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Evidence suggests that rabies vaccine may have non-specific protective effects in animals and children. We analyzed four years of data (2012–2015) from an observational study of the health and demographics of a population of owned, free-roaming dogs in a low-income community in South Africa. The objective of this analysis was to assess the association between rabies vaccine and all-cause mortality in dogs, stratified by age group (0–3 months, 4–11 months, and 12 months and older), and controlling for the effects of sex and number of dogs in the residence. Rabies vaccination reduced the risk of death from any cause by 56% (95% CI = 16–77%) in dogs aged 0–3 months, by 44% (95% CI = 21–60%) in dogs aged 4–11 months and by 16% (95% CI = 0–29%) in dogs aged 12 months and older. We hypothesize that the protective association between rabies vaccination status and all-cause mortality is due to a …