One-fifth doses of yellow fever vaccine held up in children under two

Design

phase 4, single-blind, randomised 1:1:1 non-inferiority trial (5 percentage point margin)

Population

1,784 children aged 9–23 months in Kampala, Uganda, median age 13 months

Primary outcome

seroconversion at 4 weeks by 50% plaque reduction neutralisation test

Effect

one-half vs full dose difference −0.17 (95% CI −0.52 to 0.17); no difference for one-fifth vs full

Fractional dosing is how outbreak responses stretch a vaccine supply that cannot be expanded quickly, and yellow fever is the standing example. Evidence supported it in adults and older children, but not in the youngest age group routinely vaccinated. This phase 4 trial in Kampala randomised 1,784 children aged 9 to 23 months, in three age strata, to one-fifth (0.1 mL), one-half (0.25 mL) or full (0.5 mL) doses of 17DD yellow fever vaccine.

The primary outcome was non-inferiority of seroconversion at four weeks, measured by 50% plaque reduction neutralisation test, against a five percentage point margin. Both fractional doses met it: there was no difference in seroconversion between the one-fifth and full doses, and a difference of −0.17 (95% CI −0.52 to 0.17) between the one-half and full doses. Follow-up at one year and beyond is part of the trial design.

The practical reading is narrow and important. This supports fractional dosing for outbreak response during supply shortage — not a change to routine immunisation schedules, and not a statement about how long protection lasts. For clinicians in India, where yellow fever vaccination is required for travellers to and from endemic countries and is given at designated centres, the relevance is chiefly in understanding why a certificate issued during an outbreak response abroad may record a fractional dose.

• Fractional dosing is an outbreak-response measure, not a routine schedule change
• Seroconversion at four weeks is an immunological endpoint, not documented disease protection
• Check what dose is recorded on an international certificate of vaccination presented by a traveller
• Note the trial enrolled only children without prior yellow fever vaccination or disease
• Duration of protection after a fractional dose in this age group is still being followed up

Why it matters

It removes the youngest age group as the reason a fractional-dose campaign could not be run.

Don't overread it

Seroconversion at four weeks is a surrogate — this does not establish equivalent duration of protection.

The statistics, in plain English

Non-inferiority trials ask a different question from superiority trials: not whether the fractional dose is better, but whether it is not worse by more than a pre-agreed margin — here five percentage points. The observed difference of −0.17 with an interval of −0.52 to 0.17 sits far inside that margin, so the conclusion holds. What a non-inferiority result cannot tell you is anything about outcomes the trial did not measure, which is why the duration-of-protection follow-up matters.

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