One priming dose of PCV10 still holds at five and a half years

Design

long-term follow-up of a four-arm cluster-randomised controlled trial, tested for non-inferiority at a 5 percentage point margin

Population

49644 participants in 24 communes in Nha Trang, Viet Nam, including infants, toddlers, preschool children and adult caregivers, 5.5 years after PCV10 introduction

Primary outcome

prevalence of PCV10-type nasopharyngeal carriage in vaccine-eligible infants aged 4 to 11 months and toddlers aged 14 to 24 months

Effect

infants 0.7% (1p+1) vs 1.9% (2p+1) vs 0.9% (3p+0); difference -1.2 pp (95% CI -3.0 to 0.6) for 1p+1 vs 2p+1, non-inferior in all comparisons

Twenty-four communes in Nha Trang, Viet Nam, were randomly assigned to one of four PCV10 infant schedules - 0p+1, 1p+1, 2p+1 or 3p+0 - with three unvaccinated communes as observational comparison. This long-term follow-up reports nasopharyngeal carriage 5.5 years after introduction, across 49644 participants including 10423 infants, 10988 toddlers, 9580 preschool children and 18653 adult caregivers.

Vaccine-type carriage at 5.5 years was 0.7% in 1p+1 infants, 1.9% in 2p+1 and 0.9% in 3p+0; in toddlers, 0.9%, 0.6% and 1.0%. The 1p+1 schedule met non-inferiority against both three-dose schedules in every infant and toddler comparison, with a margin of 5 percentage points and observed differences well inside it. The single-dose 0p+1 schedule met non-inferiority in seven of eight intention-to-treat comparisons. The share of pneumococcal carriers carrying vaccine-type serotypes fell in infants from 52.1% to 7.6%, in toddlers from 50.0% to 4.0%, and in adult caregivers from 39.4% to 10.5% - indirect protection at the same rate as the direct effect.

This is the durability evidence a programme needs before dropping a dose. The caveat the authors put first is the setting: these findings apply to programmes already established, with a catch-up campaign behind them, not to a country introducing PCV from scratch. The outcome is carriage, not invasive disease - a well-validated intermediate, but an intermediate. Where a national programme already runs a two-dose-plus-booster schedule with good coverage, this is the evidence for asking whether the second priming dose is still buying anything.

• Read this as programme-level evidence: it is about schedules, not about an individual child's next appointment.
• The finding applies to established programmes with a catch-up campaign behind them, not to new introductions.
• Carriage is the outcome measured; invasive disease was not, so treat the inference as one step removed.
• Indirect protection in unvaccinated adult caregivers was as strong under 1p+1 as under three-dose schedules - that is the load-bearing result.
• Fifty serious adverse events were reported within a month of vaccination and none was judged vaccine-related.

The statistics, in plain English

Non-inferiority here was defined as the upper bound of the 95% confidence interval for the difference in carriage prevalence not exceeding 5 percentage points, and the observed differences - for instance -1.2 pp (95% CI -3.0 to 0.6) for 1p+1 against 2p+1 in infants - sit comfortably inside it. Note how small the denominators are at this timepoint: 2 of 286 infants carrying vaccine-type pneumococcus means the percentages move a lot with one or two children, which is why the intervals are wider than the headline suggests. Carriage is a surrogate for invasive disease, well-supported as one, but a schedule change should be judged on that chain of reasoning rather than on a direct disease outcome.

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