The persistent worldwide prevalence of human brucellosis causes serious public health concerns and economic loss to communities. The multisystem involvement and the protean and unusual clinical presentations of the disease pose significant diagnostic challenges. The clinical features are non-specific and can overlap with a wide spectrum of other infectious and non-infectious diseases, leading to brucellosis being labelled the 'disease of mistakes'. Protracted chronicity and serious complications can result and mislead physicians onto a path of costly laboratory and radiological investigations. To reach a diagnosis clinicians must use a wide range of non-specific routine haematological and biochemical tests in addition to Brucella-specific assays. The latter are microbiological (culture), serological (e.g. slide or tube agglutination, Coombs test, immunocapture agglutination, Brucellacapt, immunochromatographic lateral flow, enzyme-linked immunosorbent assays and the indirect fluorescent antibody test) and molecular (e.g. polymerase chain reaction (PCR) and real-time PCR). Each of these tests has advantages and limitations, and thus requires careful interpretation. Since brucellosis can have several presentations and phases (acute, subacute, chronic, relapsed, active and inactive), the search for reliable, discriminatory diagnostic and prognostic markers, especially for monitoring disease evolution, are ongoing. Although much progress has been made, further challenges remain to the accurate diagnosis of this historic but still common global zoonotic disease.
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