Arega, SintayehuConan, AnneSabeta, Claude TauraiCrafford, Jan ErnstWentzel, Jeanette MariaReininghaus, BjornBiggs, Louise JoanneLeisewitz, Andrew L.Quan, MelvynToka, FelixKnobel, Darryn Leslie2021-04-062021-04-062020-03Arega, S., Conan, A., Sabeta, C.T. et al. 2020, 'Rabies vaccination of 6‐week‐old puppies born to immunized mothers: a randomized controlled trial in a high‐mortality population of owned, free‐roaming dogs', Tropical Medicine and Infectious Disease 5(1): 45, doi: 10.3390/tropicalmed5010045.2414-6366 (online)10.3390/tropicalmed5010045http://hdl.handle.net/2263/79312Supplementary Materials: Table S1. Results of sensitivity analysis for survival analysis (6 to 13 weeks of age), considering subjects reported as lost or stolen by owners as dead (n = 22); Table S2. Results of sensitivity analysis for survival analysis (6 to 13 weeks of age), censoring subjects that reportedly died from accidents (n = 5).To achieve global elimination of human rabies from dogs by 2030, evidence-based strategies for effective dog vaccination are needed. Current guidelines recommend inclusion of dogs younger than 3 months in mass rabies vaccination campaigns, although available vaccines are only recommended for use by manufacturers in older dogs, ostensibly due to concerns over interference of maternally-acquired immunity with immune response to the vaccine. Adverse effects of vaccination in this age group of dogs have also not been adequately assessed under field conditions. In a single-site, owner-blinded, randomized, placebo-controlled trial in puppies born to mothers vaccinated within the previous 18 months in a high-mortality population of owned, free-roaming dogs in South Africa, we assessed immunogenicity and effect on survival to all causes of mortality of a single dose of rabies vaccine administered at 6 weeks of age. We found that puppies did not have appreciable levels of maternally-derived antibodies at 6 weeks of age (geometric mean titer 0.065 IU/mL, 95% CI 0.061–0.069; n = 346), and that 88% (95% CI 80.7–93.3) of puppies vaccinated at 6 weeks had titers ≥0.5 IU/mL 21 days later (n = 117). Although the average effect of vaccination on survival was not statistically significant (hazard ratio [HR] 1.35, 95% CI 0.83–2.18), this effect was modified by sex (p = 0.02), with the HR in females 3.09 (95% CI 1.24–7.69) and the HR in males 0.79 (95% CI 0.41–1.53). We speculate that this effect is related to the observed survival advantage that females had over males in the unvaccinated group (HR 0.27; 95% CI 0.11–0.70), with vaccination eroding this advantage through as-yet-unknown mechanisms.en© 2020 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/4.0/).ImmunogenicityMortalityMaternally-acquired immunitySexNonspecific effects of vaccinesVeterinary science articles SDG-03SDG-03: Good health and well-beingArticle