Abstract
The diagnosis of brucellosis encompasses multiple scenarios, methodologies, requirements, objectives, hosts and pathogen species. Definitive diagnosis is only possible via isolation and identification of Brucella but this presents challenges due to imperfect sensitivity, biorisk, capability and cost. Other approaches are needed to navigate these issues including measurement of the host immune response and detection of DNA. Alongside epidemiological information the results from such tests can inform a suitable risk-based diagnostic interpretation and response. Despite the challenges of brucellosis control the diagnostic element is in many cases strong. For example, the Brucella sLPS is a gift to the diagnostician. It is abundant on the cell surface, is robust, multivalent, amphiphilic, T-independent and subject to the adaptive immune response and a single type may be universally applied for detection of infection with [nearly] all smooth stains. It underpins all primary serological assays, the appropriate implementation and interpretation of which should be a primary objective of any testing system. Diagnostic weaknesses include the non-universal attainment of good quality diagnostic antigen, an issue compounded by costs and the biological risks. Induction of false positive serological reactions due to vaccination or infection with cross reactive organisms occur - althoughtheir occurrence and significance varies considerably by circumstance. Measurement of the cellular immune response may assist diagnosis but access to the required reagents is poor. At the molecular level, recombinant and synthetic approaches offer some basis for insight and solution. Recombinant skin test antigen is being developed for bovine tuberculosis. Data using synthetic OPS based oligosaccharides suggests that antigen presentation impacts upon antibody induction - information which may provide new options for resolution of FPSRs. An alternative strategy is the application of other abundant cell surface antigens. The atypical properties of the rLPS core make this an attractive target. Select excipients appear to improve its diagnostic potential with respect to infection with smooth and with rough strains. At the global level the prevalence of disease in humans and animals remains poorly understood. Are limitations in existing diagnostic tools contributory to this knowledge gap? If so, what more can be done and how can this be achieved?
