Diagnosis of brucellosis: Combining tests to improve performance

Introduction: Brucellosis, a zoonotic infectious disease caused by bacteria of the genus Brucella, remains a significant global health concern in many parts of the world. Traditional diagnostic methods, including serological tests, suffer from limitations, including low sensibility and high false-positive rates, emphasizing the need for improved diagnostic strategies. In this study, we aimed to optimize diagnostic accuracy by reevaluating serological tests and exploring novel diagnostic algorithms. Methods: A retrospective observational study was conducted using sera collected between June 2012 and June 2023 at the French National Reference Center for Brucella. Various serological tests, including Rose Bengal plate test (RBT), standard agglutination test (SAT), Brucellacapt, and ELISA for IgM and IgG, were performed. Different diagnostic algorithms were evaluated, combining RBT with SAT, Brucellacapt, and ELISA to enhance the performance of diagnostic tests. Results: Among 3587 sera analyzed, 148 were confirmed cases of human brucellosis. Individual serological tests exhibited good sensitivity and specificity but lacked diagnostic accuracy. However, combining RBT with SAT or Brucellacapt significantly improved diagnostic performance, with reduced false positives. The most promising results were observed when an algorithm was built combining RBT, Brucellacapt, and ELISA for IgM and IgG (a score value of 0.5 with 90.5% for sensitivity, 99.7% for specificity, 92.4% for PPV, and 99.6% for NPV). Conclusions: Serological tests remain crucial for brucellosis diagnosis, but their limitations necessitate innovative diagnostic approaches. Combining multiple serological tests in diagnostic algorithms shows promise in improving diagnostic accuracy. Efforts to refine diagnostic, strengthen surveillance, and raise awareness are essential for effective brucellosis control, particularly in resource-limited settings. Author summary: Brucellosis is a zoonotic infectious disease caused by bacteria of the genus Brucella. This disease remains a significant global health concern in many parts of the world. Traditional diagnostic methods include serological tests. However, these tests have major limitations due to their low sensibility and high false-positive rates. This poses a significant challenge in clinical practice, emphasizing the necessity for careful interpretation of test results and the development of more specific diagnostic tools. In this study, we assess the utility of traditional and easily accessible serological tests. Instead of using them individually, we decided to integrate the results of these multiple testing methods. We highlight the value of combining serological results into an algorithm to enhance the diagnosis of brucellosis and achieve greater overall accuracy in diagnosis. Efforts to streamline diagnostic, bolster surveillance, and increase awareness are essential for controlling brucellosis, particularly in resource-limited settings with a high disease burden.