Roseola Research Articles

HHV-6 is an emerging neuro- and lymphotropic virus with multiple disease associations

Human herpesvirus 6 (HHV-6) is a highly neuro- and lymphotropic virus with an increasing number of diseases associated with it. Most children are infected at the age of 6 to 15 months. Primary infection manifests classically as exanthema subitum. This is, however, only one aspect of the clinical spectrum of the disease. Neurological symptoms are common and the virus may persist in several tissues and cells and be reactivated in various immunosuppressive conditions. In addition, HHV-6 may be involved in many chronic diseases. The two variants HHV-6A and HHV-6B appear to have different disease associations. To conclude, diseases associated with or caused by HHV-6 seem to expand. HHV-6 needs attention and active research both in children and in adults.

Predicting the characteristics of the aetiological agent for Kawasaki disease from other paediatric infectious diseases in Japan.

Although Kawasaki disease (KD), which was first reported in the 1960s, is assumed to be infectious, its aetiological agent(s) remains unknown. We compared the geographical distribution of the force of infection and the super-annual periodicity of KD and seven other paediatric infectious diseases in Japan. The geographical distribution of the force of infection, which was estimated as the inverse of the mean patient age, was similar in KD and other paediatric viral infections. This similarity was due to the fact that the force of infection was determined largely by the total fertility rate. This finding suggests that KD shares a transmission route, i.e. sibling-to-sibling infection, with other paediatric infections. The super-annual periodicity, which is positively associated with the sum of an infectious disease's incubation period and infectious period, was much longer for KD and exanthema subitum than other paediatric infectious diseases. The virus for exanthema subitum is known to persist across the host's lifespan, which suggests that the aetiological agent for KD may also be capable of persistent infection. Taken together, these findings suggest that the aetiological agent for KD is transmitted through close contact and persists asymptomatically in most hosts.

ÇOCUKLARDA ATEŞLİ DÖKÜNTÜLÜ HASTALIKLAR

Fever accompanied by rash is a common complaint in pediatric practice. Mostly these conditions are caused by different viruses and self-limited. But, it may also be the first and only sign of serious and life-threatening bacterial infections, like meningococcemia and bacterial sepsis. The most important step in the diagnostic process is a detailed clinical examination. A detailed physical examination can easily lead the physician to the correct diagnosis. The rash in children is often maculopapular and nonspecific. However a petechial rash should be evaluated as meningococcemia until the contrary is proven. Most common diseases presenting with fever and rash are measles, rubella, scarlet fever, erythema infectiosum, roseola infantum, Epstein-Barr virus infection, cytomegalovirus (CMV) infections, Kawasaki disease and for our country Crimean-Congo hemorrhagic fever

Pathogenic Role of Human Herpesvirus 6B Infection in Mesial Temporal Lobe Epilepsy.

Human herpesvirus 6B (HHV-6B) is the causative agent for exanthem subitum. HHV-6B was associated with mesial temporal sclerosis (MTS), leading to mesial temporal lobe epilepsy (MTLE). In this study, we sought to elucidate the pathogenic role of HHV-6B in patients with MTLE. Seventy-five intractable MTLE patients, including 52 MTS patients and 23 non-MTS patients, were enrolled in this study. Resected hippocampus, amygdala, and mixed samples of amygdala and uncus samples were examined by real-time polymerase chain reaction (PCR) and reverse-transcriptase PCR to detect viral DNA and messenger RNA (mRNA), respectively. Host gene expressions, including neural markers, were measured using the TaqMan Gene Expression Assay. Detection of HHV-6 DNA was higher in MTS patients than non-MTS patients (median/interquartile range: 19.1/0-89.2 vs 0.0/0.0-0.0 copies/µg DNA; P = .004). HHV-6B viral DNA was determined in 12/27 HHV-6 DNA-positive samples, and no HHV-6B mRNA were detected in all samples. In MTS patients, expression of monocyte chemotactic protein-1 (P = .029) and glial fibrillary acidic protein (P = .043) were significantly higher in the amygdala samples with HHV-6 DNA than those without viral DNA. This study suggests that HHV-6B may play an important role in the pathogenesis of MTS via modification of host gene expression.

Laboratory and clinical aspects of human herpesvirus 6 infections.

Human herpesvirus 6 (HHV-6) is a widespread betaherpesvirus which is genetically related to human cytomegalovirus (HCMV) and now encompasses two different species: HHV-6A and HHV-6B. HHV-6 exhibits a wide cell tropism in vivo and, like other herpesviruses, induces a lifelong latent infection in humans. As a noticeable difference with respect to other human herpesviruses, genomic HHV-6 DNA is covalently integrated into the subtelomeric region of cell chromosomes (ciHHV-6) in about 1% of the general population. Although it is infrequent, this may be a confounding factor for the diagnosis of active viral infection. The diagnosis of HHV-6 infection is performed by both serologic and direct methods. The most prominent technique is the quantification of viral DNA in blood, other body fluids, and organs by means of real-time PCR. Many active HHV-6 infections, corresponding to primary infections, reactivations, or exogenous reinfections, are asymptomatic. However, the virus may be the cause of serious diseases, particularly in immunocompromised individuals. As emblematic examples of HHV-6 pathogenicity, exanthema subitum, a benign disease of infancy, is associated with primary infection, whereas further virus reactivations can induce severe encephalitis cases, particularly in hematopoietic stem cell transplant recipients. Generally speaking, the formal demonstration of the causative role of HHV-6 in many acute and chronic human diseases is difficult due to the ubiquitous nature of the virus, chronicity of infection, existence of two distinct species, and limitations of current investigational tools. The antiviral compounds ganciclovir, foscarnet, and cidofovir are effective against active HHV-6 infections, but the indications for treatment, as well as the conditions of drug administration, are not formally approved to date. There are still numerous pending questions about HHV-6 which should stimulate future research works on the pathophysiology, diagnosis, and therapy of this remarkable human virus.

Analysis of ganciclovir-resistant human herpesvirus 6B clinical isolates using quenching probe PCR methodology.

Quenching probe PCR (QP-PCR) analysis was used to determine the frequency of ganciclovir (GCV) resistance among clinical isolates of human herpesvirus 6B (HHV-6B) obtained from patients with primary viral infection and viral reactivation. Forty-two HHV-6B clinical isolates were repeatedly recovered from 15 hematopoietic stem cell transplant (HSCT) recipients, and 20 isolates were recovered from 20 exanthem subitum (ES) patients. Of the 15 HSCT recipients, 9 received GCV during the observation period; however, none of the ES patients were treated with GCV. Two established laboratory strains, Z29 and HST, were used as standards in this study. Regions 1 and 2 of the U69 gene of all of the clinical isolates demonstrated the same melting temperature as regions 1 and 2 of the Z29 strain. For region 3, the melting temperatures of all clinical isolates fell between the melting temperature of the plasmid containing the A462D single nucleotide polymorphism (SNP) and the melting temperature of the Z29 strain, and the melting temperatures profiles of all clinical isolates were similar to the melting temperature profile of the Japanese HST strain. As expected, none of the 20 clinical isolates recovered from the ES patients and the 14 isolates recovered from the HSCT recipients who did not receive GCV treatment carried the six known SNPs associated with GCV resistance. Interestingly, these six SNPs were not detected in the 28 clinical isolates recovered from the 9 HSCT recipients who received GCV. Additional sequence analysis of the U69 gene from the 15 representative isolates from the 15 HSCT recipients identified other SNPs. These SNPs were identical to those identified in the HST strain. Therefore, the rate of emergence of GCV-resistant HHV-6B strains appears to be relatively low, even in HSCT recipients treated with GCV.

Prevalence of Human Herpes Virus 6 (HHV-6) in Patients with Hemodialysis

HHV-6 is the causative agent of exanthema subitum in children. The main modes of transmission of HHV-6 arebody secretions such as infected saliva but it can be transmitted with blood and blood products that are infected with\the virus. Therefore, it is thought that the immunocompromised hemodialysis patients who had multiple bloodtransfusions due to various reasons, and who collectively use devices such as hemodialysis machines are at risk forHHV-6 infection. The present study aimed to determine the incidence of HHV-6 infection in hemodialysis patients. Twenty-five healthy individuals that were matched with 25 hemodialysis patients in terms of gender and age wereincluded in the study. The IgM and IgG sero-prevalence in the patient and control groups wereinvestigated with theindirect fluorescence antibody method and HHV-6 DNA prevalence and the determination of variant types (variant Aand variant B) were investigated with the PCR-RFLP molecular method. HHV-6 IgG and HHV-6 IgM antibodypositivity ratios in the patient and control groups were 76% and 20% respectively. Out of 50 serum samples of hemodialysis patients and healthy individuals, HHV-6 DNA was positive in seven of 25 samples of hemodialysispatients (28%) and it was positive in eight of 25 samples of the control group (32%). Variant analysis was performedwith the PCR-RFLP method in HHV-6 DNA positive hemodialysis patients and control patients. At the end of theanalysis, while variant A was not detected in the patient and control groups, variant B was detected in a total of 15individuals, including seven patients in the hemodialysis patient group and eight patients in the control group. Inconclusion, the researchers believe that there is a need for controlled studies including more samples to determinethe clinical importance of HHV-6 DNA and HHV-6 variants in hemodialysis patients.

Human Herpes Virus 6 Infection in 54 Patients after Allogeneic Hematopoietic Stem Cell Transplantation: Clinical Manifestations and Outcome

▪BACKGROUND: Human herpesvirus type 6 (HHV-6) is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic hematopoietic stem cell transplantation (AlloSCT). HHV-6 is a member of the beta herpesvirus subfamily (genus Roseolovirus). HHV-6 infection is recognized as the cause of a febrile disease and exanthem subitum in early childhood. Approximately 60% of solid organ transplant and 40% of patients after alloSCT experienced HHV-6 reactivation. Reported clinical manifestations of HHV-6 infection in transplanted patients are skin rash, interstitial pneumonia, bone marrow suppression and encephalitis. Moreover, some clinical reports suggest that HHV-6 can facilitate the occurrence of severe clinical complications of alloSCT, increasing transplant-related mortality.METHODS: From January 2009 to February 2013, we retrospectively evaluated 54 consecutive adult patients (median age 50 years) who developed positivity to HHV-6 after alloSCT for high-risk hematological malignancies. Stem cell donors were family haploidentical (37), HLA identical sibling (8), unrelated volunteer (6), cord blood (3). The viral load was determined by quantitative PCR (Nanogen Advanced Diagnostic S.r.L) in cell-free body fluids such as plasma, bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), bone marrow (BM) aspirates or in gastrointestinal biopsies.RESULTS: Median time from alloSCT to HHV-6 reactivation was 34 days (range: 0-705). Thirty-one patients presented HHV-6 positive in plasma, 9/54 in BM, 33/54 in gut biopsies or BAL, 7/54 in CSF. At the time of viral positivity all pts were receiving acyclovir as viral prophylaxis except five. Twenty-nine patients had acute graft versus host disease (GvHD). Twenty-two out of these twenty-nine patients experienced a grade III-IV acute GvHD, requiring high dose steroids in twenty-six cases. A concomitant CMV positivity was detected in 15/54 patients. The median absolute count of CD3+ lymphocytes was 207 cells/mcl. In 52/54 cases we reported HHV-6 clinical manifestations: fever (43), skin rash (22), hepatitis (19), diarrhoea (24), encephalitis (10), BM suppression (18), delayed engraftment (11). HHV-6 positivity led to antiviral pharmacological treatment in 37/54 cases, using as first choice therapy foscarnet. Amongst the total fifty-four patients with documented HHV-6 positivity thirty-one solved the clinical event. However the mortality rate was relatively high in this population (overall survival (OS) ±SE at 1 year after HHV-6 reactivation was 38% ± 7%), mainly related to severe infections or GvHD.A better OS is significantly associated with CD3+ cells ≥200/mcl at the time of HHV-6 reactivation (fig 1) (OS at 1 year 63% compared to 11% for patients with CD3 <200/mcl; HR: 0.27, 95% CI 0.12-0.54, p=0.0002). The overall survival of these patients was also positively affected by the absence of acute GvHD grade III-IV at time of viral reactivation (HR: 0.03, 95% CI 1.08-4.03, p=0.03) and by the complete disease remission at time of HSCT (HR:0.26, 95% CI 0.07-0.89, p=0.03). In this analysis the overall survival was not significantly influenced by steroids administration (HR: 1.36, 95% CI 0.71-2.60, p=0.36), time after alloSCT (HR: 1.30, 95% CI 0.51-3.33, p=0.59), type of antiviral prophylaxis (HR: 1.02, 95% CI 0.45-2.33, p=0.96), plasma viral load (HR:1.18, 95% CI 0.51-2.76, p=0.69) and organ involvement (HR:1.14, 95% CI 0.59-2.20, p=0.70).CONCLUSIONS: This retrospective study confirms a correlation of HHV-6 with high morbidity and mortality rates after alloSCT, thus suggesting a regular HHV-6 monitoring in alloSCT recipients. The regular monitoring of HHV-6 DNA, using a real-time PCR assay, may be useful for identifying active HHV-6 infection and for the introduction of a pre-emptive treatment, possibly reducing the incidence of the most severe clinical complications. Despite HHV-6 detection typically occurred early after alloSCT, a better immune reconstitution has the potential to improve clinical outcome. [Display omitted] DisclosuresBonini:MolMed S.p.A.: Consultancy.

Congenital HHV-6 Infection: What Are the Neurodevelopmental Effects?

Human herpesvirus 6 (HHV-6), closely related to cytomegalovirus (CMV), infects most children in early childhood. Infection can be asymptomatic or can cause a nonspecific febrile illness or roseola infantum. Infection is associated with febrile seizures and can cause encephalitis in immunocompromised children. Like other herpesviruses, HHV-6 remains latent following primary infection and can become …

Serum levels of matrix metalloproteinase-9 and tissue inhibitor of metalloproteinases-1 in human herpesvirus-6-infected infants with or without febrile seizures.

Human herpesvirus-6 (HHV-6) is a cause of exanthema subitum and, sometimes, of febrile seizures. However, the pathogenesis of febrile seizures associated with HHV-6 infection remains unclear. We investigated serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) levels in infants with HHV-6 infection. Serum levels of both MMP-9 and TIMP-1 were significantly higher in infants with HHV-6 infection than in controls. Serum TIMP-1 levels were significantly higher in infants with febrile seizures than in infants without febrile seizures. Serum MMP-9/TIMP-1 ratios were significantly lower in infants with febrile seizures than in infants without febrile seizures. In infants with HHV-6 infection, positive correlations were found between serum MMP-9 concentrations and the white blood cells (WBC) count, and between serum TIMP-1 concentrations and the WBC count. Positive correlations were also found between the amounts of HHV-6 DNA and the ratios of MMP-9/TIMP-1 in infants with HHV-6 infection. In conclusion, we suggest that high serum levels of MMP-9 and TIMP-1 in infants with HHV-6 infection may induce dysfunction of the blood-brain barrier, eventually causing febrile seizures.

Detection of human herpesvirus 6 in cerebrospinal fluid of children with possible encephalitis.

Background:Encephalitis is swelling and inflammation of brain, usually due to viral infection. Viral encephalitis symptoms could be fever, headache, altered level of consciousness, and seizures.Objectives:The aim of this study was detection of human herpesvirus-6 (HHV-6) DNA in cerebrospinal fluid (CSF) of patients with symptoms of possible acute encephalitis and without typical signs or symptoms of roseola infantum, using real-time polymerase chain reaction (PCR).Patients and Methods:We studied children two years old or younger, admitted to the pediatric emergency ward with encephalitis-like symptoms. Our evaluation included detection of HHV-6 in CSF of these patients. After DNA extraction, real-time PCR was performed with primers and a probe specific for the U22 open reading frame of both HHV-6A and B.Results:From a total of 114 patients, HHV-6 was detected in 10 (8.8%), 90% of which were boys with mean age 7.7 months and median of 7.5 months. No significant differences were found in clinical presentations and laboratory findings between the patients positive and negative for HHV-6. All the children had complete recovery without neurological deficit or death.Conclusions:According to this research and prevalence of HHV-6 in children, evaluation of CSF (detecting the HHV-6 DNA by PCR) is recommended in patients younger than 13 months with possible encephalitis.

Roseola infantum and its causal human herpesviruses

Roseola infantum, also known as exanthem subitum or sixth disease, is a generally benign febrile exanthem of infancy. It has a characteristic clinical course of high fever followed by the appearance of an exanthem upon defervescence. Febrile seizures are a frequent complication. Roseola is caused by infection with human herpesviruses 6 or 7 (HHV-6/7), which are acquired at a young age. Diagnosis is made by serology or by virus detection in body fluids and tissues. Treatment of roseola is supportive; recovery is usually complete with no significant sequelae. However, HHV-6/7 can reactivate in immunocompetent as well as immunocompromised individuals with severe systemic consequence.

Case classification in measles surveillance system under the Two-level Logistic Model

To study the prevalence rates of Rash and Febrile Illnesses (RFIs) including measles, rubella, scarlet fever, exanthema subitum and the differences among measles and other RFIs to tentatively formulate the logistic regression model through clinical manifestation. All the suspected cases of measles, rubella, scarlet fever, exanthema subitum reported by the county/prefecture lever hospitals at four counties were collected during March 2011 to February 2012. When setting laboratory confirmed measles as dependent variable and existed symptoms as independent variable, a logistic regression model was formulated and optimal operational point (OOP)chosen, according to the ROC curve. A total number of 551 cases were collected but the consistency of measles diagnosis between clinical and laboratory was not satisfied, with Kappa value = 0.349, same to the diagnosis of rubella. As for the result from the two-lever logistic regression model, symptoms that related to the confirmation of measles would include cough (OR = 5.75), conjunctivitis (OR = 3.00), Koplik spot (OR = 7.52), lymphadenectasis(OR = 0.07), rash after fever (OR = 0.07). The area under ROC curve was 0.97 and the optimal operational point was 0.249. A logistic regression model was formulated using the clinical symptoms which was resulted in better performance on prediction. As the sample size of this survey was small, the expansion on the scale of investigation and laboratory testings were needed before the types and components of measles-related RFIs be clarified.

Quantification of two viral transcripts by real time PCR to investigate human herpesvirus type 6 active infection

BackgroundHuman herpesvirus 6 (HHV-6) causes exanthema subitum and is associated with symptomatic reactivations in immunocompromised patients, particularly after hematopoietic stem cell transplantation. The detection of viral mRNA can help to make the difference between latent, chromosomally integrated and true replicating virus. It can also be a useful tool to investigate viral multiplication in different cell types. ObjectivesTo develop molecular tools for the detection and quantification HHV-6 transcripts that can be used in a clinical setting. Study-designTwo one-step reverse-transcriptase quantitative real-time PCR (RT-qPCR) were developed for the quantification of the immediate early U90 and the late U100 mRNAs. Viral mRNA loads were compared to viral DNA loads during infection in vitro and in blood samples collected from stem cell transplanted patients. ResultsAnalytical performances of the two quantitative real-time PCR were good. In vitro, kinetics of both transcripts was well correlated with DNA levels. Sixty blood samples from patients with active HHV-6 infection were analyzed. Overall agreement of qualitative results for HHV-6 DNA, U90 RNA and U100 RNA was good. HHV-6 DNA loads were significantly higher than mRNA loads. In clinical samples, the amounts of U100 and U90 mRNAs were low and their detection was mainly associated to viral DNA loads upper than 1000copies/ml of blood. ConclusionThe new assays are sensitive and reliable methods for the monitoring of viral transcription in vitro and in vivo. As their detection is associated to high DNA loads in vivo, they can be helpful tools for the diagnosis of active infection.

Human Herpes Virus 6 Reactivation and Disease After Allogeneic Hematopoietic Stem Cell Transplantation

Background Human herpesvirus type 6 (HHV-6) is a member of the beta herpesvirus subfamily (genus Roseolovirus) and two distinct variants have been described: types A and B. HHV-6 infection is recognized as the cause of a febrile disease and exanthem subitum in early childhood. The infection rarely causes serious events in healthy individuals, but viral reactivation in immunocompromised patients is frequently associated with severe clinical manifestations. Above all HHV-6 is increasingly recognized as an opportunistic and potentially life-threatening pathogen in recipients of allogeneic hematopoietic stem cell transplantation (AlloSCT). Approximately 60% of solid organ transplant and 40% of patients undergoing alloSCT experience HHV-6 reactivation, mainly of variant B. Reported clinical manifestations of HHV-6 infection in transplanted patients are skin rash, interstitial pneumonia, bone marrow suppression and encephalitis. Moreover, some clinical reports suggest that HHV-6 can facilitate the occurrence of severe clinical complications of alloSCT, increasing transplant-related mortality. Methods From January 2009 to February 2013, we retrospectively evaluated 54 consecutive adult patients (median age 50 years) who developed positivity to HHV-6 after alloSCT for high-risk hematological malignancies. Stem cell donors were family haploidentical (37), HLA identical sibling (8), unrelated volunteer (6), cord blood (3). The viral load was determined by quantitative PCR (Nanogen Advanced Diagnostic S.r.L) in cell-free body fluids such as plasma, bronchoalveolar lavage (BAL), cerebrospinal fluid (CSF), bone marrow (BM) aspirates or in gastrointestinal biopsies. Results Median time from alloSCT to HHV-6 reactivation was 34 days (range: 0-705). Thirty-one patients presented HHV-6 positive in plasma, 9/54 in BM, 33/54 in gut biopsies or BAL, 7/54 in CSF. At the time of viral positivity all pts were receiving acyclovir as viral prophylaxis except five. Twenty-nine patients had acute graft versus host disease (GvHD). Twenty-two out of these twenty-nine patients experienced a grade III-IV acute GvHD, requiring high dose steroids in twenty-six cases. A concomitant CMV positivity was detected in 15/54 patients. The median absolute count of CD3+ lymphocytes was 262 cells/mcl. In 52/54 cases we reported HHV-6 clinical manifestations: fever (43), skin rash (22), hepatitis (19), diarrhoea (24), encephalitis (10), BM suppression (18), delayed engraftment (11). HHV-6 positivity led to antiviral pharmacological treatment in 37/54 cases, using as first choice therapy foscarnet. Amongst the total fifty-four patients with documented HHV-6 positivity thirty-one solved the clinical event. However the mortality rate was relatively high in this population (only 30% of patients were alive), mainly related to severe infections or GvHD. A better overall survival is significantly associated with CD3+ cells higher than 200/mcl (p-value 0.011) and time after alloSCT more than 2 months (p-value 0.035). In this analysis the overall survival was not significantly influenced by steroids administration, presence of acute GvHD, plasma viral load and organ involvement. Conclusions This retrospective study further demonstrates the correlation between HHV-6 reactivation and high morbidity and mortality rates in patients after alloSCT. Despite HHV-6 detection typically occurred in the first month after AlloSCT, a better immune reconstitution has the potential to improve the outcome. The regular monitoring of HHV-6 DNA, using a real-time PCR assay, may be useful for identifying active HHV-6 infection and for the introduction of a pre-emptive treatment, possibly reducing the incidence of the most severe clinical complications. Disclosures: Bonini: MolMed SpA: Consultancy.

Copy Numbers of Telomeric Repeat Sequences of Human Herpesvirus 6B in Clinical Isolates: Possibility of Mixed Infections

In order to determine whether mixed infections of human herpesvirus 6B (HHV-6B) occur in immunocompetent and immunocompromised individuals, we examined the copy numbers of telomeric repeat sequences (TRS) of clinical isolates. In clinical isolates obtained from patients with exanthem subitum caused by primary HHV-6B infection, PCR products with HHV-6B TRS ranging between 400 and 800 bp were amplified. PCR products of various sizes were amplified in four clinical isolates from drug-induced hypersensitivity syndrome (DIHS) patients and 15 isolates from hematopoietic stem cell transplant (HSCT) recipients with HHV-6B reactivation. Based on the sequence analysis of the PCR products, the copy numbers of TRS in DIHS and HSCT patients were between 42 and 82 and 22 and >90, respectively. For two of the HSCT recipients, HHV-6B TRS PCR products of different sizes were detected in several isolates from each patient, which suggests mixed HHV-6B infections. In two of the posttransplant HHV-6B encephalitis patients, the sizes of the TRS nested PCR products amplified from the reactivated virus detected in the central nervous system differed from those of the virus detected in initial isolates from peripheral blood mononuclear cells. Taken together, these results suggest that PCR analysis of TRS copy number is a reliable tool for the discrimination of HHV-6B clinical isolates. Additionally, mixed HHV-6B infections occurred in HSCT recipients, and in some cases, compartmentalization of the HHV-6B strains to the central nervous system versus the blood compartment occurred in posttransplant HHV-6B encephalitis patients.

Cytokine and chemokine responses in the blood and cerebrospinal fluid of patients with human herpesvirus 6B‐associated acute encephalopathy with biphasic seizures and late reduced diffusion

Acute encephalopathy with biphasic seizures and late reduced diffusion has become increasingly common among various types of human herpesvirus 6B (HHV-6B) encephalitis at the time of primary viral infection. The aim of the present study is to explore the pathophysiology of HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion. Five cytokines and five chemokines were measured in serum and cerebrospinal fluid (CSF) obtained from 12 HHV-6B-associated acute encephalopathy with biphasic seizures and late reduced diffusion patients and 19 control exanthem subitum (without complications) patients. Serum interleukin (IL)-10 (P = 0.007) and IL-8 (P = 0.025) were significantly higher in the patients with the disease than controls. Serum IL-1β (P = 0.034) and monocyte chemoattractant protein (MCP)-1 (P = 0.002) were significantly higher in the controls than patients with the disease. In patients with the disease, IL-10 (P = 0.012), regulated on activation normal T cell expressed and secreted (RANTES; P = 0.001), and monokine induced by interferon γ (MIG; P = 0.001) were significantly higher in serum than CSF, meanwhile IL-6 (P = 0.034), IL-8 (P = 0.034), and MCP-1 (P = 0.001) were significantly higher in CSF than serum. Additionally, serum IL-10 was significantly higher in the disease patients with sequelae than those without sequelae (P = 0.016). Several cytokines and chemokines may be associated with the pathogenesis of acute encephalopathy with biphasic seizures and late reduced diffusion. Moreover, the regulation of cytokine networks appears to be different between peripheral blood (systemic) and central nervous system.

Case Report: A rare cause of multiple organ dysfunction syndrome: Human Herpes Virus 6 infection

Human herpes virus 6 (HHV-6) is a member of the β-herpes virus subfamily which targets mainly CD4 T cells and is a well-known cause of roseola infantum. Fever without roseola, encephalitis and hepatitis however are not uncommon after HHV-6 infection. More severe clinical cases are commonly observed in immune compromised patients. Case: An 11-month old girl, after a 24-hour fever, and with poor appetite was admitted into the hospital. Oral antibiotic treatment was initiated and she was discharged from the state hospital’s out-patient clinic two hours later. The following day, the patient continued to experience high fever, and hematemesis, and a tendency to sleep were added to her condition and she was once more admitted to the hospital. Lab results showed thrombocytopenia, alanine aminotransferase over 3000 U/L, INR was 2.5 and urea and creatinine were elevated at 75 mg/dl and 1.1 mg/dl, respectively. Due to persistent high fever and somnolence, a lumbar puncture was performed. The cerebrospinal fluid (CSF) was clear of any cells; protein and glucose were within normal range. However, test results were positive for HHV-6 DNA in the CSF, serum, and lymphocytes. Four organ dysfunctions including the central nervous-, hematologic-, renal- and hepatic systems, developed because of HHV-6 infection. Organ functions were normalized within one week of supportive treatment. HHV-6 is a benign virus that very rarely causes severe infection and hardly ever leads to a fatal infection. However, in our case, a healthy child, with a HHV- viral infection led to multiple organ dysfunction without any predisposing reason.

Diagnosing rashes, part 4: Generalized rashes with fever

Practice NursingVol. 24, No. 7 DermatologyDiagnosing rashes, part 4: Generalized rashes with feverJean WatkinsJean WatkinsSearch for more papers by this authorJean WatkinsPublished Online:29 Sep 2013https://doi.org/10.12968/pnur.2013.24.7.335AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View articleReferencesChen S (2011) Measles, http://tinyurl.com/d8wrhzs (accessed 3 June 2013) Google ScholarChiang N, Verbov J; British Association of Dermatologists (2009) Dermatology: A handbook for medical students and junior doctors, http://tinyurl.com/bpoatm4 (accessed 3 June 2013) Google ScholarDermNet NZ (2011) Meningococcal disease, http://tinyurl.com/karg49a (accessed 3 June 2013) Google ScholarGP Notebook (2013) Antistreptolysin O titre. http://tinyurl.com/m6ezmqk (accessed 3 June 2013) Google ScholarHealth Protection Agency (2010a) List of notifiable diseases, http://tinyurl.com/ccnkn48 (accessed 3 June 2013) Google ScholarHealth Protection Agency (2010b) Guidance on infection control in schools and other childcare settings. http://tinyurl.com/7abl364 (accessed 3 June 2013) Google ScholarLombardo P (2011) Dermatological manifestations of rubella, http://tinyurl.com/n8xmkqt (accessed 3 June 2013) Google ScholarMeningitis Trust (2013) Meningitis B vaccine now one step closer. http://tinyurl.com/lvmtdjp (accessed 3 June 2013) Google ScholarOakley A (2012) Nonspecific viral exanthems. http://tinyurl.com/6stuql6 (accessed 3 June 2013) Google ScholarPapadopoulos A (2012) Chickenpox. http://tinyurl.com/mnl8m7p (accessed 3 June 2013) White S (2013) Roseola infantum. http://tinyurl.com/n88dxue (accessed 3 June 2013) Google Scholar FiguresReferencesRelatedDetails 1 July 2013Volume 24Issue 7ISSN (print): 0964-9271ISSN (online): 2052-2940 Metrics Downloaded 14 times History Received 3 June 2013 Accepted 25 June 2013 Published online 29 September 2013 Published in print 1 July 2013 Information© MA Healthcare LimitedKeywordsGeneralized rashesfeverinfectious illnessessymptomsdiagnosisPDF download

The Long-Term Outcomes of Patients Transplanted Due to Acute Liver Failure With Hepatic Human Herpesvirus-6 Infection

Human herpesvirus (HHV)-6, comprised of HHV-6A and HHV-6B, belongs to the betaherpesviruses that infect 95%–100% of humans. Primary infection, known as exanthema subitum, occurs in early childhood. Reactivations of latent HHV-6, mostly HHV-6B, are common after liver transplantation. The vast majority of them are asymptomatic; in a minority of cases, the virus may infect the liver transplant, causing graft dysfunction or hepatitis. An association between hepatic HHV-6 infection and indeterminate acute liver failure (ALF) has been shown, but the causality is not clear because of the ubiquitous nature of HHV-6. We have previously observed HHV-6B antigens in the explanted livers of most patients (80%, n = 32) transplanted with ALF of unknown cause, whereas it was not observed among those with ALF of known cause. After transplantation, half of the patients with pretransplant HHV-6 infection (9/18) developed recurrences. The aim of this study was to investigate their long-term course (9–14 years). Half of the patients with pretransplant HHV-6 developed recurrences. Two also showed cytomegalovirus (CMV) hepatitis, whereas none of the other patients demonstrated intrahepatic CMV. During the 9 years or more of follow-up, 1 graft and 2 patients were lost in both groups (HHV-6 recurrence/HHV-6-negative patients). The reasons for graft loss were hepatic arterial thrombosis and portal venous thrombosis. In addition 2 patients died in the HHV-6 recurrence group, one because of rethrombosis of hepatic artery (day 460) and one with a functioning transplant (4.5 years after transplantation). In the control group 1 patient died at 1.5 years and 1 at 10 years after liver transplantation because of pneumonia. HHV-6 relapse was common in ALF patients after transplantation. However, HHV-6 did not cause liver failure and had no significant long-term effect on survival.