Bayesian evaluation of temporal changes in sensitivity and specificity
of three serological tests for multiple circulating strains of rabbit
haemorrhagic disease virus
Abstract
Competition and indirect ELISAs are currently being used to monitor
rabbit hemorrhagic disease viruses (RHDV1 and RHDV2) in rabbits
worldwide. Temporal changes in the sensitivity (Se) and specificity (Sp)
of assays were investigated using Bayesian Latent Class models (BCLM) in
the Australian wild rabbit population where both viruses circulate
simultaneously and a long-term serological dataset exists. When cELISA1
was compared to IgG1 ELISA, the Se of cELISA1 improved while the Sp of
IgG1 ELISA declined over the 2011-2021. This corresponded with a decline
in the true RHDV1 prevalence in 2018-21, suggesting that a large
proportion of RHDV1 exposed rabbits survived the introduction and
dominance of RHDV2 up to approximately 2017/2018, after which they died
and were not replaced. The Se and Sp estimates for 2014-15 for both
cELISA1 and IgG1 ELISA, and the true prevalence when analysing all three
tests together were similar to those obtained from the analysis of
cELISA1/IgG1. The same was also true for the Se and Sp of cELISA2 and
IgG1 estimates from 2018 onwards. This suggests that RHDV1 was the
dominant infection status in 2014-15, but RHDV2 was the dominant
infection status in 2018-2021. Further, the increase in Se of cELISA2
and the low Sp of IgG1 ELISA in the cELISA2/IgG1 ELISA analysis,
compared to the Se of cELISA2 and Sp of IgG1 ELISA when analysing all
three tests together suggests that the underlying infection status was
more influenced by RHDV2 and that the higher Se of IgG1 ELISA is due to
cross-reaction of RHDV2 antibodies on IgG1 ELISA. The true prevalence
data suggests that RHDV2 exposure peaked in 2017. Our findings show that
test characteristics changed in response to the changing virus
prevalences over time. IgG1 ELISA currently has a high Se, should be
used to monitor both viruses and will perform better than both cELISAs.