Clinical characteristic and outcome of HHV-6 encephalitis after allogeneic hematopoietic cell transplantation: A study of Infectious Disease Working Party of EBMT.

Human herpes virus-6 (HHV-6) is the main cause of viral encephalitis in patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT). From January 2005 to December 2014, 97 patients with HHV-6 encephalitis were reported in the EBMT registry. The incidence was 0.

An interactive data visualisation application to investigate nosocomial transmission of infections.

Healthcare-associated infections represent a major threat to patient, staff and visitor safety. Identification of episodes that are likely to have resulted from nosocomial transmission has important implications for infection control. Routinely collected data on ward admissions and sample dates, combined with pathogen genomic information could provide useful insights.

Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7).

Cytomegalovirus is one of the most important infections to occur after allogeneic haematopoietic stem cell transplantation (HSCT), and an increasing number of reports indicate that cytomegalovirus is also a potentially important pathogen in patients treated with recently introduced drugs for hematological malignancies. Expert recommendations have been produced by the 2017 European Conference on Infections in Leukaemia (ECIL 7) after a review of the literature on the diagnosis and management of cytomegalovirus in patients after HSCT and in patients receiving other types of therapy for haematological malignancies. These recommendations cover diagnosis, preventive strategies such as prophylaxis and pre-emptive therapy, and management of cytomegalovirus disease.

A survey on incidence and management of adenovirus infection after allogeneic HSCT.

To determine the current practices on the management of Adenovirus (ADV) infection after allogenic stem cell transplantation, a survey was undertook among EBMT centres. The response rate was 20% (91/446): 46% were adult, 44% were paediatric and 10% were mixed centres, respectively. The overall incidence of ADV infection was 7.

Impact of Donor Epstein-Barr Virus Serostatus on the Incidence of Graft-Versus-Host Disease in Patients With Acute Leukemia After Hematopoietic Stem-Cell Transplantation: A Study From the Acute Leukemia and Infectious Diseases Working Parties of the European Society for Blood and Marrow Transplantation.

Purpose: We investigated the effect of Epstein-Barr virus (EBV) serostatus on the overall outcome of allogeneic hematopoietic stem-cell transplantation (allo-HSCT).

Patients And Methods: The study included 11,364 patients who underwent allogeneic peripheral-blood or bone marrow transplantation for acute leukemia between 1997 and 2012. We analyzed the impact of donor and recipient EBV serologic status on overall survival, relapse-free survival, relapse incidence, nonrelapse mortality, and incidence of graft-versus-host disease (GVHD) after allo-HSCT.

Donor cytomegalovirus status influences the outcome of allogeneic stem cell transplant: a study by the European group for blood and marrow transplantation.

Background: The use of a cytomegalovirus (CMV)-seronegative donor for a CMV-seronegative allogeneic hematopoietic stem cell transplant (HSCT) recipient is generally accepted. However, the importance of donor serostatus in CMV-seropositive patients is controversial.

Methods: A total of 49 542 HSCT patients, 29 349 seropositive and 20 193 seronegative, were identified from the European Group for Blood and Marrow Transplantation database.

Delayed primary HHV-7 infection and neurologic disease.

Background: Primary human herpesvirus 7 (HHV-7) infection occurs almost universally during the first 5 years of life and is rarely accompanied by central nervous system (CNS) symptoms such as febrile seizures. The present retrospective study investigated the role of primary HHV-7 infection in CNS disease in children, including adolescents.

Methods: The study included all children who had neurologic disease aged younger than 18 years seen at the Hospital for Sick Children, Toronto, Canada, between April 1, 1998 and December 31, 2011, whose cerebrospinal fluid (CSF) was found by polymerase chain reaction to contain HHV-7 DNA.

Child and adult forms of human herpesvirus 6 encephalitis: looking back, looking forward.

Purpose Of Review: This review evaluates publications on human herpesvirus 6 (HHV-6) encephalitis recognizing firstly that HHV-6A and HHV-6B are separate species with differing properties, and secondly the phenomenon of chromosomal integration; this occurs in a minority of persons and the complete viral genome of either HHV-6A or HHV-6B is present in every nucleated cell in the body. Although chromosomal integration has not been associated with disease, the resulting very high level of viral DNA in human tissues and blood has sometimes been wrongly misinterpreted as active infection.

Recent Findings: No disease has been linked to HHV-6A, whereas HHV-6B may cause encephalitis.

Fourth European Conference on Infections in Leukaemia (ECIL-4): guidelines for diagnosis and treatment of human respiratory syncytial virus, parainfluenza virus, metapneumovirus, rhinovirus, and coronavirus.

Community-acquired respiratory virus (CARV) infections have been recognized as a significant cause of morbidity and mortality in patients with leukemia and those undergoing hematopoietic stem cell transplantation (HSCT). Progression to lower respiratory tract infection with clinical and radiological signs of pneumonia and respiratory failure appears to depend on the intrinsic virulence of the specific CARV as well as factors specific to the patient, the underlying disease, and its treatment. To better define the current state of knowledge of CARVs in leukemia and HSCT patients, and to improve CARV diagnosis and management, a working group of the Fourth European Conference on Infections in Leukaemia (ECIL-4) 2011 reviewed the literature on CARVs, graded the available quality of evidence, and made recommendations according to the Infectious Diseases Society of America grading system.

Adenoviremia has limited clinical impact in the majority of patients following alemtuzumab-based allogeneic stem cell transplantation in adults.

Background: Adenovirus infection is a potentially serious complication of allogeneic hematopoietic stem cell transplantation (HSCT) and has been reported to occur more frequently following T-cell-depleted reduced-intensity HSCT. However, the true incidence and clinical significance as well as the relationship of disease to viremic titer remain unclear due to wide variation in study populations and methodology.

Methods: We performed weekly surveillance blood testing by quantitative polymerase chain reaction on all adult recipients of alemtuzumab-based reduced-intensity HSCT at our institution between January 2008 and January 2011.

Chromosomally integrated human herpesvirus 6: questions and answers.

Chromosomally integrated human herpesvirus 6 (ciHHV-6) is a condition in which the complete HHV-6 genome is integrated into the host germ line genome and is vertically transmitted in a Mendelian manner. The condition is found in less than 1% of controls in the USA and UK, but has been found at a somewhat higher prevalence in transplant recipients and other patient populations in several small studies. HHV-6 levels in whole blood that exceed 5.

Herpes simplex serious neurological disease in young children: incidence and long-term outcome.

Objective: To determine the contribution of herpes simplex virus (HSV) to serious neurological disease.

Setting And Patients: A 3-year prospective survey of children aged 2-23 months in Britain and Ireland.

Results: 19 children had HSV central nervous system (CNS) infection; 13 aged 2-11 months had focal neuroimaging abnormalities and 11 long-term neurological sequelae.

Outcome of pandemic H1N1 infections in hematopoietic stem cell transplant recipients.

During 2009, a new strain of A/H1N1 influenza appeared and became pandemic. A prospective study was performed to collect data regarding risk factors and outcome of A/H1N1 in hematopoietic stem cell transplant recipients. Only verified pandemic A/H1N1 influenza strains were included: 286 patients were reported, 222 allogeneic and 64 autologous recipients.

Causes of encephalitis and differences in their clinical presentations in England: a multicentre, population-based prospective study.

Background: Encephalitis has many causes, but for most patients the cause is unknown. We aimed to establish the cause and identify the clinical differences between causes in patients with encephalitis in England.

Methods: Patients of all ages and with symptoms suggestive of encephalitis were actively recruited for 2 years (staged start between October, 2005, and November, 2006) from 24 hospitals by clinical staff.

Importance of chromosomally integrated HHV-6A and -6B in the diagnosis of active HHV-6 infection.

Human herpesvirus-6 (HHV-6) exists as two closely related variants: A and B. Whereas no disease has been firmly associated with HHV-6A, variant B causes febrile illness in young children and is pathogenic in immunosuppressed transplant recipients. Chromosomally integrated HHV-6 (with either variant A or B) occurs in a minority of people.

HHV-6 DNA throughout the tissues of two stem cell transplant patients with chromosomally integrated HHV-6 and fatal CMV pneumonitis.

Two patients with the characteristic high human herpesvirus 6 (HHV-6) DNA loads in peripheral blood caused by chromosomally integrated (CI) virus received a haematopoietic stem cell transplant (HSCT) from a donor without CI HHV-6. Both patients died in consequence of cytomegalovirus (CMV) pneumonitis. At autopsy, high amounts of CMV DNA were detected in lungs but at much lower levels in other organs.

Human herpesvirus 6 integrates within telomeric regions as evidenced by five different chromosomal sites.

Fluorescent in situ hybridization (FISH) was used to investigate the chromosomal integration sites of human herpesvirus 6 (HHV-6) in phytohemagglutinin-stimulated leukocytes and B lymphocytes from Epstein-Barr virus transformed lymphoblastoid cell lines (LCLs). Five different chromosomal integration sites were found in nine individuals. Only one site was identified in each individual, each site was in the vicinity of the telomeric region and was on either the p or q arm of only one of the two chromosome homologues.

Risk of serious neurologic disease after immunization of young children in Britain and Ireland.

Objective: We sought to investigate the risk of serious neurologic disease after immunization in early childhood.

Methods: The results of a 3-year prospective study of children (2-35 months old) in Britain and Ireland with encephalitis and/or severe illness with convulsions and fever were linked to each child's vaccine history. Cases were reported via the British Paediatric Surveillance Unit's network.

Molecular investigations of an outbreak of parainfluenza virus type 3 and respiratory syncytial virus infections in a hematology unit.

A large simultaneous outbreak of respiratory syncytial virus (RSV) and parainfluenza type 3 (PIV-3) infections occurred on an adult hematology unit. Implementation of enhanced infection control was complicated by cocirculation of the two different viruses, with prolonged viral shedding from infected patients, and placed great pressure on health care staff; of 27 infected hematopoietic stem cell transplant patients, 9 died, and the unit was closed for 2 months. Retrospective molecular investigation of the virus strains involved in the outbreak was performed by analyzing part of the fusion gene of PIV-3 and part of the glycoprotein gene of RSV.

Human herpesvirus 6 DNA levels in cerebrospinal fluid due to primary infection differ from those due to chromosomal viral integration and have implications for diagnosis of encephalitis.

The prevalence and concentration of human herpesvirus 6 (HHV-6) DNA in the cerebrospinal fluid (CSF) of the immunocompetent in primary infection was compared with that in viral chromosomal integration. Samples from 510 individuals with suspected encephalitis, 200 young children and 310 older children and/or adults, and 12 other patients were tested. HHV-6 DNA concentration (log(10) copies/ml) was measured in CSF, serum, and whole blood using PCR.

The prevalence of chromosomally integrated human herpesvirus 6 genomes in the blood of UK blood donors.

A lesser-recognized form of human herpesvirus 6 (HHV-6) persistence is integration of the viral genome in a host chromosome and high viral copy numbers in blood or sera are characteristic of this phenomenon. A cross-sectional study was performed to determine the frequency of high HHV-6 viral loads in whole blood (>6 log(10) copies/ml) in a population of blood donors in London, UK. Blood samples from 500 anonymized blood donors were collected from one donation center, DNA extracted, and quantitative realtime PCR used to measure viral load.

Human herpesvirus 6 chromosomal integration in immunocompetent patients results in high levels of viral DNA in blood, sera, and hair follicles.

Six immunocompetent patients with human herpesvirus 6 (HHV-6) chromosomal integration had HHV-6 and beta-globin DNA quantified in various samples by PCR. The mean HHV-6 DNA concentration (log(10) copies/milliliter) in blood was 7.0 (>/=1 HHV-6 DNA copies/leukocyte), and in serum it was 5.

Unexpected occasional persistence of high levels of HHV-6 DNA in sera: detection of variants A and B.

Previously it was thought that in the immunocompetent human herpesvirus-6 [HHV-6] DNA was present transiently in serum during early primary infection but not thereafter. In this study, HHV-6 serum IgG avidity was detected by immunofluorescence and HHV-6 variants A/B [HHV-6A/B] serum DNA by semi-quantitative PCR [titre-log(10) copies/ml] in: (a) young children <3 years old from an encephalitis Survey, and a control Anonymised Serum Bank and (b) children/adults referred for diagnosis. The results showed that 11 out of 15 children [all <2 years] with primary infection proven by seroconversion had transient low levels of serum HHV-6B DNA [mean titre 2.