A new study suggests that HHV-6 and HHV-7 are important co-factors for the development of CMV infection post-transplant in allogeneic hematopoietic stem cell transplantation patients. Additionally, the presence of HHV-7 and CMV together may result in more severe infections than either virus alone.
In a French study of 366 adult allogenic hematopeietic stem cell transplantation (aHSCT) recipients CD8+ T cell recovery was significantly reduced in patients with HHV-6 reactivation. HHV-6 reactivation was also associated with reduced survival and increased infections of CMV and BKV.
Researchers from Stanford University successfully used circulating cell-free DNA to identify infections in lung transplants that can often be found only with a more invasive transbronchial biopsy. This hypothesis free approach led to find HHV-6 & 7 at high levels in patients with infections, even though these viruses are not generally considered lung pathogens.
A hematology group in Australia reported a case of biopsy-proven HHV-6 myocarditis post-hematopoietic stem cell transplantation (HSCT). he post-mortem exam confirmed dilated cardiomyopathy and focal changes consistent with viral myocarditis and cardiac tissue was positive for HHV-6 DNA by nested and quantitative PCR. Separately, A Japanese group reported a worman who developed pericarditis with over 10,000 copies/ml of HHV-6 DNA in the pericardial fluid, after a cord blood transplant.
A group of researchers from Sao Paulo, Brazil reported the development of HHV-6 infection in the striatum of a 32-year-old man six weeks after allogeneic hematopoietic stem cell transplantation. This is the first reported case of HHV-6 infection affecting the striatum and presenting with Parkinsonism post-HSCT.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four patients (3.8%) were diagnosed with HHV-6 encephalitis. The group used a qualitative multiplex PCR and then used a quantitative PCR to confirm the results.
A prospective study authored by Joshua Hill and Danielle Zerr determined that higher than average HHV-6B DNA levels increased the odds of developing delirium after cord blood transplantation (CBT) by almost three fold. Patients with DNA loads in the top quartile had a 4.5 fold increase in delirium.
HHV-6 may be the cause of “fever of unknown origin” in 30% of stem cell transplant (SCT) patients. By the third week after SCT, 70% of HHV-6 positive patients had a skin rash, compared to 39% of HHV-6 negative patients.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four or 3.8% of the population were diagnosed with HHV-6 encephalitis.
In an article published in the Pediatric Infectious Disease Journal, Tetsushi Yoshikawa’s team from Fujita Health University School of Medicine determined that the severe neutropenia in primary HHV-6B infection is tied to reduced platelet counts, lower RANTES and higher levels of MCP-1, MIG and IP-10.
A large-scale multiplex PCR assay developed by a team in Japan was used to study 13 DNA viruses in 105 allogenic hematopoietic stem cell transplant patients. They found that patients treated with steroids had a significantly higher risk of HHV-6 reactivation (p=0.027), and that HHV-6 was the only virus tied to the onset of acute GVHD (p=0.016).
Intensive care (ICU) patients with co-infections of HHV-6 and CMV are 7.5x more likely to die or have an extended stay in the hospital. On the other hand, single infections with either HHV-6 or CMV did not significantly impact outcome.
A large-scale multiplex PCR assay developed by a team in Japan was used to study 13 DNA viruses in 105 allogenic hematopoietic stem cell transplant patients. Their findings identify HHV-6 as the most common virus (found in 60% of all patients), and also as the only virus tied to the onset of acute GVHD (p=0.016). Interestingly, HHV-6 reactivation was associated with a more severe stage of skin but not liver or gut aGVHD (P=0.005). In addition, patients treated with steroids had a significantly higher risk of HHV-6 reactivation (p=0.027) and cord blood transplant patients were 10.4x more likely to reactivate with HHV-6. The authors looked at the association of HHV-6 reactivation in the absence of GVHD, and found that it …
Dr. Flamand, a professor and molecular virologist at Université Laval in Quebec city, has written an editorial calling for screening of organ donors for ciHHV-6 status and careful monitoring of recipients of ciHHV-6 donor tissues for signs of active HHV-6 infection and HHV-6 antigen-induced immune rejection. Flamand also questions whether solid organs and stem cells derived from persons with ciHHV-6 should be used in transplantation.
Should physicians automatically discount HHV-6 if any other pathogen is found in the CSF? Should patients with both HHV-6 and EBV DNA in the CSF be treated only for EBV? These are the questions that UW group tried to sort out in this study.