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Multi-event capture-recapture models estimate the diagnostic performance of serological tests for myxoma and rabbit haemorrhagic disease viruses in the absence of reference samples.

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Estimation of the diagnostic performance of serological tests often relies on another test assumed as reference or on samples of known infection status, yet both are seldom available for emerging… Click to show full abstract

Estimation of the diagnostic performance of serological tests often relies on another test assumed as reference or on samples of known infection status, yet both are seldom available for emerging pathogens in wildlife. Longitudinal disease serological data can be analysed through multi-event capture-mark-recapture (MECMR) models accounting for the uncertainty in state assignment, allowing to estimate epidemiological parameters such as incidence and mortality. We hypothesised that, by estimating the uncertainty in state assignment, MECMR models estimate the diagnostic performance of serological tests for rabbit haemorrhagic disease virus (RHDV) and myxoma virus (MYXV). We evaluated this hypothesis on longitudinal serological data of three tests RHDV and one test for MYXV, in two populations of the European rabbit (Oryctolagus cuniculus algirus). First, we selected the optimal cut-off threshold for each test using finite mixture models, a reference method not relying on reference tests or samples. Second, we used MECMR models to compare the diagnostic sensitivity (Se) and specificity (Sp) of the three tests for RHDV. Third, we compared the estimates of diagnostic performance by MECMR and finite mixture models, across a range of cut-off values. The MECMR models showed that the RHDV test employing GI.2 antigens (Se: 100%) outperformed two tests employing GI.1 antigens (Se: 21.7 ± 8.6% and 8.7 ± 5.9%). At their selected cut-offs (2.0 for RHDV GI.2 and 2.4 for MYXV), the estimates of the Se and Sp were concordant between MECMR and finite mixture models. Over the duration of the study (May 2018 to September 2020), the monthly survival of European rabbits seropositive for MYXV was significantly higher than that of seronegative rabbits (82.7 ± 4.9% vs 61.5 ± 12.7%) at the non-fenced site. We conclude that MECMR models can reliably estimate the diagnostic performance of serological tests for RHDV and MYXV in the European rabbit. This conclusion could extend to other diagnostic tests and host-pathogen systems. Longitudinal disease surveillance data analysed through MECMR models allow to validate diagnostic tests for emerging pathogens in novel host species, while simultaneously estimating epidemiological parameters. This article is protected by copyright. All rights reserved.

Keywords: mecmr models; serological tests; reference; performance serological; diagnostic performance; performance

Journal Title: Transboundary and emerging diseases
Year Published: 2022

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