Establishment of a Diagnosis
Many different decision makers rely on diagnostic test results, but often the decision makers are farmers, who wish to make inferences about individual animals or their herd/flock.
Veterinary authorities can also use diagnostic tests to classify individual animals, herds/ flocks or even entire regions as infected or contaminated. The reason for this classification is to enable decision making in relation to a specific goal. The goals may differ from one decision maker to another, but they are usually directed by the purpose of the efforts: why does the decision maker wish to establish a diagnosis? Ultimately, a test result should lead to an action. Actions might include: (i) doing nothing, e.g. because the tested subject is considered to be non-infected or unlikely to contribute to transmission; (ii) isolating the subject from susceptible subjects, e.g. to stop transmission; (iii) culling to remove the infected or infectious subject fully from the population; (iv) removing a subject from the food chain if the subject is considered a public health hazard; (v) treating the subject; (vi) re-testing if the classification of the subject is not clear. Other actions can also be defined, for example for research purposes, or because herds or flocks with a superior infection status may attract a financialTable 20.1. Overview of aspects relevant in a diagnostic test strategy.
| Aspect | Relevance |
| Why | Purpose of testing and efforts |
| Who | Decision makers Stakeholders Advisors |
| What | Adverse effects/outcomes (pathogenesis) Analytes (and their concentration) |
| How | Sample matrix Sampling Sampling frequency |
| Interpretation | Effect of bias Utility • Interpretation • Application • Uncertainty • Decision making |
premium for their products.
The purpose and the associated actions usually define what the test should be able to detect and how it should be interpreted. A purpose is established to reduce adverse outcomes through these actions.MAP infections have a long and variable incubation period. During this period, a number of outcomes can occur, such as: (i) establishment of the infection; (ii) faecal shedding of MAP in sufficient quantities to result in transmission to susceptible herd-mates; (iii) bacteraemia, which can lead to the shedding of MAP in milk or the transfer of MAP to a fetus in utero; and (iv) decreased milk production, weight loss, diarrhoea or death. These outcomes are of varying interest to different decision makers (politicians, farmers, etc.) and in various settings (no reported occurrence, low prevalence or high prevalence). Consequently, the reason for using a diagnostic test will vary as well. The following are examples of purposes for testing: (i) certification, i.e. to certify a herd, animal or region free of MAP infection; (ii) to establish the prevalence, i.e. the proportion of MAP-infected animals in a target population to determine whether intervention should be instated; (iii) reducing transmission to prevent future MAP infections; (iv) to increase production parameters (e.g. milk and beef); (v) to increase animal welfare, e.g. to avoid animals suffering from diarrhoea, etc. These distinct purposes will serve as the background for further discussion of immunebased diagnosis and the actions that should follow the diagnosis. In addition to these different aims of testing, the target conditions can range from: (i) non-infected (for certification);
(ii) MAP-infected (for prevalence estimation);
(iii) MAP-infectious (for reduced transmission); and (iv) MAP-affected (for increased production parameters and animal welfare). The term ‘MAP-affected’ is preferentially used over ‘clinical disease’ because of the variable definition and use of the term ‘clinical’ in the literature and among decision makers.
Once the purpose and target condition are established, we must identify the analytes on which the diagnostic test is based. To identify relevant analytes, we require an insight into the pathogenesis of infection and disease. The commonly detected analytes are MAP, MAP DNA or MAP-specific antibodies, with the latter being of primary relevance in this chapter. These are used, because we have sufficient information about their significance in the pathogenesis. Other analytes include indicators of cell-mediated immunity such as interferongamma (IFN-γ). However, the relation between cell-mediated immune responses and the outcomes listed above is still insufficiently described to be used in decision making. In order to detect the analytes, they must of course be present, but more importantly, we must be able to infer what their presence (or absence) means in relation to the purpose and the target condition. This often presents a challenge due to the many potential adverse outcomes, target conditions and associated purposes. Therefore, we need to be precise in the terminology used when characterizing how well the detection of the analytes relates to the purpose and target condition.
20.3