ABSTRACT
In this report, the authors present a detailed immunological and virological assessment of an immunocompetent 17-year-old Caucasian male with a fatal Epstein-Barr virus (EBV) infectious mononucleosis presenting with meningoencephalitis and hemophagocytic syndrome. The patient with serologically confirmed EBV infectious mononucleosis was admitted to the hospital because of 3 weeks' fever. Fine-needle aspiration of lymph nodes showed reactive hyperplasia with prominent hemophagocytosis. Percentages of intracellular interferon-gamma (IFN-gamma) in CD4(+) and CD8(+) T cells in the peripheral blood progressively increased during the course of disease (10.2% and 8.5% on day 35; 30.1% and 53.2% on day 44; 42.2% and 75.2% on day 50; 36.1% and 50.6% on day 59, respectively). On day 50, the patient developed meningoencephalitis. Brain computed tomography (CT) was normal. Brain magnetic resonance imaging (MRI) showed multifocal inflammatory lesions in frontal and temporal cortex of the right hemisphere as well as severe perivascular inflammatory reaction. The patient was treated with steroids, cyclosporin A, and methotrexate intratecally. Following treatment, EBV viremia in the blood and cerebrospinal fluid (CSF) decreased from pretreatment values (54,490 copies of EBV DNA/ml and 39,500 copies/ml, respectively) to 8715 copies/ml in the blood and 14,690 in the CSF. Despite treatment, the patient remained unconscious and died of sepsis and pneumonia 3 months after initial symptoms. Immunohistochemical staining showed the presence of EBV in both perivascular infiltrates and grey matter. Enhanced Th1 response as shown by high levels of IFN-gamma in peripheral blood lymphocytes may be a predictor of severe complications during acute EBV infection. Early implementation of immunosuppressive therapy in these patients should be considered.
Subject(s)
Herpesvirus 4, Human/immunology , Infectious Mononucleosis/immunology , Lymphohistiocytosis, Hemophagocytic/immunology , Lymphohistiocytosis, Hemophagocytic/virology , Meningoencephalitis/immunology , Meningoencephalitis/virology , Adolescent , Biopsy , Brain/pathology , Brain/virology , Humans , Infectious Mononucleosis/pathology , Interferon-gamma/metabolism , Lymphocyte Subsets/immunology , Lymphocyte Subsets/metabolism , Lymphohistiocytosis, Hemophagocytic/pathology , Male , Meningoencephalitis/pathologyABSTRACT
The aim of this study was to evaluate the performance of a molecular assay for quantitation of Epstein-Barr virus (EBV) DNA based on real-time PCR, and to determine EBV DNA levels in EDTA whole blood samples derived from different groups of patients. Following a manual DNA extraction protocol, real-time PCR was performed using the LightCycler EBV Quantification Kit, which demonstrated sufficient accuracy and linearity. Coefficients of variations were found to be between 6 and 42% and 5 and 34%, respectively, for inter-assay and intra-assay variations. In clinical specimens, EBV DNA was detected in all patients with acute EBV infection (n=34), in one of 25 adults with past EBV infection, in 16 out of 25 (64%) anti-HIV antibody positive persons, in 10 out of 25 (40%) solid organ transplant recipients, and in none of the 23 infants without history of EBV infection. When EBV DNA levels in positive specimens were compared between different groups, statistically significant differences were not found. The LightCycler EBV Quantification Kit was found to be useful for determination of EBV DNA levels in EDTA whole blood.
