Re: Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial
We would like to express our gratitude to Zimakoff and their team for providing us with the data we requested on July 28, 2023 regarding the time between the diphtheria-tetanus-pertussis-containing (DTP) vaccine and the measles-mumps-rubella (MMR)/placebo vaccination. We were particularly interested in studying the possible impact of this interval on morbidity in their Danish randomised controlled trial (RCT) of MMR (1). In previous studies conducted in Guinea-Bissau, it was observed that a short interval between these two vaccines could diminish the beneficial effects of the early measles vaccine (MV) (2-4). Consequently, in our own RCTs investigating the potential non-specific effects (NSEs) of MV on mortality (2-5), we have implemented a mandatory minimum interval of 28 days between DTP and MV. We have recently extended this interval to 42 days as well (https://classic.clinicaltrials.gov/ct2/show/NCT04899765). However, it should be noted that the Danish RCT did not employ a similar requirement, with a median interval of 28 days between DTP and MMR.
In the Danish study, severe illness was defined as being admitted to the hospital for more than 12 hours. After analyzing the available data, the researchers found that if children received MMR/Placebo within 28 days after their most recent DTP vaccination, the risk of severe illness was significantly higher for the MMR group compared to the placebo group. However, if the interval was 29 days or longer, the risk of severe illness was similar between the MMR and placebo groups. When looking at all hospital contacts as the outcome, the risk ratios were not significantly different between the two groups.
The accidental discovery made by the Danish RCT unintentionally supported the idea that there are non-specific effects (NSEs) associated with vaccines, as it supported previous evidence that a small time gap between DTP and MMR vaccinations could lead to adverse effects (2-4). This finding contradicts the belief that vaccines only have specific effects.
Peter Aaby, Lise Gehrt, Sebastian Nielsen, and Christine Stabell Benn from the Bandim Health Project in Guinea-Bissau and the University of Southern Denmark. (Contact: [email protected])
Citations 1. Zimakoff AC, Jensen A, Vittrup DM, et al. Research on the measles, mumps, and rubella vaccine given at 6 months of age and the likelihood of being hospitalized for infection before 12 months: a study where participants were randomly assigned to different groups. BMJ 2023;381:e072724 2. Aaby P, Martins CL, Garly ML, et al. Study on the non-specific effects of the standard measles vaccine given at 4.5 and 9 months of age on childhood mortality: a randomized controlled trial. BMJ 2010;341:c6495 3. Garly ML, Trautner SL, Marx C, et al. Investigation on the size of the thymus at 6 months of age and the subsequent mortality rate in children. J Pediatr 2008;153:683-8 4. Nielsen S, Fisker Ab, da Silva I, et al. Assessing the impact of early two-dose measles vaccination on childhood mortality and considering the influence of maternal antibodies in Guinea-Bissau, West Africa: a single-center open-label randomized controlled trial. EClinicalMedicine 2022;49:101467 5. Fisker AB, Nebie E, Schoeps, et al. Conducting a randomized trial at two centers to study the effects of an additional early dose of measles vaccine on mortality and measles antibody levels. Clin Infect Dis 2018;66:1571-80 6. Gehrt L, Benn CS. Response to the article "Measles, mumps, and rubella vaccine at age 6 months and hospitalisation for infection before age 12 months: randomised controlled trial." BMJ 2023;381:e072724. Rapid response 18 July 2023
