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Combining Analytical Approaches and Multiple Sources of Information to Improve Interpretation of Diagnostic Test Results for Tuberculosis in Wild Meerkats.

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 268 free-living meerkats (Suricata suricatta) longitudinally for Mycobacterium suricattae (a causative agent of 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 M. suricattae infection in 22 animals, which had prior ante-mortem information, 59% (13/22) 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 for a near doubling of the hazard of death (Hazard Ratio 1.75, CI: 1.14-2.67, p = 0.01), associated with a positive PTI result, 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.

SUBMITTER: Patterson SJ

PROVIDER: S-EPMC8698085 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Tuberculosis (TB) is an important and widespread disease of wildlife, livestock and humans world-wide, but long-term empirical datasets describing this condition are rare. A population of meerkats (Suricata suricatta) in South Africa's Kalahari Desert have been diagnosed with Mycobacterium suricattae, a novel strain of TB, causing fatal disease in this group-living species. This study aimed to find characteristics associated with clinical TB in meerkats. These characteristics could subsequently be used to identify 'at-risk' animals within a population, and target these individuals for control measures. We conducted a retrospective study based on a unique, long-term life-history dataset of over 2000 individually identified animals covering a 14-year period after the first confirmatory diagnosis of TB in this population in 2001. Individual- and group-level risk factors were analysed using time-dependent Cox regression to examine their potential influence on the time to development of end-stage TB. Cases of disease involved 144 individuals in 27 of 73 social groups, across 12 of 14 years (an incidence rate of 3·78 cases/100 study years). At the individual level, increasing age had the greatest effect on risk of disease with a hazard ratio of 4·70 (95% CI: 1·92-11·53, P < 0·01) for meerkats aged 24-48 months, and a hazard ratio of 9·36 (3·34-26·25, P < 0·001) for animals aged over 48 months (both age categories compared with animals aged below 24 months). Previous group history of TB increased the hazard by a factor of 4·29 (2·00-9·17, P < 0·01), and an interaction was found between this variable and age. At a group level, immigrations of new group members in the previous year increased hazard by a factor of 3·00 (1·23-7·34, P = 0·016). There was weaker evidence of an environmental effect with a hazard ratio for a low rainfall (<200 mm) year of 2·28 (0·91-5·72, P = 0·079). Our findings identify potential individual characteristics on which to base targeted control measures such as vaccination. Additional data on the dynamics of the infection status of individuals and how this changes over time would complement these findings by enhancing understanding of disease progression and transmission, and thus the implications of potential management measures.

Project description:BACKGROUND:The ability to recombine smaller units to produce infinite structures of higher-order phrases is unique to human language, yet evidence of animals to combine multiple acoustic units into meaningful combinations increases constantly. Despite increasing evidence for meaningful call combinations across contexts, little attention has been paid to the potential role of temporal variation of call type composition in longer vocal sequences in conveying information about subtle changes in the environment or individual differences. Here, we investigated the composition and information content of sentinel call sequences in meerkats (Suricata suricatta). While being on sentinel guard, a coordinated vigilance behaviour, meerkats produce long sequences composed of six distinct sentinel call types and alarm calls. We analysed recordings of sentinels to test if the order of the call types is graded and whether they contain additional group-, individual-, age- or sex-specific vocal signatures. RESULTS:Our results confirmed that the six distinct types of sentinel calls in addition to alarm calls were produced in a highly graded way, likely referring to changes in the perceived predation risk. Transitions between call types one step up or down the a priory assumed gradation were over-represented, while transitions over two or three steps were significantly under-represented. Analysing sequence similarity within and between groups and individuals demonstrated that sequences composed of the most commonly emitted sentinel call types showed high within-individual consistency whereby adults and females had higher consistency scores than subadults and males respectively. CONCLUSIONS:We present a novel type of combinatoriality where the order of the call types contains temporary contextual information, and also relates to the identity of the caller. By combining different call types in a graded way over long periods, meerkats constantly convey meaningful information about subtle changes in the external environment, while at the same time the temporal pattern of the distinct call types contains stable information about caller identity. Our study demonstrates how complex animal call sequences can be described by simple rules, in this case gradation across acoustically distinct, but functionally related call types, combined with individual-specific call patterns.

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Combining Analytical Approaches and Multiple Sources of Information to Improve Interpretation of Diagnostic Test Results for Tuberculosis in Wild Meerkats.

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