Primary Human Herpesvirus-6 Infection Research Articles

Disseminated Pulmonary Kaposi Sarcoma After Lung Transplantation: The Increased Risk Donor

<h3>Introduction</h3> Kaposi sarcoma (KS) is a rare complication after lung transplantation (LTx). It is caused by human herpes virus 8 (HHV-8). We report a case of primary disseminated pulmonary KS after LTx from an increased risk donor. <h3>Case Report</h3> A 66-year-old male with end-stage COPD underwent a bilateral LTx from an increased risk donor with positive HBsAb, HBcAb and Lues Ab, in November 2020. Apart from Valganciclovir (vGCV) and co-trimoxazole, entecavir and benzylpenicillin were given as prophylaxis. Routine immunosuppression included basiliximab, tacrolimus, mycophenolate mofetil (MMF) and prednisolone. vGCV prophylaxis was discontinued at 3 months (CMV-positive donor and recipient). The patient was treated effectively for acute rejection with pulse methylprednisolone in February 2021. Unfortunately, he was readmitted with dyspnea and lung function decline in April 2021. CT-scan showed bilateral consolidations and pleural thickening and the PET-scan showed an intense uptake in both lungs and pleura. Transthoracic needle biopsy showed HHV-8 positive spindle cell lesions. Subsequently, our patient developed skin lesions on his chest and in his mouth compatible with KS (biopsy-proven). In retrospect, the recipient was HHV-8 seronegative before LTx. Therefore, the diagnosis primary HHV-8 infection leading to disseminated pulmonary Kaposi sarcoma was made. Which appeared after cessation of the vGCV prophylaxis. Valganciclovir was initiated and immunosuppression was adjusted: MMF discontinued and tacrolimus switched to sirolimus (target through levels 15 µg/l). Nevertheless, KS was progressive and liposomal doxorubicin 20mg/m2 was started. Our patient deteriorated and was transferred to the ICU for intubation. Bronchoscopy revealed brown endobronchial lesions compatible with KS. The effect of the treatment could not be assessed, because the patient decided to refuse further treatment. He died soon after his decision was made. <h3>Summary</h3> Scarcity of donor organs led to the acceptance of an increased risk donor. Prophylaxis against hepatitis B and Lues was given, but after discontinuation of vGCV our patient developed a primary HHV-8 infection leading to disseminated KS and ultimately the death of our patient. HHV-8 testing of donor serum and lifelong prophylaxis might have prevented this clinical course and should be considered in recipients of increased risk donors.

Hemolytic uremic syndrome related to Shiga-like toxin-producing Escherichia coli with encephalitis hiding a human herpesvirus-6 infection: a case report

BackgroundCardiac and neurological involvement in hemolytic uremic syndrome are life-threatening complications. The most frequent complications of cardiac involvement in hemolytic uremic syndrome are myocarditis and cardiac dysfunction due to fluid overload. Pericarditis remains very rare in hemolytic uremic syndrome. To our knowledge, only five cases of cardiac tamponade associated with hemolytic uremic syndrome have been described in literature.Case summaryA 27-month-old Caucasian girl presented with symptoms of nonbloody diarrhea and tonic-clonic seizures. The diagnosis of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome with central nervous system involvement was made, and stool examination revealed infection with a Shiga-like toxin-producing Escherichia coli. She did not need renal replacement therapy but had severe neurological impairment. The patient’s course was complicated by pericardial effusion. A pericardiocentesis was performed via an apical approach because the pericardial effusion was predominantly surrounding the left ventricle. Effusion analysis showed an exudate and positivity for human herpesvirus-6B on polymerase chain reaction with viremia. This finding was consistent with primary human herpesvirus-6 infection with encephalitis.ConclusionWe report this uncommon case of Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome associated with a severe human herpesvirus-6 infection. Secondary isolated pericardial effusion and atypical neurological involvement are uncommon in Shiga-like toxin-producing Escherichia coli hemolytic uremic syndrome and should lead the physician to perform additional investigations.

Human Herpesvirus 6 Encephalitis in Immunocompetent and Immunocompromised Hosts.

ObjectiveThe aim of this study was to analyze the clinical, radiologic, and biological features associated with human herpesvirus 6 (HHV-6) encephalitis in immunocompetent and immunocompromised hosts to establish which clinical settings should prompt HHV-6 testing.MethodsWe performed a retrospective research in the virology database of Fondazione IRCCS Policlinico San Matteo (Pavia, Italy) for all patients who tested positive for HHV-6 DNA in the CSF and/or in blood from January 2008 to September 2018 and separately assessed the number of patients meeting the criteria for HHV-6 encephalitis in the group of immunocompetent and immunocompromised hosts.ResultsOf the 926 patients tested for HHV-6 during the period of interest, 45 met the study criteria. Among immunocompetent hosts (n = 17), HHV-6 encephalitis was diagnosed to 4 infants or children presenting with seizures or mild encephalopathy during primary HHV-6 infection (CSF/blood replication ratio <<1 in all cases). Among immunocompromised hosts (n = 28), HHV-6 encephalitis was diagnosed to 7 adolescents/adults with hematologic conditions presenting with altered mental status (7/7), seizures (3/7), vigilance impairment (3/7), behavioral changes (2/7), hyponatremia (2/7), and anterograde amnesia (1/7). Initial brain MRI was altered only in 2 patients, but 6 of the 7 had a CSF/blood replication ratio >1.ConclusionsThe detection of a CSF/blood replication ratio >1 represented a specific feature of immunocompromised patients with HHV-6 encephalitis and could be of special help to establish a diagnosis of HHV-6 encephalitis in hematopoietic stem cell transplant recipients lacking radiologic evidence of limbic involvement.

Effect of innate and adaptive immune mechanisms on treatment regimens in an AIDS-related Kaposi's Sarcoma model

Kaposi Sarcoma (KS) is the most common AIDS-defining cancer, even as HIV-positive people live longer. Like other herpesviruses, human herpesvirus-8 (HHV-8) establishes a lifelong infection of the host that in association with HIV infection may develop at any time during the illness. With the increasing global incidence of KS, there is an urgent need of designing optimal therapeutic strategies for HHV-8-related infections. Here we formulate two models with innate and adaptive immune mechanisms, relevant for non-AIDS KS (NAKS) and AIDS-KS, where the initial condition of the second model is given by the equilibrium state of the first one. For the model with innate mechanism (MIM), we define an infectivity resistance threshold that will determine whether the primary HHV-8 infection of B-cells will progress to secondary infection of progenitor cells, a concept relevant for viral carriers in the asymptomatic phase. The optimal control strategy has been employed to obtain treatment efficacy in case of a combined antiretroviral therapy (cART). For the MIM we have shown that KS therapy alone is capable of reducing the HHV-8 load. In the model with adaptive mechanism (MAM), we show that if cART is administered at optimal levels, that is, 0.48 for protease inhibitors, 0.79 for reverse transcriptase inhibitors and 0.25 for KS therapy, both HIV-1 and HHV-8 can be reduced. The predictions of these mathematical models have the potential to offer more effective therapeutic interventions in the treatment of NAKS and AIDS-KS.

Clinical Significance of Cerebrospinal Fluid Herpesvirus 6 Positivity- A Case Series Study

Human herpesvirus 6 (HHV-6) is a common pathogen at childhood, remains in a latent form and can reactivate, causing encephalitis with the impairment of the immune system. The acute primary HHV-6 infection in adult immunocompetent hosts is being questioned. The cerebrospinal fluid (CSF) HHV-6 positivity can be detected in infection, in latency period, in asymptomatic reactivation or in viral chromosomic integration. To establish the clinical significance of CSF HHV-6 positivity, the authors reviewed the CSF HHV-6 positive cases in a tertiary hospital from 13 years. A total of 2111 tests were made with 0.9% of HHV-6 positivity. Only 2 cases were considered “likely” HHV-6 infected, reinforcing that most positive results do not indicate infection. Immune status and quantitative viral load studies on CSF and blood can be of great benefit, but clinical judgement is fundamental to determine the significance of HHV-6 positivity and need for treatment.

Hemophagocytic Lymphohistiocytosis Due to Primary HHV-8 Infection in a Liver Transplant Recipient.

Human herpesvirus-8 (HHV-8) remains best known as an oncogenic virus, but nonneoplastic disease manifestations, such as bone marrow failure or hemophagocytic lymphohistiocytosis (HLH) have gained greater recognition in recent years. In organ transplantation, HHV-8 infection commonly occurs with reactivation of latent virus among recipients from endemic regions of the world or due to transmission from the organ donor. We describe a case of HHV-8–associated HLH in a liver transplant recipient at increased risk for primary infection. Our case highlights the risk of non–donor-derived, posttransplant primary HHV-8 infection, and demonstrates that HLH can be a life-threatening complication of this infection.

Primary infection with human herpes virus type 6, post-pediatric liver transplantation-A pathogen to remember.

In recent years, liver transplantation (LT) has become a well-accepted therapeutic modality for children with end-stage liver disease, with transplantation surgery being performed at a younger age. Human herpes virus 6 (HHV-6) infection occurs in most children within the first 2years of life, therefore, data on primary HHV-6 infection in pediatric liver transplant recipients is scarce. To describe the course of primary HHV-6 infection after pediatric LT. Medical files, between the years 2015-2016, of post-LT pediatric patients with suspected primary HHV-6 infection were reviewed. Clinical and laboratory data for enrolled cases were evaluated. Primary infection was defined as DNAemia in children who were seronegative prior to transplantation or seroconversion from negative to positive IgG posttransplantation. Four cases of primary HHV-6 (type B) infection were identified among the 26 children who had undergone LT at our center during the study period. All patients were <1year old and presented with fever, hepatitis, and elevated inflammatory markers, most (75%) within a short-period posttransplantation. All were initially treated with empiric antibiotics for a suspected bacterial infection and three underwent liver biopsy, one showing signs of rejection. Three were treated with antiviral therapy with a gradual resolution of symptoms. Primary HHV-6 should be taken into account in young children shortly after LT, especially when presenting with fever and elevated liver enzymes. Treatment with antiviral therapy should be considered. In young infants post-LT, a high index of suspicion may promote early detection of HHV-6 primary infection and prevent serious complications.

Acute liver dysfunction not resulting from hepatitis virus in immunocompetent children.

The aim of the present study was to clarify the roles of cytomegalovirus (CMV), Epstein-Barr virus (EBV), and human herpesvirus 6 (HHV-6) in immunocompetent children with acute liver dysfunction not resulting from hepatitis virus. Sixty-eight children (median age, 3 years) hospitalized as a result of acute liver dysfunction were enrolled in this study. Hepatitis A, B, and C were excluded. The prevalence of CMV, EBV, and HHV-6 and viral DNA load in whole blood was prospectively evaluated on multiplex real-time polymerase chain reaction (PCR). Of the 68 children with acute liver dysfunction, multiplex real-time PCR was positive in 30 (44%). CMV, EBV, and HHV-6 DNA were detected in 13 (19%), 14 (21%), and seven (10%), respectively. Serum CMV immunoglobulin (Ig)G/IgM and EBV viral capsid antigen IgG/IgM were measured in 40 (CMV DNA positive, n = 10; negative, n = 30) and 45 (EBV DNA positive, n = 14; negative, n = 31) of the 68 children, respectively. Eighteen percent (CMV, 7/40) and 9% (EBV, 4/45) were positive for both PCR and viral-specific IgM. There was no significant difference in CMV and EBV viral load between IgM-positive and -negative children with viremia. CMV, EBV, and HHV-6 DNA were frequently detected in immunocompetent children with acute liver dysfunction, but primary CMV and EBV infection were confirmed in 10-20% of the children with acute liver dysfunction. The combination of PCR assay and serology is necessary to make a diagnosis of acute liver dysfunction due to primary CMV, EBV and/or HHV-6 infection in immunocompetent children.

Human herpes virus 6 infection in pediatric organ transplant patients.

Transplant patients need lifelong immunosuppressive medication, but this reduces their defense mechanisms, making them prone to viral infections and reactivations. We aimed to clarify the prevalence and clinical manifestations of the human herpes virus 6 (HHV-6) infection in children after pediatric solid organ transplants. Clinical findings and viral loads were compared between primary HHV-6 infections and reactivations. The study comprised 47 kidney, 25 liver, and 12 heart transplant patients who underwent surgery from 2009 to 2014. HHV-6 antibodies were analyzed before surgery, and HHV-6 DNAemia tests were regularly carried out after the transplant using a real-time quantitative polymerase chain reaction method. We found the primary HHV-6 infection in 19 of 22 (86%) seronegative patients, and it was more common in patients under 3years of age (79%) than over 3 (38%, P=.0002). Post-transplant HHV-6 DNAemia affected 48 of 84 (57%) patients and was significantly higher in primary infections than reactivations (P=.001), and 17 of 48 (35%) patients had symptoms when it was detected at a median of 2weeks post-transplant. The HHV-6 infection was common after solid organ transplants, especially under 3years of age, and it typically started 2weeks after surgery. Testing for HHV-6 DNAemia is recommended shortly after transplantation, especially in patients with fever, diarrhea, rash, seizures, or abnormal liver enzyme tests.

Human Herpesvirus 6B Downregulates Expression of Activating Ligands during Lytic Infection To Escape Elimination by Natural Killer Cells.

Human herpesvirus 6 (HHV-6) latently infects a large portion of the human population and can reactivate in humans lacking a functional immune system, such as cancer or AIDS patients. Under these conditions, it can cause life-threatening diseases. To date, the actions and interplay of immune cells, and particularly cells of the innate immune system, during HHV-6 infection are poorly defined. In this study, we aimed to understand how cells undergoing lytic HHV-6 infection interact with natural killer (NK) cells, innate lymphocytes constituting the first line of defense against viral intruders. We show that HHV-6 suppresses the expression of surface proteins that alert the immune cells by triggering two major receptors on NK cells, NKG2D and NKp30. As a consequence, HHV-6 can replicate undetected by the innate immune system and potentially spread infection throughout the body. This study advances the understanding of HHV-6 biology and the measures it uses to successfully escape immune elimination.

Delayed primary HHV-7 infection and neurologic disease.

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. 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. Where sera were available, HHV-7 IgG antibody titers and avidity were measured to differentiate primary from past infection. HHV-7 DNA was detected in the CSF of 57 (1.9%) of the 2972 children tested. In 3 adolescents primary HHV-7 infection (low avidity IgG) was confirmed as the cause of neurologic disease, 2 who had encephalitis and 1 who had Guillain-Barré syndrome. Eighteen children had possible HHV-7 disease (no alternative cause identified and indeterminate antibody result or serum not available), 7 encephalitis, 8 meningitis, and 3 demyelinating disorders. HHV-7 disease was excluded in 36 children on the basis of past infection (high IgG avidity) and/or an alternative cause. Primary HHV-7 infection delayed into adolescence can cause serious neurologic disease. HHV-7 DNA in CSF alone is insufficient to prove an etiologic association. Combining CSF polymerase chain reaction with serology is essential to prove primary infection when investigating HHV-7 CNS disease.

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Human Herpesvirus 6, 7 and 8 in Solid Organ Transplantation

Primary and Reactivated HHV8 Infection and Disease After Liver Transplantation: A Prospective Study

Human herpesvirus 8 (HHV8) is pathogenic in humans, especially in cases of immunosuppression. We evaluated the risk of HHV8 transmission from liver donors, and its clinical impact in southern Italy, where its seroprevalence in the general population is reported to be as high as 18.3%. We tested 179 liver transplant recipients and their donors for HHV8 antibodies at the time of transplantation, and implemented in all recipients a 12-month posttransplant surveillance program for HHV8 infection. Of the 179 liver transplant recipients enrolled, 10.6% were HHV8 seropositive before transplantation, whereas the organ donor's seroprevalence was 4.4%. Eight seronegative patients received a liver from a seropositive donor, and four of them developed primary HHV8 infection. Two of these patients had lethal nonmalignant illness with systemic involvement and multiorgan failure. Among the 19 HHV8 seropositive recipients, two had viral reactivation after liver transplantation. In addition, an HHV8 seronegative recipient of a seronegative donor developed primary HHV8 infection and multicentric Castleman's disease. In conclusion, primary HHV8 infection transmitted from a seropositive donor to a seronegative liver transplant recipient can cause a severe nonmalignant illness associated with high mortality. Donor screening for HHV8 should be considered in geographic areas with a high prevalence of such infection.

Human Herpes Virus 8 in Solid Organ Transplantation

Human herpes virus 8 (HHV-8) is a geographically limited virus that causes neoplastic and nonneoplastic diseases predominantly in endemic regions. Primary HHV-8 infection, which is usually asymptomatic in immunocompetent individuals, result in lifelong latency. When the equilibrium between virus and host immunity is disturbed, such as after organ transplantation, HHV-8 may activate molecular pathways that drive oncogenesis. Kaposi's sarcoma, primary effusion lymphoma, and Castleman's disease are the major malignancies associated with HHV-8. The incidences of these neoplastic pathologies mirror the geographic HHV-8 seroprevalence, and certain groups of patients are at higher risk. In this context, the risk of HHV-8 and its clinical disease is highest in immunocompromised patients, including transplant recipients. Solid organ transplant recipients from HHV-8 endemic regions may develop HHV-8 reactivation or primary infection and manifest with Kaposi's sarcoma or less commonly primary effusion lymphoma and Castleman's disease; these neoplastic diseases are reported much less commonly in low-prevalent areas. There is currently no standard method of screening for HHV-8 infection in the transplant setting, although HHV-8 polymerase chain reaction is available to confirm clinical suspicion of infection. Management of HHV-8-associated diseases entails primarily a reduction in the degree of pharmacologic immunosuppression and, in some cases, chemotherapy may be required. The mammalian target of rapamycin inhibitor sirolimus may have the potential for management because of its antiproliferative properties. The role of antiviral drugs for HHV-8 prevention and treatment is yet to be defined.

Detection of human herpesvirus 7 infection in young children presenting with exanthema subitum

In this study, we assessed the prevalence of human herpesvirus-7 (HHV-7) in 141 serum samples from children less than four years of age with exanthematic disease. All samples were negative for measles, rubella, dengue fever and parvovirus B19 infection. Testing for the presence of human herpesvirus-6 (HHV-6)-specific high avidity IgG antibodies by indirect immunofluorescence assay (IFA) revealed two main groups: one composed of 57 patients with recent primary HHV-6 infection and another group of 68 patients showing signs of past HHV-6 infection. Another 16 samples had indeterminate primary HHV-6 infection, by both IgG IFA and IgM IFA. Serum samples were subjected to a nested polymerase chain reaction to detect the presence of HHV-7 DNA. Among patients with a recent primary HHV-6 infection, HHV-7 DNA was present in 1.7% of individuals; however, 5.8% of individuals tested positive for HHV-7 DNA in the group with past primary HHV-6 infection. Among the 16 samples with indeterminate diagnosis, 25% (4/16) had HHV-7 DNA (p < 0.002). We hypothesise that HHV-7 might be the agent that causes exanthema. However, a relationship between clinical manifestations and the detection of virus DNA does not always exist. Therefore, a careful interpretation is necessary to diagnose a primary infection or a virus-associated disease. In conclusion, we detected HHV-7 DNA in young children from the state of Rio de Janeiro, Brazil.

Kinetics of cytokine and chemokine responses in patients with primary human herpesvirus 6 infection

Background Cytokines and chemokines induced by human herpesvirus 6 (HHV-6) infection may play an important role in the observed HHV-6-associated clinical complications. However, basic data for cytokine and chemokine synthesis in primary HHV-6 infected patient without complication is lacking. Objective Aim of this study was to elucidate basic kinetic data for expressions of cytokines and chemokines in patients with primary HHV-6 infection without complication. Study design Twenty-six patients suffering from fever were enrolled in this study. Fourteen biomarkers were measured in 74 serially collected sera samples from 26 patients. Additionally, serum samples obtained from 14 healthy children were used for control. Results Twenty of the 26 patients were diagnosed with primary HHV-6 infection based on viral isolation and serological analysis. The mean age ( P = 0.1289) and proportion of males to females ( P = 0.9999) between the patients with and without primary HHV-6 infection were not statistically different. At the acute phase of the disease, three cytokines (IFN-γ; P = 0.0046, IL-2; P = 0.0366, and IL-4; P = 0.0255) and one chemokine (MCP-1; P = 0.0019) were significantly higher in patients with primary HHV-6 infection compared to those without infection. Interleukin-5 levels during the convalescent period were significantly higher in patients with HHV-6 infection ( P = 0.0205). By 1 month post-infection, cytokine and chemokine expression had returned to almost basal levels. Conclusion As suggested by the previous in vitro studies, present in vivo analysis also suggests that HHV-6 has potency for induction of cytokines and chemokines.

Human Herpesvirus-6 Entry into Host Cells

Human herpesvirus-6 (HHV-6) belongs to the herpesvirus family and is categorized into variant A and B (HHV-6A and HHV-6B). Primary HHV-6 infection in children and its related diseases are almost exclusively caused by HHV-6B and no disease caused by HHV-6A has been identified. The cellular receptor of HHV-6 has been shown to be a human CD46, and its viral ligand is an envelope glycoprotein complex, gH/gL/gQ1/gQ2 in HHV-6A. Furthermore, both cellular and viral lipid rafts play an important role in the HHV-6 entry process, suggesting that HHV-6 may enter its target cells through a lipid raft-associated mechanism.

Human herpesvirus‐6 in patients with Crohn’s disease

Human herpesvirus-6 (HHV-6) infections are usually asymptomatic reactivations in immunocompetent persons, but may be severe in immunocompromised individuals. Although primary HHV-6 infection is mainly associated with roseola infantum, it has also been associated with gastroenteritis, diarrhea, and nausea in children. In this study, we investigated the potential role of HHV-6 in Crohn's disease (CD). Evidence of HHV-6 infection in CD patients and controls was determined by immunohistochemistry (IHC), polymerase chain reaction (PCR), and quantitative real-time PCR (qPCR). Fifty-one tissue blocks from 23 CD patients and 20 tissue blocks from 20 controls were examined. Quantitativereal-time PCR was used to assess HHV-6 viral loads. IHC, PCR and qPCR indicated the presence of HHV-6 in both CD patients and controls. Immunohistochemistry of tissues revealed an almost equal frequency and distribution of positive cells; however, non-specific immunostaining confounded interpretation. HHV-6 DNA was detected in 52% (12/23) of CD and 55% (11/20) of control patients by PCR and in 69.5% (16/23) of CD cases and 65% (13/20) of controls by qPCR. Mean viral load in intestinal tissues was similar in CD and controls (33.4 and 57.9 copies microg(-1) DNA, respectively). Finding equal evidence of HHV-6 in patients and controls by multiple methods suggests that this virus is ubiquitous and probably not a cause of CD.

Diagnostic assays for active infection with human herpesvirus 6 (HHV-6)

Background Human herpesvirus 6 (HHV-6) causes ubiquitous infection in early childhood with lifelong latency or persistence. Reactivation of HHV-6 has been associated with multiple diseases including encephalitis. Chromosomal integration of HHV-6 also occurs. Previous studies have suggested that the detection of HHV-6 DNA in plasma is an accurate marker of active viral replication. Objective We sought to determine whether PCR assays on plasma could correctly differentiate between primary HHV-6 infection, chromosomal integration of HHV-6 and latent HHV-6 infection. Study design We performed qualitative PCR, real-time quantitative PCR (RQ-PCR), and reverse-transcriptase PCR (RT-PCR) assays on samples of peripheral and cord blood mononuclear cells, as well as plasma, from groups of subjects with well defined HHV-6 infection, including subjects with chromosomally integrated HHV-6. Results and conclusions The detection of HHV-6 DNA in plasma was 92% sensitive compared to viral isolation for the identification of primary infection with HHV-6. All plasma samples from infants with chromosomally integrated HHV-6 had HHV-6 DNA detectable in plasma while only 5.6% were positive by RT-PCR. The specificity of plasma PCR for active replication of HHV-6 was 84% compared to viral culture while the specificity of RT-PCR was 98%. Our results demonstrate that qualitative or quantitative PCR of plasma is insufficient to distinguish between active viral replication and chromosomal integration with HHV-6. We found a higher specificity of RT-PCR performed on PBMC samples compared to PCR or RQ-PCR performed on plasma when evaluating samples for active HHV-6 replication.

Impact of human herpes virus 6 in liver transplantation

Human herpes virus 6 (HHV-6) infects > 95% of humans. Primary infection which occurs mostly during the first 2 years of life in the form of roseola infantum, non-specific febrile illness, or an asymptomatic illness, results in latency. Reactivation of latent HHV-6 is common after liver transplantation. Since the majority of human beings harbor the latent virus, HHV-6 infections after liver transplantation are most probably caused by endogenous reactivation or superinfection. In a minority of cases, primary HHV-6 infection may occur when an HHV-6-seronegative individual receives a liver allograft from an HHV-6-seropositive donor. The vast majority of HHV-6 infections after liver transplantation are asymptomatic. Only in a minority of cases, when HHV-6 causes a febrile illness associated with rash and myelosuppression, hepatitis, gastroenteritis, pneumonitis, and encephalitis after liver transplantation. In addition, HHV-6 has been implicated in a variety of indirect effects, such as allograft rejection and increased predisposition to and severity of other infections, including cytomegalovirus, hepatitis C virus, and opportunistic fungi. Because of the uncommon nature of the clinical illnesses directly attributed to HHV-6, there is currently no recommended HHV-6-specific approach prevention after liver transplantation. Asymptomatic HHV-6 infection does not require antiviral treatment, while treatment of established HHV-6 disease is treated with intravenous ganciclovir, foscarnet, or cidofovir and this should be complemented by a reduction in immunosuppression.