Modelling diagnostics for Echinococcus granulosus surveillance in sheep using Latent Class Analysis: Argentina as a case study

Abstract

Echinococcus granulosus sensu lato is a globally prevalent zoonotic parasitic cestode leading to cystic echinococcosis (CE) in both humans and sheep with both medical and financial impacts, whose reduction requires the application of a One Health approach to its control. Regarding the animal health component of this approach, lack of accurate and practical diagnostics in livestock impedes the assessment of disease burden and the implementation and evaluation of control strategies. We use of a Bayesian Latent Class Analysis (LCA) model to estimate ovine CE prevalence in sheep samples from the Río Negro province of Argentina accounting for uncertainty in the diagnostics. We use model outputs to evaluate the performance of a novel recombinant B8/2 antigen B subunit (rEgAgB8/2) indirect enzyme-linked immunosorbent assay (ELISA) for detecting E. granulosus in sheep. Necropsy (as a partial gold standard), western blot (WB) and ELISA diagnostic data were collected from 79 sheep within two Río Negro slaughterhouses, and used to estimate individual infection status (assigned as a latent variable within the model). Using the model outputs, the performance of the novel ELISA at both individual and flock levels was evaluated, respectively, using a receiver operating characteristic (ROC) curve, and simulating a range of sample sizes and prevalence levels within hypothetical flocks. The estimated (mean) prevalence of ovine CE was 27.5% (95%Bayesian credible interval (95%BCI): 13.8%–58.9%) within the sample population. At the individual level, the ELISA had a mean sensitivity and specificity of 55% (95%BCI: 46%–68%) and 68% (95%BCI: 63%–92%), respectively, at an optimal optical density (OD) threshold of 0.378. At the flock level, the ELISA had an 80% probability of correctly classifying infection at an optimal cut-off threshold of 0.496. These results suggest that the novel ELISA could play a useful role as a flock-level diagnostic for CE surveillance in the region, supplementing surveillance activities in the human population and thus strengthening a One Health approach. Importantly, selection of ELISA cut-off threshold values must be tailored according to the epidemiological situation.

Immunodiagnosis of cystic echinococcosis in livestock: Development and validation dataset of an ELISA test using a recombinant B8/2 subunit of Echinococcus granulosus sensu lato

“…Usefulness for CE control and surveillance: The rEgAgB8/2 indirect ELISA for ovine CE developed and reported here would be particularly useful for flock diagnosis in control and surveillance programmes [1] .…”

“…Prada, Modelling diagnostics for Echinococcus granulosus surveillance in sheep using Latent Class Analysis: Argentina as a case study, One Health. 14 (2021) 100359, 10.1016/j.onehlt.2021.100359 [1] .…”

“… Novelty: The rEgAgB8/2 antigen had been demonstrated to be an appropriate antigen for serological diagnosis of human CE [2] , but not previously applied for CE diagnosis in sheep. Programmatic applications: Usefulness for CE control and surveillance: The rEgAgB8/2 indirect ELISA for ovine CE developed and reported here would be particularly useful for flock diagnosis in control and surveillance programmes [1] . Prevention of CE infection introduction or re-introduction: The ELISA test described here could be used in serological surveys to detect cyst-bearing animals from endemic areas in transit to CE-free areas to minimise propagation of E. granulosus s.l.…”

“…Determination of its repeatability and reproducibility will be essential for its validation and adoption in CE control and surveillance programmes. Epidemiological applications: Quantification of ovine CE prevalence: Data generated by applying the ELISA test presented here can be used in conjunction with other diagnostics to improve estimates of ovine CE prevalence [1] as necropsy is only a partial gold standard which can miss early/small-size cyst infections [3] . Its use for flock-level diagnosis can help improve CE surveillance [4] .…”

“…Quantification of ovine CE prevalence: Data generated by applying the ELISA test presented here can be used in conjunction with other diagnostics to improve estimates of ovine CE prevalence [1] as necropsy is only a partial gold standard which can miss early/small-size cyst infections [3] . Its use for flock-level diagnosis can help improve CE surveillance [4] .…”