Rabies vaccine is associated with decreased all-cause mortality in dogs

Abstract

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 (0-3months, 4-11months, and 12months 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 0-3months, by 44% (95% CI=21-60%) in dogs aged 4-11months and by 16% (95% CI=0-29%) in dogs aged 12months and older. We hypothesize that the protective association between rabies vaccination status and all-cause mortality is due to a protective effect of rabies vaccine against diseases other than rabies. Existence of a strong non-specific protective effect of rabies vaccine on mortality in dogs would have implications for the design of dog rabies control programs that aim to eliminate dog-mediated human rabies cases. Further, we propose that owned domestic dogs in high mortality settings provide a useful animal model to better understand any non-specific protective effect of rabies vaccine in children, due to dogs' high numbers, high morbidity and mortality rates, relatively short lifespan, exposure to a variety of infectious and parasitic diseases, and shared environment with people.

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

“…We previously reported results from an observational study in the same population as the current randomized trial [25]. Controlling for the effects of sex and number of dogs in the residence, and stratifying by age, we found that owner-reported rabies vaccination was associated with a lower risk of death from any cause [25].…”

“…Although the randomized, owner-blinded, placebo-controlled design used in the current study provides a more rigorous assessment of the true effect of vaccination on survival than our previous observational study [25], the current study is not without its limitations. The study was designed to detect an overall effect of vaccination on survival, and not effect modification by sex.…”

“…The required sample size was estimated for the survival analysis, based on a significance level of 5%, power of 80%, and an effect size (hazard ratio) of 0•33, with a fixed follow-up time of 7 weeks. The probability of death over this period was estimated from the observed mortality rates in the 0−3 month age group from the health and demographic surveillance system [25], assuming exponential survival times [26]. With an expected loss to follow up of 25%, we arrived at a required sample of 354 puppies.…”

Non-specific effects of rabies vaccine on the incidence of common infectious disease episodes: study protocol for a randomized controlled trial

“…Recently, it was proposed that rabies vaccine (a non-live vaccine) has protective NSEs in people and in animals [7][8][9]. A recent RCT evaluated the RTS,S malaria vaccine using two parallel age groups: 6 to 12 weeks and 5 to 17 months, with the former control population receiving a serogroup C meningococcal conjugate vaccine and the latter rabies vaccine.…”

“…Among several possible explanations, one is that rabies vaccine provide a protective benefit [7,8]. In the age group for which rabies vaccine was used as a control, the control group had 90% lower incidence of meningitis and approximately 50% lower incidence of cerebral malaria In a population-based cohort study, rabies vaccine was shown to be associated with decreased all-cause mortality in free-roaming dogs in a high-mortality setting [9]. Compared to the unvaccinated group, all-cause mortality rates in the vaccine group were lower by 56%, 44% and 16% in young, adolescent and adult dogs, respectively.…”