Transmissible spongiform encephalopathy in goats: is PrP rapid test sensitivity affected by genotype?

Abstract

Transmissible spongiform encephalopathy (TSE) surveillance in goats relies on tests initially approved for cattle, subsequently assessed for sheep, and approval extrapolated for use in “small ruminants.” The current EU-approved immunodetection tests employ antibodies against various epitopes of the prion protein PrPSc, which is encoded by the host PRNP gene. The caprine PRNP gene is polymorphic, mostly at codons different from the ovine PRNP. The EU goat population is much more heterogeneous than the sheep population, with more PRNP-related polymorphisms, and with marked breed-related differences. The ability of the current tests to detect disease-specific PrPSc generated against these different genetic backgrounds is currently assumed, rather than proven. We examined whether common polymorphisms within the goat PRNP gene might have any adverse effect on the relative performance of EU-approved rapid tests. The sample panel comprised goats from the UK, Cyprus, France, and Italy, with either experimental or naturally acquired scrapie at both the preclinical and/or unknown and clinical stages of disease. Test sensitivity was significantly lower and more variable when compared using samples from animals that were preclinical or of unknown status. However, all of the rapid tests included in our study were able to correctly identify all samples from animals in the clinical stages of disease, apart from samples from animals polymorphic for serine or aspartic acid at codon 146, in which the performance of the Bio-Rad tests was profoundly affected. Our data show that some polymorphisms may adversely affect one test and not another, as well as underline the dangers of extrapolating from other species.

The Scrapie Prevalence in a Goat Herd Is Underestimated by Using a Rapid Diagnostic Test

“…A recent study in goats demonstrated that rapid screening tests performed well in clinically affected animals but were less sensitive in the pre-clinical phase, which was dependent on PRNP polymorphisms. In particular, the presence of the M 142 allele appeared to compromise to some extent the sensitivity of the Bio-Rad screening tests (Simmons et al, 2020).…”

“…To assess whether false negative results in the screening ELISA test were associated with higher optical density (OD) values than true negative results, OD values for each sample were divided by the cut-off specified for each test run to calculate an OD cut-off ratio (multiplied by 100). The ratios were grouped by PRNP genotype at codon 142 based on recent findings that PRNP polymorphisms may affect test sensitivity in goats (Simmons et al, 2020), and the data compared by non-parametric Mann-Whitney U-test. This test was also used to compare the ages of goats with a false negative and true negative ELISA result, grouped by genotype at codon 142.…”

Evaluation of the application of the Czech Republic to be recognised as having a negligible risk of classical scrapie

“…A further confounding issue when considering diagnostic screening test performance in goats is that the formal test evaluations that were undertaken in respect of small ruminant testing were conducted using only sheep scrapie samples. It has been shown subsequently that not all tests perform equally in all genotypes of goats (Papasavva‐Stylianou et al., 2017 ; Konold et al., 2020 ; Simmons et al., 2020 ). Not all caprine PRNP polymorphisms are synonymous with ovine ones, and some caprine polymorphisms coincide with particular diagnostic antibody‐binding sites, reducing the sensitivity of individual tests in certain animals.…”

Annual Report of the Scientific Network on BSE‐TSE 2020

“…John Spiropoulos, senior veterinary pathologist of the Animal and Plant Health Agency (APHA) (UK), invited speaker, presented the results of two recently published scientific articles of interest, of which he is co-author: 'Transmissible spongiform encephalopathy in goats: is PrP rapid test sensitivity affected by genotype?' (Simmons et al, 2020), and 'The Scrapie Prevalence in a Goat Herd Is Underestimated by Using a Rapid Diagnostic Test' (Konold et al, 2020). The sensitivity of the Rapid test for the detection of TSE in goats (scrapie and BSE) is not 100%, and is influenced by the polymorphisms in certain codons which may alter epitope binding, the rapid test chosen, sampling issues and other still unknown factors.…”