Laboratory Diagnosis of Human Brucellosis Pablo Yagupsky, a Pilar Morata, b,d Juan D. Colmenero c,d a Clinical Microbiology Laboratory, Soroka University Medical Center, Ben-Gurion University of the Negev, Beer-Sheva, Israel b Biochemistry and Molecular Biology Department, Faculty of Medicine, University of Málaga, Málaga, Spain c Infectious Diseases Service, University Regional Hospital, Málaga, Spain d IBIMA, Málaga, Spain SUMMARY ........................................................................................ 2 INTRODUCTION .................................................................................. 2 The Global Challenge of Human Brucellosis and Its Diagnosis ............................ 3 Diagnosing Human Brucellosis: Culture, Serology, and NAATs ............................. 4 CULTURE DETECTION OF BRUCELLAE ......................................................... 4 Blood Cultures ................................................................................. 4 Dynamics of Brucella bacteremia ........................................................... 5 Assessing the performance of blood culture methods for the detection of brucellae . 5 Blood culture methods ...................................................................... 6 (i) Manual monophasic method .......................................................... 6 (ii) Manual biphasic methods............................................................. 6 (iii) Lysis-based blood cultures ........................................................... 7 (iv) Blood clot cultures .................................................................... 9 (v) Automated blood culture systems ................................................... 9 (vi) Is the traditional recommendation of prolonged incubation of vials still valid? .................................................................................. 14 (vii) Which of the current blood culture systems is superior for recovering brucellae? ............................................................................. 14 (viii) Blood versus bone marrow cultures as the diagnostic gold standard ......... 15 Isolation of Brucellae from Specimens Other than Blood .................................. 16 Traditional culture methods ............................................................... 16 Use of blood culture methods for culturing other biological specimens .............. 16 From Detection to Identification ............................................................. 17 Conventional methods ..................................................................... 17 MALDI-TOF technology .................................................................... 19 Brucella Cultures and Laboratory Safety .................................................... 19 Conclusions ................................................................................... 21 SERODIAGNOSIS OF HUMAN BRUCELLOSIS ................................................ 21 Serological Diagnosis of Human Brucellosis: Imperfect but Indispensable .............. 21 Brucella Antigens for Serodiagnosis: LPS and Cytosol Proteins ........................... 22 Humoral Immune Response in Human Brucellosis ........................................ 23 Outdated and Obsolete Diagnostic Tests .................................................. 24 Serological Tests That Target Brucellar S-LPS ............................................... 24 RBT .......................................................................................... 24 SAT .......................................................................................... 25 (i) Microagglutination test............................................................... 26 2-ME test .................................................................................... 26 Coombs antiglobulin agglutination test .................................................. 26 Brucella Coombs gel test................................................................... 27 CF test ....................................................................................... 27 Immunocapture agglutination test........................................................ 27 IgG avidity ELISA ........................................................................... 28 Serological Tests That Target Cytosolic Proteins............................................ 28 ELISA......................................................................................... 28 Novel Serodiagnostic Tests ................................................................... 29 TR-FRET assay ............................................................................... 29 FPA .......................................................................................... 29 Rapid Point-of-Care Tests .................................................................... 29 Dipstick assay ............................................................................... 30 LFA .......................................................................................... 30 (continued) Citation Yagupsky P, Morata P, Colmenero JD. 2019. Laboratory diagnosis of human brucellosis. Clin Microbiol Rev 33:e00073-19. https://doi.org/10.1128/CMR.00073-19. Copyright © 2019 American Society for Microbiology. All Rights Reserved. Address correspondence to Pablo Yagupsky, [email protected]. Published REVIEW crossm January 2020 Volume 33 Issue 1 e00073-19 cmr.asm.org 1 Clinical Microbiology Reviews 13 November 2019 Downloaded from https://journals.asm.org/journal/cmr on 28 May 2023 by 171.243.67.90.
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