Razonable, Raymund R.

Background: Diagnostic uncertainty caused by the low positive predictive value of HEV-specific IgM antibody (Ab) testing in a low-prevalence setting. We investigated the utility of a two-step HEV IgM Ab testing approach for diagnosing HEV infection. Methods: We retrospectively reviewed all adults who underwent HEV IgM Ab and/or HEV RNA testing from July 2013 through June 2023 at Mayo Clinic. Two-step HEV IgM testing involved initial testing using recomWell HEV IgM ELISA (Mikrogen, Neuried, Germany), with reflex to recomLine HEV IgM Strip (Mikrogen, Neuried, Germany) on all recomWell HEV IgM-reactive or IgM-equivocal specimens, as recomLine HEV IgM has higher specificity than recomWell HEV IgM but is more labor-intensive. Results: A total of 1640 patients had HEV IgM Ab or HEV RNA testing, including 1293 (79%) with only HEV IgM Ab testing, 213 (13%) with only HEV RNA testing, and 134 (8%) with both HEV IgM Ab and HEV RNA testing. Eighteen HEV infections were diagnosed with acute (N=16) and chronic (N=2) infections. Two-step IgM Ab testing did not identify 2 solid organ transplant recipients with chronic HEV infection. In acute HEV infection with HEV viremia, 3 out of 4 patients (2 solid organ transplant recipients and 1 patient with Guillain-Barre syndrome) were treated with ribavirin. Conclusions: A two-step HEV IgM Ab test may accurately diagnose acute HEV infection in immunocompetent persons. However, this approach fails to identify chronic HEV infection in immunocompromised individuals who need HEV RNA testing to establish the diagnosis.

Introduction: The pathogenesis and outcome of cytomegalovirus (CMV) infection after solid organ transplantation (SOT) reflects the interplay between viral replication and CMV-specific immunity. Despite advances in its diagnosis and treatment, CMV continues to cause significant morbidity after SOT. Since CMV is an opportunistic pathogen that occurs as a result of impaired pathogen-specific immunity, laboratory assays that measure CMV-specific immune responses may be useful in assisting clinicians in its management. Methods and Results: The author summarizes the evolving and emerging data on the clinical utility of assays that quantify cell-mediated immune responses to CMV in SOT recipients. The majority of publications are observational studies that demonstrate that a lack or deficiency in CMV-specific cell-mediated immunity is correlated with a heightened risk of primary, reactivation, or recurrent CMV after transplantation. A few prospective interventional studies have utilized CMV-specific cell-mediated immune assays in guiding the duration of antiviral prophylaxis among CMV-seropositive SOT recipients. Likewise, CMV-specific cell-mediated immunity assays have been suggested to inform the need for secondary antiviral prophylaxis and immunologic optimization to prevent CMV relapse after treatment. Conclusions: CMV-specific cell-mediated immune assays are emerging to assist transplant clinicians in predicting a patient’s risk of CMV after transplantation, and these assays have been utilized to individualize the approach to CMV prevention and treatment. The author suggests the conduct of more interventional studies to further solidify the role of CMV-specific cell-mediated immune assays in routine clinical practice.

ABSTRACTBackgroundPreventive strategies for cytomegalovirus (CMV) in the posttransplant period have changed the pattern of CMV infections, now more commonly manifesting as late‐onset occurrences known as post‐prophylaxis delayed‐onset CMV disease (PPDOC). We conducted a survey to investigate provider practices in managing PPDOC.MethodsA web‐based provider survey on the management of PPDOC was developed using Research Electronic Data Capture (REDCap). It was distributed to the online forums of the American Society of Transplantation communities of practice (COP) for Infectious Diseases (IDCOP), Kidney and Pancreas (KPCOP), Liver and Intestinal (LICOP), and Thoracic and Critical Care (TCCOP). The survey was posted twice within a span of a month.ResultsFifty‐six respondents, comprising 50 (89%) transplant physicians and 6 (11%) transplant pharmacists, from 46 distinct transplant centers, completed the survey. Universal antiviral prophylaxis (UAP) was the predominant preventive approach for both high‐risk (85%) and moderate‐risk (85%) transplant recipients. Out of 56, 51 respondents completed the questions regarding management of PPDOC. Regular surveillance with nucleic acid amplification tests (NAAT) (88%) was the most commonly used approach in high‐risk recipients, while symptom monitoring (73%) was the most common strategy in moderate‐risk recipients. Immunologic monitoring was used only by a few respondents who found it moderately useful in high‐risk recipients.ConclusionManagement of PPDOC was highly variable among providers and strategies differed based on patient risk profile. These findings could help shape future studies and guidelines to harmonize CMV management.