Temporal serum neurofilament light chain concentrations in sheep inoculated with the agent of classical scrapie.

OBJECTIVE: Neurofilament light chain (Nf-L) has been used to detect neuroaxonal damage in the brain caused by physical injury or disease. The purpose of this study was to determine if serum Nf-L could be used as a biomarker for pre-symptomatic detection of scrapie in sheep. METHODS: Four sheep with prion protein genotype AVQQ were intranasally inoculated with the classical scrapie strain x124. Blood was collected every 4 weeks until 44 weeks post-inoculation, at which point weekly collection commenced. Serum was analyzed using single molecule array (Quanterix SR-X) to evaluate Nf-L concentrations. RESULTS: Scrapie was confirmed in each sheep by testing homogenized brainstem at the level of the obex with a commercially available enzyme immunoassay. Increased serum Nf-L concentrations were identified above the determined cutoff during the last tenth of the respective incubation period for each sheep. Throughout the time course study, PrPSc accumulation was not detected antemortem by immunohistochemistry in rectal tissue at any timepoint for any sheep. RT-QuIC results were inconsistently positive throughout the timepoints tested for each sheep; however, each sheep had at least one timepoint detected positive. When assessing serum Nf-L utility using receiver operator characteristic curves against different clinical parameters, such as asymptomatic and symptomatic (pruritus or neurologic signs), results showed that Nf-L was most useful at being an indicator of disease only late in disease progression when neurologic signs were present. CONCLUSION: Serum Nf-L concentrations in the cohort of sheep increased as disease progressed; however, serum Nf-L did not increase during the presymptomatic window. The levels increased substantially throughout the final 10% of the animals' scrapie incubation period when other clinical signs were present. Serum Nf-L is not a reliable biomarker for pre-clinical detection of scrapie.

Combining epidemiological and ecological methods to quantify social effects on Escherichia coli transmission.

Enteric microparasites like Escherichia coli use multiple transmission pathways to propagate within and between host populations. Characterizing the relative transmission risk attributable to host social relationships and direct physical contact between individuals is paramount for understanding how microparasites like E. coli spread within affected communities and estimating colonization rates. To measure these effects, we carried out commensal E. coli transmission experiments in two cattle (Bos taurus) herds, wherein all individuals were equipped with real-time location tracking devices. Following transmission experiments in this model system, we derived temporally dynamic social and contact networks from location data. Estimated social affiliations and dyadic contact frequencies during transmission experiments informed pairwise accelerated failure time models that we used to quantify effects of these sociobehavioural variables on weekly E. coli colonization risk in these populations. We found that sociobehavioural variables alone were ultimately poor predictors of E. coli colonization in feedlot cattle, but can have significant effects on colonization hazard rates (p ≤ 0.05). We show, however, that observed effects were not consistent between similar populations. This work demonstrates that transmission experiments can be combined with real-time location data collection and processing procedures to create an effective framework for quantifying sociobehavioural effects on microparasite transmission.