High-Fidelity Point-of-Care Diagnostic Test for Periprosthetic Joint Infection: Commentary on an article by Thorsten Gehrke, MD, et al.
The lack of high-sensitivity, high-specificity laboratory tests for periprosthetic joint infection has historically resulted in ambiguous diagnoses for a large percentage of arthroplasty cases with a clinical suspicion of infection. In particular, this has been the case when specimens sent for microbial cultures did not support growth of pathogenic bacteria. This lack of an accurate diagnostic test forced the orthopaedic surgeon to rely largely or wholly on his or her clinical judgement. Thus, any rapid, accurate, molecular diagnostic test or biomarker assay would provide a substantive improvement over the current Musculoskeletal Infection Society (MSIS) guidelines for diagnosing periprosthetic joint infection1, and the development of an accurate point-of-care test would be truly transformative.
Recently, an immunoassay for the human alpha defensin protein has been developed as a biomarker for periprosthetic joint infection2, and testing of clinical samples has been performed in clinical laboratories using a moderately complex enzyme-linked immunosorbent assay (ELISA)-based method. Alpha defensin is a human host protein that is secreted by both activated neutrophils and, to a lesser extent, macrophages, as part of the innate immune system that provides a primary response to bacterial infection prior to the development of specific adaptive immune responses. On the basis of structural arguments, it is thought that the defensins form pores in the membranes of the bacteria, leading to loss of integrity; they are broadly effective against both gram-positive and gram-negative pathogens. A meta-analysis of 6 published studies examining the alpha defensin immunoassay using the first-generation ELISA-based method produced findings of near unity3 when compared with the MSIS gold standard, firmly establishing alpha defensin as an excellent biomarker for periprosthetic joint infection.
In this article, Gehrke et al. report on a second-generation commercial immunoassay for alpha defensin, the Synovasure Alpha Defensin Test, which utilizes (presumably) the same antibodies that were validated in the first-generation alpha defensin ELISA diagnostic test. In the current case, the Synovasure Alpha Defensin Test has been reformatted into a lateral flow format (analogous to an over-the-counter pregnancy test) that provides practitioners with a point-of-care, low-complexity assay that can provide real-time results while the patient is in the examining room or the operating room. Gehrke et al. demonstrate that this point-of-care assay has excellent sensitivity (92.1%) and superb specificity (100%) for the diagnosis of periprosthetic joint infection when compared with the MSIS gold standard.
The adoption of such a test could reduce the number of patient visits as the physician does not need to wait for results to come back from the laboratory to make a diagnosis if the test is performed on aspirated synovial fluid in the clinic. Moreover, the test has the potential to be easily integrated into multiple decision points during treatment, for example, aspiration prior to reimplantation during 2-stage revision or in the operating room during a primary revision surgical procedure.