–35)%	At 9 months: VT: vaccinated 18%, unvaccinated 36% (p < 0.001) NVT: 36 versus 25% (p = 0.007)	The carriage study was done prior to the efficacy trial and was among mainly HIV-uninfected children	[113,114]
The Gambia PCV9 (CRM)	3 doses starting at 6–51 weeks	VT IPD: 77 (51–90)%; Pneumonia: 37 (27–45)%	RR at 9–15 months: VT: 0.56 (0.49–0.65); NVT: 1.59 (1.41–1.79)	Large sample size in the carriage study; serotype-specific data available	[115,116]
USA/American Indians PCV7 (CRM)	3 doses starting at 6 weeks to 7 months, a booster at 12–15 months catch-up cluster randomized	VT IPD: 76.8 (9.4–95.1)%; VT AOM: 64 (−34–90)%	OR at 7 months: VT: 0.40 (0.23–0,67), NVT: 0.72 (0.43–1.23) OR at 12 months: VT: 0.51 (0.34–0.78), NVT: 1.02 (0.61–1.72) OR at 18 months: VT: 0.81 (0.51–1.31), NVT: 1.67 (1.02–2.78)		[117–119]
Czech Republic and Slovakia PCV11 (Hi protein D)	2–4–6–12 months	VT AOM: 57.6 (41.4–69.3)% NVT AOM: 8.5 (−64.2–49.0)%	After booster: VT: 42.8 (16.7–71.9)%; NVT: 15.3 (−78.9–59.7)%	Efficacy against carriage detected later than efficacy against AOM	[126,127]
Finland two PCV7s (CRM and OMPC)	2–4–6–12 months	PncOMP: VT AOM: 56 (44–68)%; NVT AOM: -27 (−70–6)% PncCRM: VT AOM: 57 (44–67)%; NVT AOM: -33 (−80–1)%	PncCRM: at 12 months 17% (VT, NS) At 18 months: VT: p < 0.001, NVT increase: p = 0.02	No published data on carriage available. Efficacy against carriage detected later than efficacy against AOM	[124,125]
The Philippines PCV11 (D/T)	6–10–14 weeks	Radiol. Pneumonia: 22.9 (−1.1–41.2)%	At 24 months: VT: 35 (8–54)%; NVT: no effect	No published data on carriage available	[120,121]
Argentina, Panama, Colombia/PCV10 (Hi PD/D/T) 23738/2000	2, 4, 6 and 15–18 months	Likely bacterial community-acquired pneumonia: 18 (6–29)% WHO pneumonia: 23 (9–36)%	At 7 months: VT: 18 (−7–37)%; NVT: -15.2 (−55–14) At 12 months: VT: 28 (5–48)%; NVT: 3 (−32–29) 3 months post-booster: VT: 28 (2–57)%; NVT: -28 (−78–7) 9 months post-booster: VT: 29 (−0.2–49)%; NVT: -22 (−74–15) Any visit: VT: 26 (13–37)%; NVT: -6 (−25–10)	Carriage trial in Panama only; no published data available	[122,123]
Israel/day care attendees PCV9 (CRM)	Toddlers 2 doses for those <1 year, 1 dose for older	RR: URI 0.85 (0.75–0.97) LR: 0.84 (0.72–0.98) AOM: 0.83 (0.67–1.02) Use of antibiotics: 0.85 (0.75–0.97)	OR 1 month post-PCV9: VT: 0.50 (0.3–0.66); NVT: 1.59 (1.28–1.96)	Disease end points are not pneumococcus specific serotype-specific carriage data for some VT serotypes	[128,129]

^†The trial-specific data are given in several ways: either % protection, RR or OR, with 95% CI.

AOM: Acute oitis media; CRM: Nontoxic mutant of diphtheria toxin; D: Diphtheria toxoid; Hi protein D: Protein D of H. influenzae; IPD: Invasive pneumococcal disease; NVT: Nonvaccine serotype; OMPC: Outer membrane protein complex of N. meningitidis; OR: Odds ratio; PCV: Pneumococcal conjugate vaccine; RR: Risk ratio; T: Tetanus toxoid; VT: Vaccine serotype.