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TNF-α predicts HHV-6 reactivation and disease progression in patients with DIHS/DRESS

HHV-6 has long been associated with drug hypersensitivity reaction syndromes such as DIHS/DRESS.  However, the specific mechanism of this relationship has yet to be fully elucidated, and to date there have been no widely accepted biomarkers of the DIHS/DRESS disease process.  In a recent study from Japan, a serum TNF-a level of 12 pg/mL, CRP level of 7 mg/dl, and LDH level of 600 U/L were found to be sufficient for prediction of HHV-6 reactivation in this patient population. The TNF-a threshold was particularly correlated with HHV-6 DNA detection, and additional data suggest IL-6 and TNF-a may be good indicators of DIHS/DRESS disease progression overall.  While elevated TNF-a detected at the early onset of disease is a strong indicator for the early recognition of HHV-6 reactivation, this finding also reflects important therapeutic information that could be used as an early diagnostic marker of DIHS/DRESS.  In addition, IL-6 was found to be a good marker to differentiate DIHS from erythema multiforme. READ MORE

New strategy for reducing rate of encephalitis in cord blood transplant patients?

Previous studies have revealed that 8-10% of cord blood transplant recipients go on to develop HHV-6 encephalitis, often with serious sequelae.  HHV-6 reactivation in transplant patients can cause hepatitis, intersitital pneumonia, fever, rash, cognitive dysfunction and delayed neutrophil and platelet engraftment. Investigators at Sloan Kettering’s adult transplant center may have found a formula to keep this rate of encephalitis low. In an article published this month, the group shows data from a cohort of 125 double-unit CBT recipients that eliminating anti-thymocyte globulin (ATG) from the regimen may help limit the rate of HHV-6 encephalitis in these patients.  In addition, the group administered antivirals (foscarnet) to symptomatic HHV-6+ patients. While nearly every patient enrolled in the study experienced HHV-6 reactivation (94%), HHV-6 encephalitis occurred in just 2 patients (1.6%).  READ MORE

Mixed and compartmentalized infections found in Japanese stem cell transplant patients

Mixed CMV infections have been linked to high viral loads and worse prognosis in transplant patients. A team of Japanese investigators led by Tetsushi Yoshikawa found evidence of mixed infections of human herpesvirus 6B (HHV-6B) in two out of 15 stem cell transplant patients. Furthermore, in two patients the strain in the spinal fluid differed from that in the peripheral blood, suggesting compartmentalization of HHV-6 reactivation.  The analysis was done by quantifying the copy numbers of telomeric repeat sequences (TRS) among various clinical isolates in immunocompetent and immunocompromised individuals. These repeat sequencs are located at the ends of the HHV-6 genome and vary considerably by strain.  The investigators then compared telomeric sequences In clinical isolates obtained from exanthem subitum cases to those from patients with DIHS or post-transplant reactivation. The sizes of the telomeric sequences in each strain differ considerably, making it possible to determine the number of variants without isolating each strain individually.  In this case, the reactivated virus detected in the CNS differed from that of the virus detected in initial isolates from PBMCs. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for determining the number of isolates present in a sample, which in turn may have important clinical relevance in several clinical contexts of HHV-6B infection.  READ MORE

Understanding the association between ciHHV-6 and HIV disease

A group from the University of Rochester Medical Center led by Mary Caserta has conducted a cross-sectional investigation to identify evidence of a potential modifying effect of chromosomally integrated human herpes virus 6 (ciHHV-6) on human immunodeficiency virus (HIV) disease progression and/or severity. They found 8 ciHHV6 patients out of 439 with HIV, or a prevalence of 0.91%.  After adjusting for use of antiretroviral therapy, all subjects with ciHHV-6 were found to have experienced low severity HIV disease. Although these results were not statistically significant, the authors suggest a larger study of HIV disease severity and ciHHV6 status is needed to fully understand this relationship. READ MORE