Diagnosis of human brucellosis

Dr J Rossouw and A/Prof John Frean

Special Bacterial Pathogens Reference Laboratory

Centre for Emerging Zoonotic and Parasitic Diseases

National Institute for Communicable Diseases, Johannesburg

Laboratory diagnosis of human Brucella infection is complicated and none of the currently available diagnostic tools can be used on its own to reliably detect the pathogen.  Definitive laboratory diagnosis of human brucellosis is based on isolation of the bacteria from clinical samples (blood, bone marrow or other tissues).  However, cultures give a low yield as Brucella is fastidious and the bacterial load in clinical samples varies widely.  The isolation of Brucella is highly dependent on the stage of disease (acute versus chronic), antibiotic treatment, availability of appropriate clinical samples, and the culturing method.  Advances in automated blood culture systems have decreased the culture time and increased the recovery rate from normally-sterile body fluids. In recent years, matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS) has been shown to be an effective tool to identify Brucella spp. directly, from both culture plates and blood culture bottles. However, it is not routinely used because of limited availability.

Serological testing is preferred in routine clinical practice as it is non-hazardous, faster and more sensitive than bacterial culture. Many serological assays are available for the diagnosis of human brucellosis. However, interpretation of these assays is often difficult because: i) many patients are seronegative in the acute phase of the disease, which necessitates serological testing of paired sera or performing more than one serological test; ii) a high proportion of the population in endemic regions may have persistent antibody titres due to exposure to Brucella; iii) antibodies can remain detectable despite successful therapy; and iv) cross-reaction with Gram-negative bacteria (e.g. Salmonella, Yersinia) may occur.  Serology results should be interpreted in combination with clinical signs and symptoms.

Various polymerase chain reaction (PCR) molecular assays have been developed for the diagnosis of human brucellosis from pure cultures and clinical specimens (i.e. serum, whole blood, urine samples, various tissues, etc.). PCR is more sensitive than blood cultures and more specific than serological tests.