Effects of gonadectomy on the incidence rate of babesiosis and the risk of severe babesiosis in dogs aged 6 months and older at a veterinary academic hospital in South Africa: A case-control and retrospective cohort study.

Gonadectomy in dogs is associated with changes in risks of a variety of non-infectious health conditions, but few studies have examined its effects on infectious disease outcomes. The objectives of our study were to estimate the causal effect of gonadectomy on the incidence rate of babesiosis diagnosis, and on the risk of severe babesiosis in diagnosed cases, in dogs 6 months and older seen at a veterinary academic hospital in South Africa from 2013 through 2020. To estimate the effect of gonadectomy on the incidence rate of babesiosis diagnosis in dogs, we conducted a case-control study with incidence density sampling of dogs seen through the hospital's primary care service, adjusting for sex, age, breed category and weight. We identified 811 cases and selected 3244 time-matched controls. To estimate the effect of gonadectomy on disease severity in dogs with babesiosis, we conducted a retrospective cohort study among all dogs with a diagnosis of babesiosis (n=923), including these 811 cases and a further 112 referred to the hospital, also adjusting for sex, age, breed category and weight. Gonadectomy substantially reduced the incidence rate of babesiosis (total effect incidence rate ratio [IRR] 0.5; 95 % confidence interval [CI] 0.41-0.60) and the risk of severe babesiosis among diagnosed dogs (total effect risk ratio [RR] 0.72; 95 % CI 0.60-0.86). Tipping point sensitivity analysis shows that these effect estimates are robust to unmeasured confounding bias. There was no evidence for modification of the effect of gonadectomy by sex, with effect estimates qualitatively similar for males and females for both outcomes. Compared to females, males had a higher incidence rate of babesiosis (IRR 1.74; 95 % CI 1.49-2.04) and a higher risk of severe disease (RR 1.12; 95 % CI 0.98-1.28). In conclusion, our study shows a robust protective effect of gonadectomy on the incidence and severity of babesiosis in both male and female dogs 6 months of age and older, and contributes important evidence to the debate on the overall risks and benefits of gonadectomy to dogs in this population.