Human Herpesvirus-6 Infection In Patients Research Articles

Guidelines from the 2017 European Conference on Infections in Leukaemia for management of HHV-6 infection in patients with hematologic malignancies and after hematopoietic stem cell transplantation.

Of the two human herpesvirus 6 (HHV-6) species, human herpesvirus 6B (HHV-6B) encephalitis is an important cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant. Guidelines for the management of HHV-6 infections in patients with hematologic malignancies or post-transplant were prepared a decade ago but there have been no other guidelines since then despite significant advances in the understanding of HHV-6 encephalitis, its therapy, and other aspects of HHV-6 disease in this patient population. Revised guidelines prepared at the 2017 European Conference on Infections in Leukaemia covering diagnosis, preventative strategies and management of HHV-6 disease are now presented.

Cytokine and cellular responses to human herpesvirus-6B in patients with B-acute lymphoblastic leukemia.

Primary infection with human herpesvirus-6 (HHV-6), is followed by its lifelong persistence in the host. Most T-cell responses to HHV-6 have been characterized using peripheral blood from healthy adults; however, the role of HHV-6 infection in immune modulation has not been elucidated for some diseases. Therefore, in this study the immune response to HHV-6 infection in patients with B-acute lymphoblastic leukemia (B-ALL) was analyzed. HHV-6 load was quantified in blood samples taken at the time of diagnosis of leukemia and on remission. The same concentrations of anti- and pro-inflammatory cytokines (IL-4, IL-1, IL-6, IL-8, IL-12p70, IL-17a, TNF-α and IFN-γ) were detected in plasma samples from 20 patients with and 20 without detectable HHV-6 virus loads in blood. Characterization of T-cell responses to HHV-6 showed low specific T-cells frequencies of 2.08% and 1.46% in patients with and without detectable viral loads, respectively. IFN-γ-producing T cells were detected in 0.03%-0.23% and in 0%-0.2% of CD4+T cells, respectively. Strong production of IL-6 was detected in medium supernatants of challenged T-cells whatever the HHV-6 status of the patients (973.51 ± 210.06 versus 825.70 ± 210.81 pg/mL). However, concentrations of TNF-α and IFN-γ were low. Thus, no association between plasma concentrations of cytokines and detection of HHV-6 in blood was identified, suggesting that HHV-6 is not strongly associated with development of B-ALL. The low viral loads detected may correspond with latently infected cells. Alternatively, HHV-6B specific immune responses may be below the detection threshold of the assays used.

High seroprevalence of human herpesvirus 8 infection in patients with systemic lupus erythematosus

Systemic lupus erythematosus (SLE) is an autoimmune disease that is associated with genetic and environmental factors and microbial infection. With respect to microbial infection, the Epstein-Barr virus (EBV) has been a widely discussed issue in recent decades. Human herpesvirus 8 (HHV-8) belongs to the same γ-herpesvirus subfamily as EBV and is closely related to it. Until now, only one paper has reported the prevalence of HHV-8 infection in SLE patients. The goal of this study was to detect the prevalence of HHV-8 infection in SLE patients to elucidate the relationship between HHV-8 and SLE. We assessed the seroprevalence of HHV-8 in SLE patients by immunofluorescence assay. In addition, we quantified the HHV-8 DNA in peripheral blood mononuclear cells (PBMCs) from SLE patients by real-time polymerase chain reaction (PCR). The prevalence of HHV-8 antibodies in SLE and normal controls was 57.8% (26/45) and 19.2% (5/26), respectively. These data were highly significant (P = 0.001). No HHV-8 DNA was detected by real-time PCR in SLE patients' PBMCs. In addition, we analyzed the prevalence of HHV-8 infection in patients with rheumatoid arthritis and ankylosing spondylitis. There was no significant difference between the patients and normal controls. A high seroprevalence of HHV-8 infection was found in patients with SLE. The negative DNA load and high seropositive rate indicate that most patients might have latent infection.

Prevalence of human herpesvirus 8 infection in Iranian patients with hematological malignancies

Human herpesvirus 8 (HHV-8) is a gamma-herpesvirus linked causally to Kaposi’s sarcoma and many malignancies such as multicentric Castleman’s disease, primary effusion lymphoma, some lymphoproliferative diseases and post transplantation bone marrow failure. The aim of this study was to determine the prevalence of HHV-8 infection in patients with malignant hematological diseases. From September, 2009 to April, 2010, 62 patients with hematological diseases were recruited for the study. Five milliliter of ethylenediaminetetraacetic acid (EDTA) anti-coagulated peripheral blood was collected from each subject. The presence of HHV-8 DNA was tested using a real time technology for the sequences from HHV-8 ORF65. The mean age of patients was 33.9 ± 18.0 years. Four of the patients were found to be HHV-8 polymerase chain reaction (PCR) positive using Real time-PCR and viral prevalence was 6.5%. HHV-8 was found in 1 (25%) patient with acute myelogenous leukemia (AML), 3 (75%) patients with chronic myelogenous leukemia (CML), and none was detected in patients with acute lymphoblastic leukemia (ALL) and lymphoma. The results of this study show that patients with malignant hematological diseases may have HHV-8 infection, therefore, it seems that considering HHV-8 infection in patients with hematological malignancies might be beneficial. Key words: Human herpesvirus 8 (HHV-8), malignant hematological diseases, prevalence, Iran.

Serum-Negative, Site Specific HHV-6 Infection Causes Nausea and Vomiting Following Double Umbilical Cord Stem Cell Transplantation

Purpose: Current literature describes similar clinical manifestations between human herpes virus 6 (HHV-6) infection and graft versus host disease (GvHD) in post-hematopoietic stem cell transplant (HSCT) recipients. Therefore, it is essential to consider HHV-6 infection in patients with gastrointestinal (GI) symptoms suggestive of GvHD. We present a case that highlights the importance of testing gastroduodenal tissue as an adjunct to serological testing of HHV-6 in this patient population. A 30-year old woman (HHV-6 IgG +) with acute lymphocytic leukemia (ALL) presented for a double umbilical cord stem cell transplant with myeloablative conditioning. Her post-transplant course was complicated by late engraftment, Klebsiella pneumoniae sepsis, BK cystitis, HHV-6 viremia and biopsy-proven stage 4 GvHD of the upper and lower GI tract associated with fever, abdominal pain, diarrhea and vomiting. She was treated with 3 months of high dose steroids for GvHD and one month of a combination of IV foscarnet and oral valganciclovir for HHV-6 reactivation (viral load 66,292 cpy/ml). Her symptoms improved (viral load undectable), but she then returned to the hospital day + 150 post transplant for dehydration secondary to persistent nausea and vomiting. Serum PCR testing for HHV-6 and gastroduodenal biopsies for GvHD were negative. However, PCR of gastroduodenal tissue biopsies for HHV-6 was positive (viral load 5,912 viral copies/1,000 cell equivalent). She was restarted on valgancyclovir for 4 weeks and had total resolution of her symptoms at the end of this time. HHV-6 is a lymphotrophic virus which belongs to the β-herpesviridae family. It typically remains latent in certain host cells but can reactivate in immunocompromised patients. In HSCT recipients, gastrointestinal complications of HHV-6 may include abdominal pain, nausea, vomiting, diarrhea, cholestasis and hepatitis which mimics and can worsen the grade of GvHD. Cord blood transplant recipients and previous episodes of GvHD are found to be predictors of HHV-6 reactivation, as was seen in our patient. This case highlights that HHV-6 viremia need not be synchronous with a site-specific infection in HSCT patients with upper GI symptoms. Given the prevalence and correlation between GI manifestations of HHV-6 and GvHD, isolated local infection should be considered in the differential diagnosis of persistent GI symptoms despite serumnegative HHV-6 testing. The clinical benefit of treating biopsy-proven HHV-6 of the GI tract should be further studied in patients with and without GvHD post-HSCT.

Human herpesvirus 8 shedding in the mouth and blood of hemodialysis patients

In Saudi Arabia, the prevalence of transplantation-associated Kaposi's sarcoma (KS) is high, and there is disparity in the prevalence rates of human herpesvirus 8 (HHV-8) infection between patients with renal disease and the general population. It was hypothesized that oral HHV-8 transmission among patients undergoing hemodialysis treatment contributes to the high prevalence of infection in renal disease patients. The detection rates of anti-HHV8-IgG in plasma and HHV-8-DNA in CD45(+)-peripheral blood cells of 72 hemodialysis patients were compared first with those of 178 blood donors and 60 pregnant women. Between the hemodialysis patients and the apparently healthy people sampled, the detection rate of anti-HHV-8-IgG was 16.7% versus 0.4% (P < 0.001) and that of HHV-8-DNA was 4.2% versus 0.4%, (P < 0.05). HHV-8 DNA was determined in oral samples and the HHV-8 viral load measured in saliva of patients undergoing hemodialysis. The amount of virus shed into saliva ranged between 8,600 and 119,562,500 (mean: 24,009,360) genome-equivalents/ml among the five patients in whom oral HHV-8 DNA was detected. Finally, HHV-8-subgenomic sequencing was conducted which showed that orally shed HHV-8 in four patients belonged to genotype C2, and in one patient to genotypes A1 and C2. HHV-8 shed in the mouth of hemodialysis patients may be extensive and diverse. Oral fluid in addition to blood is thus a likely vehicle for transmission of HHV-8, possibly contributing to the high risk of HHV-8 infection in patients undergoing hemodialysis and to KS following immunosuppression after renal transplantation.

Human Herpesvirus 8 Infections and AIDS-Associated Kaposi Sarcoma in Zaria, Northern Nigeria

Studies on human herpesvirus 8 (HHV8) infection in patients with AIDS-associated Kaposi sarcoma (AIDS-KS), from Nigeria are lacking. We examined the seroprevalence of HHV8 infection in patients with AIDS-KS presenting to Ahmadu Bello University Teaching Hospital (ABUTH), Zaria, Nigeria, and also described their clinical presentation. A total of 20 (11 males and 9 females) histologically confirmed adults with AIDS-KS were recruited consecutively in 2007. The clinical types of lesions, associated diseases, and the AIDS clinical trial group staging of AIDS-KS were noted. Anti-lytic HHV8 antibodies were determined by enzyme-linked immunosorbent assay (ELISA). Kaposi sarcoma skin lesions were diverse but mostly nodules (19 cases) and papules (16). Majority (18 cases) had poor risk AIDS-KS, with 10 (50%) patients having concomitant opportunistic infections and 3 (15%) patients having generalized skin lesions. Females had a more severe disease. Seventeen patients (85%) were HHV8-seropositive. AIDS-KS is associated with high HHV8 infection and presents with a variety of skin manifestations that are often aggressive, advanced, and worse in females.

What's New in Human Herpesvirus-6?: Clinical Immunopathology of the HHV-6 Infection

Human herpesvirus-6 (HHV-6), formerly known as human B-lymphotropic virus (HBLV), was first isolated in 1986 from patients with lymphoproliferative disorders and AIDS. Antibody prevalence against HHV-6 varies between about 60-80% indicating a widespread latent infection. Although HHV-6 infects in vivo primarily T-lymphocytes, it is associated with similar diseases as in infection with Epstein-Barr virus (EBV), a clearly B-lymphotropic virus. Reactivation of latent HHV-6 infection in patients with subnormal host defense may cause persistent active infection with so-called postinfectious chronic fatigue syndrome (PICFS) or may contribute to other pathologies such as immune deficiency itself, autoimmune disorders or progressive lymphoproliferation. Coinfection of CD4 cells by HHV-6 and human immunodeficiency virus (HIV 1) in AIDS patients can aggravate HIV-induced acquired immune deficiency. These characteristics of the only recently detected new virus justify further intense investigation.