An abstract at the Transplantation & Cellular Therapy Meeting in Houston showed that only 2% of 92 patients treated with oral brincidofovir developed high level reactivation compared to 11% of 61 patients taking the placebo. The results came from an analysis of stored samples from their previous Phase III SUPPRESS trial for CMV prophylaxis. Chimerix’s Phase III trial for cytomegalovirus failed. Although oral brincidofovir reduced CMV viremia during the first 14 weeks, CMV infections bounced back during the 10-week observation period that followed, and there was a higher mortality rate in the drug group. Analysts blamed the higher death rate on the inability of participating physicians to differentiate between bleeding (a side effect of the drug) and acute GVHD. Instead …
89% of the virus found in the spinal fluid of HCT patients in the first 60 days is HHV-6
An analysis of 165 central nervous system viral infections by the Center for International Blood and Bone Marrow Transplant Research found that most were positive for HHV-6. The outcome for patients with viral infection was poor with 50% mortality within 6 months and only 30% survival at 5 years.
Mycophenolate mofetil tied to increased risk of HHV-6 encephalitis after allogenic transplantation
Japanese investigators found that those who were administered mycophenolate mofetil along with a calcineurin inhibitor developed a much higher rate of infection: 12% in cord blood and 6% in other transplants.
HHV-6 and EBV found in the brain tissue of Rasmussen’s Encephalitis patients
Chinese investigators found a high prevalence of HHV-6 and Epstein Barr virus in the brain tissues of children with Rasmussen’s encephalitis but in none of the controls. There was a significant association between viral presence and brain atrophy, raising a strong suspicion for the involvement of both viruses.
Acute seizures in children: a new study highlights the role of infections and inflammation
NINDS investigators found that children with febrile seizures have elevated inflammatory cytokines compared to healthy controls and children with fever. One of those cytokines, Il-1β, correlated with HHV-6 saliva viral load.
Why did these transplant protocols result in such a high rate of HHV-6 encephalitis (32%) and organ disease (46%)?
Investigators in Spain and Italy attempted to reduce the rate of acute GVHD in pediatric transplant patients by infusing manipulated stem cells. Not only was there no reduction in expected acute GVHD, the patients experienced an unusually high rate of HHV-6 disease.
HHV-6 encephalitis in 32% of pediatric leukemia patients depleted of naïve T cells
Although depleting naïve T cells has been successful in preventing acute graft vs host disease in several studies, investigators from Spain reported an unexpectedly high incidence of HHV-6 encephalitis in a cohort of haploidentical transplant patients.
FilmArray encephalitis/meningitis panel causing confusion due to undiagnosed ciHHV-6
Many institutions are now using a new multiplex qualitative assay to get rapid diagnosis in encephalitis cases in the clinic. Unfortunately, this system cannot identify cases of inherited chromosomal integration, which creates confusion.
Foscarnet prophylaxis reduces severity but does not prevent HHV-6 encephalitis
A Japanese trial of foscarnet prophylaxis in cord blood transplant patients was successful in reducing severity and mortality as well as suppressing high viral loads, but it failed to prevent encephalitis. The authors note that the blood brain barrier must be inflamed to allow effective penetration of the drug into the central nervous system and speculate that the prophylaxis may have protected the meninges.
Dense infection of the hippocampus in primary HHV-6B encephalitis
The autopsy of an infant with HHV-6B encephalitis showed a 4-5 fold increase in the viral load of the hippocampus compared to other parts of the brain. Neurons, oligodendrocytes and vascular endothelial cells were infected, but not astrocytes or microglia.
New study details devastating impact of HHV-6 encephalitis
Investigators in Japan studied 145 patients who developed HHV-6 encephalitis. At 100 days after transplantation, the overall survival rate was just 58.3%, compared with 80.5% for patients who did not develop encephalitis. High-dose antiviral therapy was shown to mitigate high mortality rates in these patients.
HHV-6 induced amnesia after rituximab therapy for autoimmune disease
A young woman on rituximab and two other immunomodulatory agents for the treatment of dermatomyositis developed encephalitis with severe anterograde amnesia. As the use of biologic treatments for refractory autoimmune disease has been increasing, physicians are advised to consider HHV-6 and offer prompt antiviral therapy to limit irreversible morbidity.
HHV-6 encephalopathy associated with structural changes in the olfactory pathway
Latvian researchers studied autopsy material from the olfactory bulb in patients with HHV-6 encephalopathy vs. controls and reported surprising differences.
Rapid point-of-care system screens for 14 encephalitis pathogens in one hour!
A new point-of-care assay from bioMérieux can simultaneously and rapidly detect 14 pathogens typically found in encephalitis. The machine is designed to be at the clinic or in the emergency room and can be operated by unskilled technicians. In a study of 1,560 immunocompetent patient samples, a total of 1.35% were positive for HHV-6, or about twice the expected rate of 0.8% found with the inherited chromosomally integrated HHV-6.
GAD antibodies & HHV-6 limbic encephalitis – a case of molecular mimicry?
A fifth case of limbic encephalitis associated with GAD antibodies and HHV-6 infection has been reported, this time in an immunocompetent woman with chromosomally integrated HHV-6, epilepsy, and psychosis. The patient’s condition improved (with a drop in GAD antibody titers and stabilization of psychotic symptoms) in response to three weeks of antiviral therapy but relapsed when antiviral therapy was withdrawn.
