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Collin Yong, a paediatrician in Vancouver, British Columbia, described the present case and posed the question. A public health nurse checked the immunization history of a child in kindergarten and told the parents that the child’s varicella vaccination was invalid because it was given too soon (26 days) after the measles, mumps and rubella (MMR) vaccination. They were advised to repeat the vaccination to be more certain of protection. The parents were upset to learn that their child might not be protected. The family doctor was also upset because he believed he had been exemplary in advocating for the use of a new and somewhat controversial vaccine. His question to the paediatrician was whether giving varicella vaccine within four weeks after the MMR vaccination actually reduces protection – what is the evidence for this?
The Canadian Immunization Guide (1) advises that MMR and varicella vaccinations should be given at the same time or separated by at least four weeks. These alternative schedules elicit equivalent immune responses to all four antigens (2). The concern regarding a shorter separation interval first arose when reduced responsiveness to smallpox vaccination was noted in children recently given the measles vaccine (3). Fireman et al (4) showed that the administration of a live attenuated measles vaccine suppressed delayed hypersensitivity responses for one to four weeks and interfered temporarily with the in vitro response capacity of peripheral blood lymphocytes. Suppression of cell-mediated immunity after natural measles is substantial (5), providing biological plausibility for an effect after MMR vaccination. Support for an effect on varicella vaccination is limited to a retrospective cohort study (6) of breakthrough varicella infections (vaccine failures) in vaccinated American children. When varicella vaccination followed MMR vaccination by fewer than 28 days, breakthrough infection occurred three times more frequently (95% CI 1.5 to 6.4) than after greater separation of the vaccinations. Given that breakthrough infection may occur in 3% to 4% of Canadian children annually after a single dose of varicella vaccine (7), mistiming the vaccination could increase the risk of breakthrough infection to as high as 10% to 15% per year. The public health nurse was correct to recommend a remedial dose for the child described above. The potential for response interference likely diminishes toward the end of the four-week period after MMR vaccination, but public health guidelines need to be evidence-based, and evidence only exists for separation intervals of 28 days or more. The caution only applies to live virus vaccines.
The recent availability of a combined MMR-varicella vaccine (Priorix-Tetra, GlaxoSmithKline, Canada) will facilitate concurrent vaccinations, avoiding the potential for mistiming sequential vaccinations. The movement toward routine use of two doses of varicella vaccine, as recently recommended in the United States (8), will also help to ensure that children are optimally protected.
The Upshots column in Paediatrics & Child Health is meant to address practical questions without ready answers in standard references such as the Red Book or the Canadian Immunization Guide. Readers are invited to submit questions to the Journal office. A timely response will be provided, whenever possible, from one member of a panel of experts. The most interesting exchanges will be selected for publication. Submitters should identify themselves, but will be given the option of anonymity in the published version. Submit questions directly to ac.spc@lanruoj. Please note that these may be edited for clarity and brevity.
David Scheifele MD
Associate Editor, Paediatrics & Child Health