Statistical models for the effect of age and maternal antibodies on the development of rabbit haemorrhagic disease in Australian wild rabbits

Abstract

Statistical models have been developed to explain the influence of age and maternal antibody on the outcome of rabbit haemorrhagic disease virus (RHDV) infection of Australian wild rabbit kittens in terms of survival, survival time in those that failed to survive, and pyrexia (temperature response, or fever). Similar models describing survival and survival time were derived by substituting mass for age, owing to their high correlation. The models were developed from data obtained following the inoculation of 78 kittens 5–11 weeks old born to does with varying levels of α-RHDV immunoglobulin (IgG) antibody as measured by enzyme-linked immunosorbent assay (ELISA). A significant correlation was found between survival and doe titre but not between survival and kitten titre. It was deduced that maternal antibody in kittens can fall below the level of detection in the ELISA but still be protective. The model describing the influence of age and doe titre had the form logit(SURVIVAL) = 5.98 – 0.944(AGE) + 0.000473(DOE TITRE), and showed, for example, that kittens born to seronegative does had a 50% probability of survival at about 6 weeks old and, with a doe titre of 10 240, a 50% probability of survival at about 11 weeks old. There was a significant influence of kitten titre on pyrexia, and the model developed had the form logit(TEMPERATURE RESPONSE) = 1.436 – 0.0531(KITTEN TITRE). The influence of age and maternal antibody on survival time was fitted using Cox proportional hazard models. A parametric regression gave rise to a final model of the form S(t | AGE, DOE TITRE) = exp[–(t/η_AGE)^1.7979], where η_AGE = exp[7.1838 – 0.2976(AGE) + 0.000227(DOE TITRE)]. The model showed that survival time decreased with age, but for each age category there was an increase in survival time with increasing doe titre. Kitten titre had only a marginally significant effect on seroconversion; there was no effect of kitten age or mass, or of doe titre. No kitten with a titre of 60 or more seroconverted.