Human Herpesvirus 6 DNA Research Articles

Incidence and relationship of human cytomegalovirus infection and human herpesvirus 6 infection in pediatric patients after hemopoietic stem cell transplantation

To study the incidence of human cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6) infection in pediatric patients with hemopoietic stem cell transplantation (HSCT), and to explore the relationship between CMV and HHV-6 infection in pediatric patients with HSCT. Pediatric patients with HSCT in hemotology center of Beijing Children's Hospital were enrolled into this study from June 2007 to October 2009. Peripheral blood were collected every week after HSCT, and Fluorescent quantitation PCR and conventional PCR were used to detect CMV DNA load in serum and HHV-6 DNA in peripheral blood respectively. Genetic typing was conducted on HHV-6. Fifty two pediatric patients with HSCT were enrolled into this study, and six hundreds and thirty six specimens were collected totally. CMV DNA was detected in fifty two specimens from twenty cases. The median time was 56 days after HSCT. The incidence of CMV infection was 38.5% (20/52) in all HSCT patients and 47.6% (20/42) in allogene HSCT patients. The incidence of late CMV infection was 22.2% (6/27) in allogene HSCT. Three patients died of CMV infection,and two died of CMV interstitial pneumonia. HHV-6 DNA was detected in thirty three specimens from fourteen cases. The median time was 23 days after HSCT. The incidence of HHV-6 infection was 26.9% (14/52)in all HSCT patients and 31% (13/42) in allogene HSCT patients. The genotype of HHV6 was all type B. HHV-6 DNA was positive in six of twenty cases with CMV infection. The incidence of co-infection was 30% (6/20). There was a substantial incidence of CMV and HHV6 infection after HSCT. The relationship between earlier HHV6 infection and later CMV infection in pediatric patients with HSCT need further study.

PCR detection of multiple human herpesvirus DNA in saliva from HIV-infected individuals in Teresina, State of Piauí, Brazil

Human herpesviruses are frequently associated with orofacial diseases in humans (HSV-1, EBV, CMV and HHV-8), some can also cause systemic disease (CMV and HHV-8). The transmission of these viruses occurs by contact with infected secretions, especially saliva. Human immunodeficiency virus infection is associated with an increased risk of HHVs and related diseases. This work aimed to detect HSV-1, EBV, CMV and HHV-8 DNA in saliva of HIV-infected patients from Teresina, northeast Brazil, by PCR and compare these findings with age and sex matched HIV-seronegative individuals. No difference in prevalence was verified between HHV detection in the saliva of HIV-seropositive individuals and controls. The individual frequencies of these viruses in these two populations were different. HIV seropositivity correlated positively with the presence of CMV (OR: 18.2, p= 0.00032) and EBV (OR: 3.44, p= 0.0081). No association between CD4 counts and the prevalence of HHVs in the saliva was observed; however, a strong association was determined between seropositivity and the presence of multiple HHV DNAs in saliva (OR: 4.83, p = 0.0028). These findings suggest the asymptomatic salivary shedding of HHVs is a common event between HIV-seropositive and seronegative individuals from Teresina, Piauí, Brazil, and, especially for HIV-seropositive patients, saliva is a risk factor for the acquisition/transmission of multiple HHVs.

Presence of Human Herpes Virus 6 (HHV6) in pediatric lymphomas: impact on clinical course and association with cytomegalovirus infection

BackgroundActivation of herpes virus 6 (HHV6) has seen in Hodgkin's and non-Hodgkin's Lymphoma (HL&NHL) as a result of lymphoma associated immunosuppression. Multiple studies have suggested an association between both HHV6 and cytomegalovirus CMV for development of CMV disease affecting the pathogenesis of lymphoma. Therefore, this study investigated the frequency of HHV6, its impact on clinical manifestations of lymphoma and its possible association with risk for development of CMV infection in pediatric lymphoma patients.MethodsPresence of HHV6 DNA and CMV DNA was investigated by PCR assay in both WBC's and plasma samples from 50 patients diagnosed with HL or NHL. CMV antibody titer was also determined in sera obtained from each patient. Twenty apparently healthy siblings were used as a control group.ResultsIn a study group of 50 patients diagnosed with HL or NHL, 23/50 (46%) were found to be positive for herpes virus DNA (HHV6 or CMV) in WBC's or plasma by PCR assay and this was significantly higher than its presence in the pediatric control group 2/20 (10%) (p = 0.005). Ten out of these 23 (43%) were found to have active CMV infection. Fifty six percent of patients with CMV infection were found among NHL cases with B- subtype. The presence of both herpes viruses DNA was significantly associated with more frequent episodes of febrile neutropenia (median 3 episodes), absolute neutrophil count (< 0.8), lymphocytes (< 0.5), and low hemoglobin level (< 9.1), (p < 0.05).ConclusionThe presence of HHV6 can be considered as a predicting indicator of cellular immunosuppression preceding the onset of CMV infection which may result in a severe outcome among pediatric lymphoma patients.

Salivary shedding of HHV-8 in people infected or not by human immunodeficiency virus 1

Human herpesvirus 8 (HHV-8), the main agent involved in the etiopathogenesis of Kaposi's sarcoma (KS) is primarily transmitted through sexual contact. The potential of saliva as a source of HHV-8 transmission remains unclear. The purpose of this work was to determine the frequency of HHV-8 detection in saliva of HIV-infected individuals and their family contacts. The study group comprised 210 individuals. Group 1: 35 HIV-infected patients; group 2: 35 non-HIV individuals; group 3: two siblings for each patient from group 1; group 4: two siblings for each individual from group 2. Each participant had non-stimulated whole saliva collected and DNA was extracted. HHV-8-DNA amplification from ORF-26 was performed using a nested PCR protocol. HHV-8 DNA was detected in saliva from 14/35 (40%) HIV-infected individuals and 4/35 (11.4%) non-HIV-infected individuals (OR = 5.16, CI [1.49-17.88], P = 0.006). It was also possible to amplify HHV-8 DNA in 11/70 (15.7%) relatives of HIV-infected participants and 4/70 (5.71%) relatives of non-HIV-infected individuals(P = 0.041). Among the 14 group 1 patients with HHV-8 DNA detected in saliva, eight (57.1%) had a household member in whom HHV-8 DNA was also amplified (OR = 8, CI [1.58-40.29] P = 0.007). HHV-8 DNA is frequently found in saliva. HIV-infected individuals showed a higher frequency of detection of HHV-8 than healthy controls. HHV-8 DNA was significantly amplified in saliva of household members of HIV/HHV-8 co-infected individuals.

Pemphigus vulgaris and herpesviruses: is there any relationship?

Pemphigus is an autoimmune disorder, which results from interaction of exogenous and endogenous factors. One of these environmental factors is viral infections particularly, herpesviruses. We aimed to detect the presence of HSV 1 and 2 (herpes simplex virus) and HHV8 (human herpesvirus 8) in our patients who were suffering from pemphigus vulgaris. In this cross-sectional study, 38 patients (19 male and 19 female patients) with pemphigus vulgaris were entered, 32 skins and six peripheral blood cells samples were obtained from the study population. Thereafter, the presence of HHV8 and HSV DNA were evaluated by using polymerase chain reaction (PCR). The mean age of patients was 45.05 ± 17.24 years (range: 16-81 years). Twelve patients mentioned history of herpes labial in the past (31.57%). Results of PCR test for detection of HSV and HHV8 DNA in all 32 skin samples and five peripheral blood samples and one case with skin and blood samples were reported negative. Inability to detect HHV8 and HSV DNA in this study suggests that herpesviruses may be only occasional factors for development or exacerbation of pemphigus vulgaris.

The role of human herpesvirus‐6, Epstein–Barr virus and cytomegalovirus infections in the etiopathogenesis of different types of cutaneous drug reactions

Recently, it has been recognized that drug-induced hypersensitivity syndrome (DIHS) is associated with reactivation of human herpesvirus-6 (HHV-6), Epstein–Barr virus (EBV) and cytomegalovirus (CMV). However, whether those viruses have a role in the development of cutaneous drug reactions (CDRs) other than DIHS is not known. To investigate the role of HHV-6, EBV and CMV infections in the etiopathogenesis of different types of CDRs. Eighteen patients with diagnosis of CDR according to the clinical and histopathological findings were evaluated. Real-time polymerase chain reaction (PCR) was used for the detection of EBV, CMV, and HHV-6 DNA in lesional skin biopsy specimens; EBV and CMV DNA in serum samples; and HHV-6 DNA in peripheral blood mononuclear cells. The genome of HHV-6 was detected only in the lesional skin of two patients with DIHS. Epstein–Barr virus and CMV DNA in the skin lesions, EBV and CMV genomes in the serum samples, and HHV-6 DNA in the peripheral blood mononuclear cells were negative in all patients. The patient population was small and did not include all types of CDRs. Also, we had only two patients with DIHS. We had not been able to measure the increase in anti-viral IgG titers in serial serum samples. Epstein–Barr virus and CMV infections do not seem to have a role in the etiopathogenesis of CDRs including DIHS. The association between HHV-6 infection and CDRs is likely to be limited to DIHS.

Presence of human herpes virus 6 DNA exclusively in temporal lobe epilepsy brain tissue of patients with history of encephalitis

Temporal lobe epilepsy (TLE) is frequently associated with mesial temporal sclerosis (MTS). Many etiologic aspects of TLE are still unresolved. Here, we aimed to analyze the presence of human herpes virus 6 (HHV-6) DNA in distinct TLE pathologies. Nested polymerase chain reaction (PCR) in surgical tissue from 38 pharmaco-resistant TLE patients and 10 autopsy controls revealed HHV-6 DNA in 55.6% of the TLE patients with a history of encephalitis, involving MTS and gliotic hippocampi without substantial neurodegeneration, but not in lesion-associated TLE or nonlesional MTS with or without a history of complex febrile seizures (CFS). HHV-6 protein was present in only one patient's tissue. Our data argue against HHV-6 as a major local pathogenetic factor in MTS hippocampi after CFS. The high detection rate of HHV-6 DNA suggests a potential pathogenetic role of HHV-6 in TLE patients with a history of encephalitis.

Detection of Human Herpesvirus 6 DNA but not Human Herpesvirus 7 or 8 DNA in Atherosclerotic and Nonatherosclerotic Vascular Tissues

Various viral infections are thought to play a role in the development of atherosclerosis. A number of studies suggest that certain viruses from the Herpesviridae family in particular may lead to atherosclerosis. We investigated the presence of human herpesvirus 6 (HHV-6), human herpesvirus 7 (HHV-7), and human herpesvirus 8 (HHV-8) DNA in carotid, iliac, and coronary artery specimens obtained from a group of adult autopsy cases by means of polymerase chain reaction (PCR) analysis and nested PCR techniques. A 28-subject study group with at least type IV atherosclerosis and a 25-subject control group with no visible atherosclerosis were enrolled. HHV-6 DNA was found in the carotid artery specimen of 1 subject with atherosclerosis, in an iliac artery specimen of another subject, and in the iliac artery specimen of one of the control subjects. HHV-7 or HHV-8 DNA was not found in either the atherosclerosis or control cases. This study is the first to demonstrate the presence of HHV-6 in atherosclerotic vascular tissues. HHV-7 and HHV-8 were not found in atherosclerotic tissues; however, further research on broader study groups and with different protocols is needed to determine whether these viruses play a role in the formation of atherosclerosis.

Infections aiguës à herpèsvirus humain 6 (HHV-6) : quand et comment traiter ?

The pathogenicity of human herpesvirus 6 (HHV-6) still raises numerous questions. Acute HHV-6 infections correspond to primary infections, reactivations or exogenous reinfections. The expression of related clinical symptoms is highly variable but may be extremely severe, particularly among immunocompromised patients. The prototypic severe disease associated with these infections is limbic encephalitis occurring in stem cell transplant recipients. The diagnosis of acute HHV-6 infections relies on the quantitation of viral load in whole blood by means of quantitative PCR. The demonstration of HHV-6 causative role in the genesis of clinical symptoms requires additional investigations such as the search for HHV-6 DNA in cerebrospinal fluid in case of encephalitis. The chromosomal integration of HHV-6 DNA is a rare event among HHV-6-infected subjects but may alter the interpretation of virological results. Therapy with ganciclovir, foscarnet or cidofovir has not yet clear indications but, at the current stage of knowledge, only concerns the treatment of highly symptomatic infections. The usefulness of prophylactic or pre-emptive antiviral chemotherapy has not yet been convincingly demonstrated. Treatment efficacy must be checked through a clinical and virological follow up, based in part on quantitative PCR approaches. Controlled studies are urgently needed with the goal of evaluating the cost-effectiveness of HHV-6 follow up and therapy in different clinical situations.

Preemptive therapy of human herpesvirus-6 encephalitis with foscarnet sodium for high-risk patients after hematopoietic SCT

Human herpesvirus-6 (HHV-6) is a major cause of limbic encephalitis with a dismal prognosis after allogeneic hematopoietic SCT (HSCT). A prospective, multicenter study was conducted to assess the safety and efficacy of preemptive therapy with foscarnet sodium (PFA) for the prevention of HHV-6 encephalitis. Plasma HHV-6 DNA was measured thrice weekly from day 7 until day 36 after umbilical cord blood transplantation (UCBT) or HSCT from HLA-haploidentical relatives. PFA, 90 mg/kg/day, was started when HHV-6 DNA exceeded 5 × 10(2) copies/mL. Mild and transient adverse events were associated with PFA in 7 of 8 patients. Twelve of 15 UCBT recipients became positive for HHV-6 DNAemia, defined by greater than 1 × 10(2) copies/mL of HHV-6 DNA in plasma. The virus exceeded 5 × 10(2) copies/mL in seven patients, whereas none of the five HLA-haploidentical HSCT recipients became positive. One patient developed mild limbic encephalitis just after initial PFA administration. Preemptive PFA therapy is safe, but as HHV-6 DNAemia can abruptly develop before neutrophil engraftment in UCBT recipients, prophylactic PFA administration from day 7 or earlier after UCBT may be needed.

Detection of HHV-8 (human herpesvirus-8) genomes in induced peripheral blood mononuclear cells (PBMCs) from US blood donors

Human herpesvirus-8 (HHV-8) causes Kaposi's sarcoma and can be detected and induced in peripheral blood mononuclear cells (PBMCs) from infected individuals. The prevalence of viral genomes in induced/cultured PBMCs from healthy blood donors has not been systematically studied. PBMCs from 164 donors were purified and stored as two equal aliquots in liquid nitrogen. One aliquot was used for CD19+ B-cell purification with a fraction reserved for DNA extraction. The second aliquot was cultured for 2 or 4 days in culture media containing n-butyrate and tetradecanoyl phorbol acetate. DNA was extracted from all four cell sources: PBMCs, purified B cells, induced PBMCs harvested at days 2 and 4 of culture. A sensitive real-time PCR with a DNA equivalent of 3×10(5) cells per reaction was run in duplicate for all samples along with a quantitative HHV-8 DNA standard ranging from 1.6 to 200 copies. For all 164 donors, HHV-8 genomes were not detected in the DNA equivalent of 3-6×10(5) of PBMCs and induced/cultured PBMCs with a real-time PCR assay (95% CI: 0-3.5/164). HHV-8 DNA was not detected from DNA equivalent of 1.5 (0.5-5.6)×10(5) CD19+ B cells from 139/164 donors. HHV-8 antibodies were detected in 7 of the 164 donors (4.3%). HHV-8 genomes were not detected from PBMCs, induced/cultured PBMCs and CD19+ B cells from 164 blood donors. The level of detectable HHV-8 genomes in blood donors seems to be extremely low, if they exist.

IgG subclasses and DNA detection of HHV‐6 and HHV‐7 in healthy individuals

Human herpesvirus 6 (HHV-6) and 7 (HHV-7) are common opportunistic agents in immunocompromised hosts, although infection with HHV-6 and HHV-7 can also be observed in immunocompetent hosts. Despite similar biology and epidemiology, this study evaluated differences in the IgG subclass distribution associated with HHV-6 and HHV-7 in seropositive, healthy persons. The identified subclasses were also compared with the detection of HHV-6 and HHV-7 DNA. For these assays, sera, plasma, and saliva samples were obtained from 40 healthy blood donors in Argentina who were seropositive for both HHV-6 and HHV-7. HHV-6 and HHV-7 DNA were detected in saliva and plasma samples using nested PCR, and specific IgG subclasses were determined using immunofluorescent assays of sera samples. HHV-7 DNA was detected in 90% of all plasma samples and in 100% of saliva samples. In contrast, HHV-6 DNA was not detected in any of the plasma samples, and it was detected in only 6 of 40 saliva samples. Determination of IgG subclass distributions showed that HHV-6 was restricted to IgG1, whereas HHV-7 IgG subclasses included two groups, one restricted only to IgG1 and the other to IgG1 and IgG3. These results demonstrate the differences between HHV-6 and HHV-7 DNA range detection in saliva and plasma samples, as well as the IgG subclass patterns for each virus type, in healthy persons in Argentina.

Review part 2: Human herpesvirus‐6 in central nervous system diseases

AbstractJ. Med. Virol. 82:1669–1678, 2010. © 2010 Wiley‐Liss, Inc.

Human Herpesvirus 7 in Allogeneic Hemopoietic Stem Cell Transplant Recipients in the Central Clinical Hospital in Warsaw: A Three-Year Survey

Objectives: Human herpesvirus 7 (HHV-7) is spread worldwide and has been described as a potential pathogen in immunosuppressed patients. Different clinical manifestations have been described including fever and skin rash; HHV-7 may also be a possible cofactor for cytomegalovirus disease in transplant recipients. Materials and Methods: A retrospective review of a group of 58 adult recipients of allogeneic hemopoietic stem cell transplantation was made. Serum samples taken in the range of 0–180 days after transplant were examined for presence of specific HHV-7 sequences using the quantitative real-time PCR method. Results: HHV-7 DNA was detected in plasma samples in 26 (45%) of the 58 recipients between day 20 and day 65 of transplantation. All of them developed fever of unknown origin; also HHV-5 DNA was detected in plasma samples collected from 11 HHV-7-positive patients. None of the described individuals died during detectable HHV-7 or HHV-5 viremia periods. Conclusions: There is a high frequency of detectable HHV-7 viral load in allogeneic stem cell transplant recipients in Poland. Limited availability and sensitivity of serological methods along with the necessity of rapid introduction of antiviral treatment has forced the development of molecular diagnostics. Furthermore, establishment of appropriate procedures for monitoring active HHV-7 infection is important to clarify the virus infection in transplant recipients.

Evaluation of Plasma Human Herpesvirus 8 DNA as a Marker of Clinical Outcomes during Antiretroviral Therapy for AIDS‐Related Kaposi Sarcoma in Zimbabwe

The usefulness of plasma human herpesvirus 8 (HHV-8) DNA as a marker of response to treatment for acquired immunodeficiency syndrome-associated Kaposi sarcoma (AIDS-KS) in an African setting is unknown. We conducted a prospective pilot study at the Parirenyatwa Hospital Kaposi Sarcoma Clinic (Harare, Zimbabwe) to investigate the hypothesis that the clinical response of AIDS-KS is associated with suppression of HHV-8 DNA. Antiretroviral therapy (ART) was provided as coformulation of abacavir, lamivudine, and zidovudine. Clinical response was defined as survival to week 96 with either complete or partial resolution of KS disease. Ninety ART-naive participants (62 men and 28 women) aged >18 years who had human immunodeficiency virus type 1 (HIV-1) infection and biopsy-confirmed KS were studied; 82% had stage T1 disease. Fifty participants received adjunctive chemotherapy. The median CD4(+) lymphocyte count increased from 124 cells/microL at baseline to 281 cells/microL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log(10) copies/mL, the plasma HHV-8 DNA level decreased from 660 to <25 copies/mL, and HHV-8 DNA level in peripheral blood mononuclear cells decreased from 2790 to 37 copies/10(6) cells (P < .001 for each comparison). There were 14 deaths (16%) and 13 patients (15%) lost to follow-up. The most common cause of death was infection. Clinical response of KS occurred in 17 participants (19%). Pretreatment plasma HHV-8 DNA levels of <660 copies/mL were associated with greater survival (odds ratio, 2.83; 95% confidence interval, 1.07-7.53; P = .04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; P = .006). AIDS-KS tumor responses after ART initiation were limited. Pretreatment plasma HHV-8 DNA level may be a surrogate for KS disease that is in need of intensive clinical management.

The prevalence of antibodies to human herpesvirus 8 and hepatitis B virus in patients in two hospitals in Tanzania

The aim of this study was to determine the seroprevalence of human herpesvirus 8 (HHV-8) and the immunization status for hepatitis B virus (HBV) infection in febrile patients in two districts of the United Republic of Tanzania. Between February and March 2007, blood samples were collected in Pemba Island and Tosamaganga from 336 outpatients and sent to the Virology Laboratory in Rome (Italy) for testing. HHV-8 DNA and HBV-DNA were amplified by two in-house molecular methods, anti-HHV-8 antibody titers were determined by an immunofluorescence assay (IFA), and anti-HCV, HBsAg, anti-HBs, and anti-HBc were evaluated by microplate enzyme immunoassay (MEIA). The seroprevalence of HHV-8 was 30.7% (96/313). In Pemba Island, the prevalence was lower than in Tosamaganga (14.4% vs. 46.3%). A higher prevalence of low titers of HHV-8 IgG (<1:80, 81%) was found among those under 5 years of age. HHV-8 DNA was detected in six seropositive patients (6.7%). The prevalence of HBsAg, anti-HBs, and anti-HBc was 4.3%, 37.6%, and 29.3%, respectively. Out of 277 patients, 70 had had a previous infection (25.3%). One case of occult hepatitis was found. The cover of hepatitis B vaccination was higher among children born after 2002 (66.7%) than in patients born before 2002. HHV-8 infection is endemic in Tanzania and the seroprevalence rate was higher in the mainland than on Pemba Island. The 3.9% percentage of HBsAg in children younger than 4 years of age suggests that increased efforts are required in order to achieve universal and compulsory immunization of children against HBV.

Translational Challenges Of Human Herpesvirus 6 Chromosomal Integration

Translational Challenges Of Human Herpesvirus 6 Chromosomal Integration

Comparison of the levels of human herpesvirus 6 (HHV‐6) DNA and cytokines in the cerebrospinal fluid and serum of children with HHV‐6 encephalopathy

Primary human herpesvirus-6 (HHV-6) infection is a common cause of acute sporadic encephalopathy in Japanese children. Occasionally, HHV-6 is not detected in the cerebrospinal fluid (CSF) of patients with encephalopathy, for example, in those with focal viral encephalitis, such as herpes simplex viral encephalitis. This indicates that HHV-6 encephalopathy is caused by an indirect mechanism, although this is not fully understood. HHV-6 DNA, cytokines (interleukin (IL)-1beta, IL-6, IL-8, IL-10, IL-12 p70, tumor necrosis factor-alpha, interferon-gamma), and matrix metalloproteinase-9 were quantitated in both the CSF and serum of 13 patients with HHV-6 encephalopathy during the acute phase of the disease. HHV-6 DNA was detected in the CSF of seven patients with HHV-6 encephalopathy. The viral DNA concentration was significantly higher in serum than in CSF (mean 1.64 x 10(4) vs. 5.70 x 10(1) copies/ml; P = 0.003). The lack or low level of viral DNA in the CSF samples suggests that direct invasion of the central nervous system by HHV-6 is not the main cause of encephalopathy. Additionally, the IL-10 concentration was significantly higher in serum than in CSF (P < 0.001), whereas there was no significant difference in IL-6 levels between the CSF and serum samples. Interestingly, the IL-8 concentration was significantly higher in CSF than in serum (P = 0.038). The distribution of these cytokines differed between CSF and serum. The high CSF concentration of IL-8 could play an important role in the pathogenesis of encephalopathy.

Human herpesvirus 6-related pure red cell aplasia, secondary graft failure, and clinical severe immune suppression after allogeneic hematopoietic cell transplantation successfully treated with foscarnet

Human herpesvirus 6 (HHV-6) is frequently detected after allogeneic hematopoietic cell transplantation (allo-HCT); however, the clinical interpretation of HHV-6 viremia in a transplant patient is challenging as it may signify asymptomatic reactivation, chromosomal integration of the virus genome in the donor or recipient with no clinical significance, or severe HHV-6 disease. Here we present a case of HHV-6 disease after allo-HCT presenting as pure red cell aplasia, secondary graft failure, and severe immunosuppression causing multiple severe bacterial super-infections. Examination of pre-transplant patient and donor samples as well as serial determination of HHV-6 DNA copy numbers after transplantation were necessary to definitively interpret HHV-6 viremia as active HHV-6 infection with a causative role in pancytopenia and immune suppression. Foscarnet treatment resulted both in viral load decline and disappearance of HHV-6-related bone marrow suppression and predisposition to severe infections. Clinicians should be aware of the wide array of clinical manifestations and the diagnostic pitfalls of post-transplant HHV-6 disease. These issues are extremely challenging, as they may result either in dangerous underestimation of HHV-6 disease or in the institution of unnecessary antiviral therapy. Late bone marrow aplasia and late severe infections after allo-HCT without other obvious causes may be HHV-6 related.

High-Dose Ganciclovir in HHV-6 Encephalitis of an Immunocompetent Child

Encephalitis and other neurologic complications, including acute necrotizing encephalopathy, are associated with human herpesvirus-6 infection. Antiviral treatment against human herpesvirus-6 infection is indicated only for immunocompromised patients. We describe a 15-month-old immunocompetent child with severe human herpesvirus-6-induced encephalitis. The primary infection was characterized by human herpesvirus-6 DNA in cerebrospinal fluid and serum, the presence of serum human herpesvirus-6 immunoglobulin M antibodies, and a rise in serum human herpesvirus-6 immunoglobulin G antibodies. Magnetic resonance imaging demonstrated multiple, partly symmetric, necrotic lesions in the pons, medulla oblongata, thalamus, external capsules, and occipital subcortical and cortical areas. High-dose ganciclovir (18 mg/kg/day) was used as antiviral treatment, without side effects. A pharmacokinetic analysis of ganciclovir was performed. The initial recovery from severe disease was good. At 3-year follow-up, neurologic sequelae included epilepsy and ataxia. This case suggests that treatment with ganciclovir should be considered in human herpesvirus-6 central nervous system infections because the neurologic sequelae may otherwise be severe. Controlled, prospective, clinical trials are warranted, to analyze the pharmacokinetics of ganciclovir in infants.