Bartonella henselae: A challenging diagnosis with a bright future

Bartonella henselae is a fastidious, facultative intracellular, Gram-negative bacterium that causes Cat Scratch Disease (CSD), a zoonosis in which domestic cats are the primary reservoir and humans as incidental hosts. While CSD is often self-limiting, it can lead to severe systemic complications, particularly in immunocompromised individuals. Diagnosing Ba. henselae infection remains challenging, as conventional methods — including culture, Enzyme -Linked Immunosorbent Assay (ELISA), Indirect Immunofluorescence Assay (IFA) and Polymerase Chain Reaction (PCR) — suffer from low sensitivity, cross-reactivity and lack of standardization. Serological assays are widely used but frequently exhibit cross-reactivity with antigenically related pathogens such as Chlamydia pneumoniae and Coxiella burnetii, limiting specificity. To overcome these issues, the identification of specific antigenic determinants has become a key focus. Recombinant protein-based assays have emerged as promising tools, offering improved specificity, reduced cross-reactivity and greater reproducibility compared to traditional whole-cell antigen approaches. This review critically assesses current diagnostic techniques for B. henselae, highlights their limitations and explores innovative strategies centered on the use of recombinant antigens for enhanced serological diagnosis.