Japanese investigators evaluated cytokines and chemokines in the CSF and plasma in HHV-6 encephalitis patients with good and poor prognoses. They found IL-6, IL-7, MCP-1 to be elevated one week before onset, suggesting that these cytokines may be effective targets for intervention.
Researchers from GlaxoSmithKline found a significant overlap in differentially expressed genes shared by those with herpesvirus infections, Alzheimer’s and Parkinson’s. On the other hand, there was no significant overlap between herpesviruses and Type 2 diabetes or Huntington’s disease.
A Mayo clinic review of long-term outcome of patients with HHV-6 encephalitis showed that over 60% showed persistent sequelae associated with severe bilateral hippocampal atrophy. Symptoms included anterograde amnesia, aphasia, headaches, confusion and persistent memory deficits.
A rapid point-of-care test for patients with encephalitis and meningitis was heralded as a breakthrough, but because the test is not able to determine ciHHV-6 status or viral load, it now has physicians frustrated over how to interpret a positive result.
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 …
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.