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A unique presentation of acute liver failure from herpes simplex virus hepatitis.

We present the case of a patient, with history of myelodysplastic syndrome and recent bone marrow transplant, who developed fulminant liver failure secondary to herpes simplex virus (HSV) hepatitis. His presentation was unique, as findings of liver microabscesses on computed tomography scan have not been described previously in this patient population. Despite initial treatment with acyclovir, he continued to deteriorate, and later sensitivities found the HSV strain to be resistant to acyclovir. HSV hepatitis with secondary liver failure is rare and, without appropriate treatment, its mortalit

Clinical and immunological considerations in Epstein-Barr virus-associated diseases.

Despite the fact that nucleoside analogues, such as aciclovir and ganciclovir, and DNA-polymerase inhibitors, such as foscarnet, have a proven antiviral effect on oropharyngeal-Epstein-Barr virus (EBV) replication, they have been unable to show any effect on the severity or duration of infectious mononucleosis (IM), a condition for which there is currently no established treatment. Clinical symptoms may be due to an EBV-induced polyclonal humoral, as well as cellular, immunoreactivity with limited pathology caused by viral replication itself. However, despite an extensive immune response, 90% …

Time to initiation of pre-emptive therapy for cytomegalovirus impacts overall survival in pediatric hematopoietic stem cell transplant recipients.

BACKGROUND AIMS: Cytomegalovirus (CMV) reactivation is a significant complication following allogeneic hematopoietic stem cell transplant (H … . For those patients who reactivated CMV, 30 (81%) received induction treatment with ganciclovir or foscarnet. To analyze the impact of the timing of induction treatment on clinical outcomes, the authors restricted the analysis to those patients who reactivated CMV and received induction treatment (n = 30). The timing of induction treatment was significantl …

Antiviral drugs for viruses other than human immunodeficiency virus.

Most viral diseases, with the exception of those caused by human immunodeficiency virus, are self-limited illnesses that do not require specific antiviral therapy. The currently available antiviral drugs target 3 main groups of viruses: herpes, hepatitis, and influenza viruses. With the exception of the antisense molecule fomivirsen, all antiherpes drugs inhibit viral replication by serving as competitive substrates for viral DNA polymerase. Drugs for the treatment of influenza inhibit the ion channel M(2) protein or the enzyme neuraminidase. Combination therapy with Interferon-α and ribavirin

CMV complications in common variable immunodeficiency.

A patient suffering from common variable immunodeficiency is described, who developed a myelitis under treatment with glucocorticosteroids. Later on, autoimmune complications had to be treated with azathioprine. An exacerbation of the myelitis, retinitis, encephalitis and colitis was observed and a cytomegalovirus infection diagnosed. This infection does not represent a typical complication of common variable immunodeficiency. A functional NK cell defect was detected that may contribute to susceptibility for cytomegalovirus infection in addition to immunosuppressive therapy.

Case Report: Varicella-zoster Encephalitis with Acute Retinal Necrosis and Oculomotor Nerve Palsy.

SIGNIFICANCE: Varicella-zoster virus is a common cause of morbidity and vision loss in patients worldwide. It can affect any structure of the eye, from keratitis to acute retinal necrosis. Rapid diagnosis and treatment significantly improve clinical outcomes and quality of life. PURPOSE: The purpose of this study was to demonstrate a case where urgent referral to the emergency department was required to treat a patient with disseminated herpes zoster infection. CASE REPORT: This is a rare case of varicella-zoster virus encephalitis in a 70-year-old immunocompetent white man who initially pre

Role of the sodium-dependent phosphate co-transporters and of the phosphate complexes of uranyl in the cytotoxicity of uranium in LLC-PK1 cells.

Although uranium is a well-characterized nephrotoxic agent, very little is known at the cellular and molecular level about the mechanisms underlying the uptake and toxicity of this element in proximal tubule cells. The aim of this study was thus to characterize the species of uranium that are responsible for its cytotoxicity and define the mechanism which is involved in the uptake of the cytotoxic fraction of uranium using two cell lines derived from kidney proximal (LLC-PK(1)) and distal (MDCK) tubule as in vitro models. Treatment of LLC-PK(1) cells with colchicine, cytochalasin D, concanaval

Management of human cytomegalovirus infection and disease after allogeneic bone marrow transplantation.

BACKGROUND AND OBJECTIVE: Human cytomegalovirus (HCMV) infection and disease remain a major cause of morbidity and mortality after bone marrow transplantation. HCMV disease, especially pneumonitis, may be treated with ganciclovir and immunoglobulin but even so the outcome is poor with mortality rates of 30-70%. It is therefore imperative to treat HCMV infection before it develops into disease. The aim of this article is to describe the main strategies used to prevent HCMV infection and to improve the survival after CMV disease in bone marrow transplant recipients. INFORMATION SOURCES: In the

Human herpesvirus 6.

HHV-6, the first T-lymphotropic human herpesvirus, is an important novel human pathogen. It is the cause of exanthem subitum in infants and may act as an opportunistic agent in immunocompromised patients. Moreover, several lines of clinical and experimental evidence suggest that HHV-6 may accelerate the progression of HIV infection. Progress in the study of HHV-6 has been rapid, in part as a consequence of the strong current interest in human lymphotropic viruses and their relationship with the immune system. Nonetheless, the full spectrum of diseases linked to this agent is still unknown (Tab

Impact of Primary Letermovir Prophylaxis Versus Preemptive Antiviral Therapy for Cytomegalovirus on Economic and Clinical Outcomes after Hematopoietic Cell Transplantation.

Preemptive therapy (PET) historically has been the primary strategy to reduce early-onset cytomegalovirus (CMV) reactivation after allogenei … .001) patients who were given LTV prophylaxis with corresponding reductions in val(ganciclovir) and foscarnet (HR CMV only) use. Among HR CMV patients, LTV prophylaxis was associated with reductions in CMV-related readmissions (3/54, 5.6% versus 18/54, 33.3%, P < .001) and outpatient visits within the first 100 days after HCT (20 versus 25, P = .002), and a …

Utility of ultra-deep sequencing for detection of varicella-zoster virus antiviral resistance mutations.

We report the first application of ultra-deep sequencing (UDS) to varicella-zoster virus (VZV) genotypic antiviral testing in a case of acyc … yclovir (ACV) and its prodrug valacyclovir (VACV) are considered as the first-line therapy, whereas foscarnet (FOS) or cidofovir (CDV) constitute alternative options. After primophosphorylation by the viral thymidine kinase (TK), ACV targets the viral DNA polymerase and inhibits the viral genome replication by a chain termination mechanism. According to thi …

Early appearance of simian immunodeficiency virus (SIV) antigen and antibodies as variables in evaluating antiviral drugs in macaques.

SIV infection in macaques has become an important animal model for HIV-1 infection in humans. An antibody assay was therefore developed and compared to a commercially available antigen assay with respect to their usefulness to monitor the course of simian immunodeficiency virus (SIV) infection in cynomolgus monkeys. A peptide, JB6T, consisting of 21 amino acids with the sequence NSWGCAFRQVCHTTVPWVNDS corresponding to a segment in the env protein of human immunodeficiency virus (HIV) type 2 was used as antigen in an enzyme-linked immunosorbent assay (ELISA). JB6T was found to detect IgG and IgM

Brincidofovir clearance of acyclovir-resistant herpes simplex virus-1 and adenovirus infection after stem cell transplantation.

Infections with adenovirus (AdV) and herpesviruses can result in considerable morbidity and mortality in pediatric hematopoietic stem cell transplant (SCT) recipients. Herpes simplex virus (HSV) reactivations are usually prevented by acyclovir (ACV) prophylaxis, whereas cidofovir (CDV) has been used off indication to manage AdV infections. We report a child with myelodysplastic syndrome undergoing multiple SCT, who experienced HSV-1 disease including severe mucositis and herpetic whitlow, as well as high viral load AdV DNAemia. Both ACV and CDV were ineffective; however, viral loads were decre

Clinical and healthcare burden of disease associated with cytomegalovirus in allogeneic hematopoietic stem cell transplantation - A retrospective single-center study.

BACKGROUND: CMV infection is a common complication in allogeneic hematopoietic stem cell transplantation (HSCT). We investigated the association of clinically significant CMV (CS-CMV) infection with clinical outcomes and healthcare resource utilization in allogeneic HSCT patients in Finland. METHODS: This retrospective study included adult patients who received their first allogeneic HSCT between January 1, 2013, and December 31, 2018, at the Turku University Hospital. Data were collected from the hospital data lake. Clinical and healthcare outcomes were investigated at one year and mortality

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… In patients with CS‐CMV infection, 73.0% and 62.2% received valganciclovir and foscarnet, respectively. Ganciclovir (36.5%) was less often used. … Patients with grade 3–4 acute GVHD received more often foscarnet (51.0% vs. 33.2%, p = .020), and the total dose of foscarnet was higher compared to the patients with grade ≤2 acute GVHD (Table S3 ). …

Advances in CMV Management: A Single Center Real-Life Experience.

CMV infection is a major challenge in allogeneic stem cell transplantation (allo-SCT). The changing landscape in CMV management includes the introduction of letermovir in prophylaxis of high-risk patients and the source of CMV DNA monitoring (plasma-PL vs. whole blood-WB), for pre-emptive therapy (PET) initiation. We report here how our real-life experience in CMV management evolved, following letermovir registration. We focus on: (i) the effects of systematic use of letermovir for CMV prophylaxis in high-risk patients, (ii) the results of a longitudinal comparison of CMV DNAemia monitoring in

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… Letermovir discontinuation at day + 40 because of foscarnet therapy for HHV6 reactivation. … No resistance to ganciclovir or foscarnet was observed. …

Acute Retinal Necrosis: Virological Features Using Quantitative Polymerase Chain Reaction, Therapeutic Management, and Clinical Outcomes.

PURPOSE: To evaluate outcomes of patients treated with intensive intravitreal therapy and to describe the evolution of quantitative real-time polymerase chain reaction (qPCR) in patients treated for acute retinal necrosis (ARN) syndrome. DESIGN: Retrospective observational case series. METHODS: This study included 25 eyes of 24 patients with ARN who were treated and followed up in 2 departments of ophthalmology in Lyon, France. Assessed outcomes included qPCR viral load profile during treatment, number of antiviral intravitreal injections (IVT), retinal detachment rate, and best-corrected vi

Varicella-Zoster Virus Infection and Varicella-Zoster Virus Vaccine-Related Ocular Complications.

The varicella-zoster virus is a human herpesvirus that causes varicella as the primary infection and HZ as the reactivation of a latent infection. Ten to twenty percent of cases of herpes zoster ophthalmicus (HZO) involve the ophthalmic branch of the fifth cranial nerve. Any area of the eye may be affected by the condition. HZ has a lifetime risk of more than 30%. Complications from herpes zoster can significantly lower quality of life. The goal of HZ vaccinations is to stop HZ activation and PHN formation. Despite the uncommon possibility of side effects such as eye problems, the majority of

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… corneal endothelium and punctate epithelial erosions Ali et al. [ 57 ] | ARN and contralateral cutaneous eruption | ZOSTAVAX | Live attenuated | 63 | M | varicella skin eruption on the right side of his face | insidious deterioration in vision | VZV DNA (+) | none | 3 months after vaccination | io foscarnet … of active retinitis Menghini et al. [ 62 ] | ARN with obliterative angiopathy (left eye) | ZOSTAVAX | Live attenuated | 76 | M | none | blurry vision, slight pain, and redness | wild-type VZV DNA (+) | insulin-dependent diabetes mellitus, chronic lymphocytic leukemia | 2 days after vaccination | io foscarnet …

Infections in Recipients of Hematopoietic Stem Cell Transplants

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… Foscarnet and cidofovir are acceptable alternatives. Renal dose adjustment is required for all antiviral agents. ‡ Foscarnet, high-dose acyclovir, or valacyclovir are acceptable alternatives. Renal dose adjustment required for all antiviral agents. … Foscarnet is administered in doses of 90 mg/kg intravenously every 12 hours for induction and 90 mg/kg intravenously every 24 hours for maintenance. Good urine flow can minimize irritation of the urethra and labia by foscarnet. …

Preventing Varicella-Zoster: Advances With the Recombinant Zoster Vaccine.

Prevention strategies against varicella zoster infection include chemoprophylaxis with acyclovir and live attenuated zoster vaccine. However, resistance to acyclovir has been problematic, and safety concerns have limited the use of the live attenuated vaccine in immunosuppressed patients. Recombinant zoster vaccine, made available in 2017 for the immunocompetent host, has been evaluated for safety, immunogenicity, and efficacy in several immunocompromised settings as well. The present review compares the live attenuated vaccine and the recombinant zoster vaccine and highlights data on the use

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… Alternative drugs to treat resistant cases are foscarnet and cidofovir. Use of foscarnet and cidofovir is limited, as they are only available as intravenous formulations and have a narrow therapeutic index. … Foscarnet nephrotoxicity: mechanism, incidence and prevention. Am J Nephrol 1989; 9:316–21. 22. Poole CL, James SH. Antiviral therapies for herpesviruses: current agents and new directions. Clin Ther 2018; 40:1282–98. 23. Chono K, Katsumata K, Kontani T, et al. …

Long term renal survival in patients undergoing T-Cell depleted versus conventional hematopoietic stem cell transplants.

Calcineurin inhibitor (CNI)-sparing T-cell depleted (TCD) hematopoietic stem cell transplants (HSCTs) are presumed to be less nephrotoxic than conventional HSCTs. We evaluated incidence and risk factors for kidney failure and chronic kidney disease (CKD) in 231 TCD and 212 conventional HSCT recipients. Kidney failure required a median glomerular filtration rate (GFR) 2 for ⩾100 days anytime after 180-days post-HSCT. Two-year cumulative incidence (CI) of kidney failure was 42% in the conventional versus 31% in the TCD group (P=0.005). TCD, age, acute kidney injury and number of toxic CNI levels

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… During the peri-transplant period patients received several potentially nephrotoxic medications including cidofovir, amikacin, liposomal amphotericin and foscarnet. … Toxic exposure was defined as >1 day administration of cidofovir and >5 days of amikacin, liposomal amphotericin or foscarnet ( 25 – 28 ). Biostatistics Descriptive statistics were used to summarize patient and treatment characteristics by transplant type (conventional and TCD). …