The Lancet
Apr 12, 2014 Volume 383 Number 9925 p1269 – 1358
http://www.thelancet.com/journals/lancet/issue/current

Comment
Prevention of varicella: time for two-dose vaccination
Kristine Macartney
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Live-attenuated varicella zoster virus (VZV) vaccines have been available for decades, but their potential to reduce disease worldwide has not been fully realised. Few countries have incorporated varicella vaccination into public programmes, even though rapid and large decreases in varicella deaths and admissions have been achieved in the USA and Australia.1,2 One reason for reluctance to vaccinate is that, despite high efficacy of 88–100% reported in the randomised controlled trials of one-dose live-attenuated monovalent varicella vaccines in children (Varilrix, GSK3 and Varivax, Merck4), field effectiveness has turned out to be lower at 72–81%.
Protection against varicella with two doses of combined measles-mumps-rubella-varicella vaccine versus one dose of monovalent varicella vaccine: a multicentre, observer-blind, randomised, controlled trial
Prof Roman Prymula MD a, Marianne Riise Bergsaker MD b, Susanna Esposito MD c, Prof Leif Gothefors MD d e, Sorin Man MD f, Nadezhda Snegova MD g, Mária Štefkovičova MD h, Prof Vytautas Usonis MD i, Prof Jacek Wysocki MD j k, Martine Douha MSc m, Ventzislav Vassilev PhD m, Dr Ouzama Nicholson MD l, Bruce L Innis MD l, Paul Willems MD m
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961461-5/abstract
Summary
Background
Rates of varicella have decreased substantially in countries implementing routine varicella vaccination. Immunisation is possible with monovalent varicella vaccine or a combined measles-mumps-rubella-varicella vaccine (MMRV). We assessed protection against varicella in naive children administered one dose of varicella vaccine or two doses of MMRV.
Methods
This study was done in ten European countries with endemic varicella. Healthy children aged 12—22 months were randomised (3:3:1 ratio, by computer-generated randomisation list, with block size seven) to receive 42 days apart (1) two doses of MMRV (MMRV group), or (2) MMR at dose one and monovalent varicella vaccine at dose two (MMR+V group), or (3) two doses of MMR (MMR group; control). Participants and their parents or guardians, individuals involved in assessment of any outcome, and sponsor staff involved in review or analysis of data were masked to treatment assignment. The primary efficacy endpoint was occurrence of confirmed varicella (by detection of varicella zoster virus DNA or epidemiological link) from 42 days after the second vaccine dose to the end of the first phase of the trial. Cases were graded for severity. Efficacy analyses were per protocol. Safety analyses included all participants who received at least one vaccine dose. This trial is registered with ClinicalTrials.gov, number NCT00226499.
Findings
Between Sept 1, 2005, and May 10, 2006, 5803 children (mean age 14•2 months, SD 2•5) were vaccinated. In the efficacy cohort of 5285 children, the mean duration of follow-up in the MMRV group was 36 months (SD 8•8), in the MMR+V group was 36 months (8•5) and in the MMR group was 35 months (8•9). Varicella cases were confirmed for 37 participants in the MMRV group (two moderate to severe), 243 in the MMR+V group, and 201 in the MMR group. Second cases occurred for three participants (all in the MMR+V group). Varicella cases were moderate to severe for two participants in the MMRV group, 37 in the MMR+V group (one being a second case that followed a mild first case); and 117 in the MMR group. Efficacy of two-dose MMRV against all varicella was 94•9% (97•5% CI 92•4—96•6), and against moderate to severe varicella was 99•5% (97•5—99•9). Efficacy of one-dose varicella vaccine against all varicella was 65•4% (57•2—72•1), and against moderate to severe varicella (post hoc) was 90•7% (85•9—93•9). The most common adverse event in all groups was injection-site redness (up to 25% of participants). Within 15 days after dose one, 57•4% (95% CI 53•9—60•9) of participants in the MMRV group reported fever of 38°C or more, by contrast with 44•5% (41•0—48•1) with MMR+V, and 39•8% (33•8—46•1) with MMR. Eight serious adverse events were deemed related to vaccination (three MMRV, four MMR+V, one MMR). All resolved within the study period.
Interpretation
These results support the implementation of two-dose varicella vaccination on a short course, to ensure optimum protection from all forms of varicella disease.
Funding
GlaxoSmithKline Vaccines.