Combining analytical approaches and multiple information sources to improve interpretation of diagnostic test results for tuberculosis in wild meerkats

Patterson, Stuart; Clarke, Charlene; Clutton Brock, Tim; Miller, Michele; Parsons, Sven; Pfeiffer, Dirk; Vergne, Timothee; Drewe, Julian

Abstract

Diagnostic tests are used to classify individual animals’ infection statuses. However, validating test performance in wild animals without gold standard tests is extremely challenging, and the issue is further complicated in chronic conditions where measured immune parameters vary over time. Here, we demonstrate the value of combining evidence from different diagnostic approaches to aid interpretation in the absence of gold standards, large sample sizes, and controlled environments. Over a two-year period, we sampled 166 free-living meerkats (Suricata suricatta) longitudinally for tuberculosis, using three ante-mortem diagnostic tests based on mycobacterial culture, and antigen-specific humoral and cell-mediated immune responses, interpreting results both independently and in combination. Post-mortem cultures confirmed Mycobacterium suricattae infection in 26 animals, 59% of which were test-positive on a parallel test interpretation (PTI) of the three ante-mortem diagnostic assays (95% confidence interval: 37-79%). A similar ability to detect infection, 65.7% (95% credible interval: 42.7-84.7%), was estimated using a Bayesian approach to examine PTI. Strong evidence was found of a positive association between PTI and survival time, with a positive result nearly doubling the hazard of death (Hazard Ratio 1.75, CI: 1.14-2.67, p=0.01), thus demonstrating that these test results are related to disease outcomes. For individual tests, small sample sizes led to wide confidence intervals, but replication of conclusions, using different methods, increased our confidence in these results. This study demonstrates that combining multiple methodologies to evaluate diagnostic tests in free-ranging wildlife populations can be a useful approach for exploiting such valuable datasets.

Citation

Patterson, S., Clarke, C., Clutton Brock, T., Miller, M., Parsons, S., Pfeiffer, D., …Drewe, J. (2021). Combining analytical approaches and multiple information sources to improve interpretation of diagnostic test results for tuberculosis in wild meerkats. Animals,

• Journal Article Type: Article
• Acceptance Date: Nov 29, 2021
• Publication Date: Dec 4, 2021
• Deposit Date: Oct 25, 2021
• Publicly Available Date: Jan 14, 2022
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Public URL: https://rvc-repository.worktribe.com/output/1552050