VZV Infection Research Articles

Efficacy and Safety of Add-on Parsaclisib to Ruxolitinib Therapy in Myelofibrosis Patients With Suboptimal Response to Ruxolitinib: Final Results From a Phase 2 Study

Background: Ruxolitinib (RUX) is a potent JAK1/JAK2 inhibitor and is effective in patients (pts) with myelofibrosis (MF). However, suboptimal or declining responses to RUX occur in a subset of pts, possibly due to persistent PI3K pathway activation with chronic JAK inhibitor therapy. Parsaclisib is a potent and highly selective next-generation PI3Kδ inhibitor. We conducted a phase 2 study (NCT02718300) evaluating add-on parsaclisib to stable doses of RUX, for pts with MF who experienced a suboptimal response to RUX (Yacoub A. HemaSphere 2021;5 Suppl 2:512). Here we report efficacy and safety results from the completed study. Methods: Eligible pts had primary or post-essential thrombocythemia/post-polycythemia vera MF with suboptimal response (palpable spleen >10 cm below left subcostal margin [LSM], or palpable splenomegaly 5-10 cm below LSM and presence of 1 symptom score ≥5 or 2 symptom scores ≥3 each using the Screening Symptom Form) after ≥6 months of RUX (5-25 mg twice daily; RUX stable dose, ≥8 wks). Pts remained on their stable RUX dose and were randomized to receive add-on parsaclisib 10 mg or 20 mg once daily (QD) for 8 wks and the same dose once weekly (QW) thereafter (QD/QW group), or parsaclisib 5 mg or 20 mg QD for 8 wks and 5 mg QD thereafter (all QD group) (Figure). Primary efficacy endpoint was change in spleen volume (SV) from baseline to wk 12 by MRI/CT scan. Key secondary endpoints included change in SV to wk 24, change in total symptom score (MFSAF-TSS, MPN-SAF-TSS), and safety. Results: Overall, 32 pts received parsaclisib QD/QW and 42 pts received parsaclisib all QD. Baseline median age was 68.0 (range 41.0-89.0) years and 47.3% of pts were male. The study has been completed. Median treatment duration was 336.5 days; median average daily dose was 5.0 mg/day for parsaclisib and 29.8 mg/day for RUX. Among all pts, 16 (21.6%) were rolled over to continue therapy in an open-label parsaclisib study after ending treatment in the present study. Other common reasons for pts discontinuing treatment were adverse events (13 [17.6%]) and progressive disease (10 [13.5%]); remainder discontinued for physician decision, pt decision, or "Other." Baseline median SV (cm3) was 2414.5 in QD/QW (n=29) and 1877.5 in QD (n=37); median MFSAF-TSS was 10.8 (n=28) and 16.3 (n=32) and median MPN-SAF-TSS was 25.5 (n=28) and 30.0 (n=37), respectively. Median percentage change in SV at wk 12 was −1.6 (n=28) in QD/QW and −15.4 (n=37) in QD, and at wk 24 was −2.5 (n=20) and −19.3 (n=29), respectively. Median percentage change in MFSAF-TSS at wk 12 was −14.0 (n=21) in QD/QW and −32.8 (n=24) in QD, and at wk 24 was −10.0 (n=16) and −44.4 (n=18), respectively. Median percentage change in MPN-SAF-TSS at wk 12 was −19.2 (n=20) in QD/QW and −39.8 (n=30) in QD, and at wk 24 was −43.3 (n=15) and −60.8 (n=26), respectively. Responder analysis for these 3 efficacy variables is shown in the Table. Nonhematologic treatment-emergent adverse events (TEAEs) were primarily grade 1/2. Grade 3/4 nonhematologic TEAEs occurring in >1 pt overall were pneumonia (n=5; 3 QD/QW, 2 QD), fatigue, hypoxia (each n=2; each 1 QD/QW, 1 QD), dyspnea (n=2, all QD), fall, alanine aminotransferase (ALT) increased, aspartate aminotransferase (AST) increased, hypocalcemia (each n=2; all QD/QW). New-onset grade 3 thrombocytopenia was observed in 6/32 pts (18.8%) in QD/QW and 11/42 pts (26.2%) in QD; grade 4 thrombocytopenia was observed in 6/32 pts (18.8%) in QD/QW and 3/42 pts (7.1%) in QD. TEAEs of special interest included grade ≥3 ALT and AST (each n=2; all QD/QW), grade ≥2 diarrhea (n=4) and rash (n=1) (all QD/QW), and any-grade herpes simplex (n= 4; 1 QD/QW, 3 QD) and VZV infection (n= 3; 1 QD/QW, 2, QD). No colitis was reported. TEAEs led to parsaclisib interruption in 16/32 pts in QD/QW and 22/42 pts in QD, and RUX interruption in 5/32 and 8/42 pts, respectively. TEAEs led to parsaclisib discontinuation in 5/32 pts in QD/QW and 4/42 pts in QD, and RUX discontinuation in 2/32 and 2/42 pts, respectively. Conclusion: Final results from the phase 2 study demonstrate improvement in symptoms and SV with add-on parsaclisib in patients with MF having a suboptimal response to ruxolitinib. All daily dosing regimens were more efficacious than daily/weekly dosing. Combination therapy was associated with limited grade 3/4 AEs and TEAE-related discontinuations. Phase 3 studies using 5 mg QD parsaclisib together with ruxolitinib in naive MF patients and ruxolitinib-experienced patients are in progress. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

A novel microarray-based PCR assay for the detection of HSV-1, HSV-2, and VZV skin infections: A retrospective analysis

Prevalence of HSV-1, HSV-2, and VZV infection ranges from 20% to 90%. Viral reactivation is common and results in a significant individual and socioeconomic burden. Pathognomonic skin manifestations are not always present, impairing definitive clinical diagnosis. We evaluated the performance of a novel microarray-based multiplex PCR system (Euroarray, Euroimmun Medizinische Labordiagnostika) for the molecular detection of these pathogens. In this retrospective study, 50 consecutive specimens positive for HSV-1, HSV-2, or VZV (pre-characterized by qPCR) were analyzed. Two hundred-and-five negative test results were applied as a control group. The microarray successfully detected the respective pathogens in all samples that yielded a qPCR quantifiable amount of DNA. Two and one specimens containing VZV and HSV-1 DNA beneath the limit of quantification tested microarray negative. Microarray specificity was 100%. The microarray is a useful tool for diagnosing viral infections of skin and mucous membranes, allowing rapid differentiation between three pathogens in a single assay.

Natural history of infants with non-SCID T cell lymphopenia identified on newborn screen

Newborn screening (NBS) for severe combined immunodeficiency (SCID) can identify infants with non-SCID T cell lymphopenia (TCL). The purpose of this study was to characterize the natural history and genetic findings of infants with non-SCID TCL identified on NBS. We analyzed data from 80 infants with non-SCID TCL in the mid-Atlantic region between 2012 and 2019. 66 patients underwent genetic testing and 41 (51%) had identified genetic variant(s). The most common genetic variants were thymic defects (33%), defects with unknown mechanisms (12%) and bone marrow production defects (5%). The genetic cohort had significantly lower median initial CD3+, CD4+, CD8+ and CD4/CD45RA+ T cell counts compared to the non-genetic cohort. Thirty-six (45%) had either viral, bacterial, or fungal infection; only one patient had an opportunistic infection (vaccine strain VZV infection). Twenty-six (31%) of patients had resolution of TCL during the study period.

Scalp necrosis during a giant cell arteritis relapse triggered by a VZV infection.

Scalp necrosis during a giant cell arteritis relapse triggered by a VZV infection.

Identifying optimal vaccination scenarios to reduce varicella zoster virus transmission and reactivation

BackgroundVaricella zoster virus (VZV) is one of the eight known human herpesviruses. Initial VZV infection results in chickenpox, while viral reactivation following a period of latency manifests as shingles. Separate vaccines exist to protect against both initial infection and subsequent reactivation. Controversy regarding chickenpox vaccination is contentious with most countries not including the vaccine in their childhood immunization schedule due to the hypothesized negative impact on immune-boosting, where VZV reactivation is suppressed through exogenous boosting of VZV antibodies from exposure to natural chickenpox infections.MethodsPopulation-level chickenpox and shingles notifications from Thailand, a country that does not vaccinate against either disease, were previously fitted with mathematical models to estimate rates of VZV transmission and reactivation. Here, multiple chickenpox and shingles vaccination scenarios were simulated and compared to a model lacking any vaccination to analyze the long-term impacts of VZV vaccination.ResultsAs expected, simulations suggested that an introduction of the chickenpox vaccine, at any coverage level, would reduce chickenpox incidence. However, chickenpox vaccine coverage levels above 35% would increase shingles incidence under realistic estimates of shingles coverage with the current length of protective immunity from the vaccine. A trade-off between chickenpox and shingles vaccination coverage was discovered, where mid-level chickenpox coverage levels were identified as the optimal target to minimize total zoster burden. Only in scenarios where shingles vaccine provided lifelong immunity or coverage exceeded current levels could large reductions in both chickenpox and shingles be achieved.ConclusionsThe complicated nature of VZV makes it impossible to select a single vaccination scenario as universal policy. Strategies focused on reducing both chickenpox and shingles incidence, but prioritizing the latter should maximize efforts towards shingles vaccination, while slowly incorporating chickenpox vaccination. Alternatively, countries may wish to minimize VZV complications of both chickenpox and shingles, which would lead to maximizing vaccine coverage levels across both diseases. Balancing the consequences of vaccination to overall health impacts, including understanding the impact of an altered mean age of infection for both chickenpox and shingles, would need to be considered prior to any vaccine introduction.

Ramsay Hunt syndrome

Ramsay-Hunt syndrome (RHS) is a disease caused by reactivation of varicella-zoster virus in the geniculate ganglion. It may be one of the common reasons of the facial palsy. Symptoms of the RHS include vesicular rash on the auricle, external auditory canal, soft palate, pharynx, facial nerve paralysis, ear pain, tinnitus, vertigo and hearing loss. There may be other symptoms connected to cranial nerves (CN) V, VIII, IX or X, when they are involved. Men are more likely to develop lesions than women. Risk of developing Ramsay-Hunt syndrome increases with age. Authors searched Google Scholar and PubMed, using searchterms Ramsay-Hunt syndrome, varicella-zoster virus, VZV, facial palsy. We manually searched the references of selected articles for additional relevant articles. We selected articles relevant to a general medicine readership and prioritised systematic reviews, clinical practice guidelines and cases. The literature contains the latest reports on Ramsay-Hunt syndrome. Clinicians should not ignore patients’ symptoms and always pay attention to possibility of VZV infection and the development of RHS, as treatment should be started within 72 hours after the onset of the symptoms. Main treatment includes antiviral drugs and corticosteroids. The results are promising.

Seropositivity, Risks, and Morbidity From Varicella-Zoster Virus Infections in an Adult PWH Cohort From 2000-2020.

BackgroundVaricella-zoster virus (VZV) infection disproportionately affects people with HIV (PWH), primarily presenting as herpes zoster. However, VZV seroprevalence, its association with zoster, and clinical outcomes remain understudied in era of modern antiretroviral therapy (ART). We assessed VZV seroprevalence, rates of VZV illness, and associated health care costs in a large cohort of PWH over 20 years.MethodsWe performed retrospective chart reviews of patients followed at a regional HIV clinic from January 1, 2000, to December 31, 2020. Serological, immunization, clinical, and costing data were extracted from in-house databases. VZV-related inpatient admissions, emergency department (ED), and urgent care (UC) visits were identified using relevant International Classification of Disease (ICD-10) codes and validated where possible by 2 physicians. Health care utilization costs were adjusted to 2020 Canadian dollars.ResultsOf 3006 PWH, VZV serology was available for 2628; of these, 2503 (95.2%) were seropositive. Only 39% of known seronegative patients were subsequently immunized for varicella. During 29 768 years of patient follow-up, 38 hospitalizations and 138 ED/UC visits due to VZV infection were identified. Most occurred in VZV-seropositive PWH <50 years of age (82%) who were unimmunized (99.2%) and not on ART (64.8%). Nearly 25% of hospitalizations were due to laboratory-confirmed VZV meningitis/encephalitis. The average admission cost was CDN$33 001; the total measured cost of VZV illness was CDN$1 258 718.ConclusionsDespite ART and vaccines for chickenpox and shingles, VZV still caused significant costs and morbidity for PWH, occurring at younger ages and often as encephalitis/meningitis. Supporting ART adherence may reduce VZV illness and hospitalization costs in PWH, and the cost-effectiveness of expanding shingles vaccine use warrants further study.

Early experience with varicella vaccination in pediatric heart transplant recipients.

International consensus guidelines to vaccinate children after solid organ transplant with the live-attenuated varicella (VZV) vaccine exclude pediatric heart transplant recipients due to insufficient evidence for safety, seroconversion rate, or adverse event profile. Caution is also recommended in the setting of mycophenolate mofetil (MMF) immunosuppression. However, VZV infection in these patients can be serious or even fatal. We report our novel early experience with VZV vaccination in a cohort of 31 children following heart transplantation, 42% of who were on MMF. The early seroconversion rate was 16/17 (94%) with no major adverse events. Though a rash of some description was reported in 29%, spots were few and self-resolving in 1-3 days. Select pediatric heart transplant patients can be safely vaccinated with VZV vaccine with a high early seroconversion rate and a mild adverse event profile.

Varicella-Zoster virus reactivation following severe acute respiratory syndrome coronavirus 2 vaccination or infection: New insights

IntroductionVaricella zoster virus (VZV) reactivation has been reported following vaccination for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), but the real extent remains unknown. MethodsWe conducted a systematic review to summarize evidence of VZV reactivation or infection following SARS-CoV-2 vaccination. Episodes after coronavirus disease-2019 (COVID-19) were also identified. Related articles were identified in PubMed and EMBASE databases till December 31, 2021 using the terms “varicella zoster” and “COVID-19″. PROSPERO Register Number: CRD42021289399. ResultsThe search revealed 314 articles, of which 55 met the inclusion criteria. VZV manifestations were documented in 179 (82.1%) subjects following SARS-CoV-2 vaccination and in 39 (17.9%) patients with COVID-19. Among the vaccinated, median (IQR) age was 56.5 (42–70) years, and 56.8% were female. Twenty-one (16.8%) were immunosuppressed. The median (IQR) latency time after vaccination was 6 (3–10) days, and 84.4% received mRNA vaccines. VZV reactivation occurred following a first dose (68.2%), a second dose (12.8%) or a booster (0.6%). The most important VZV manifestation was dermatome herpes zoster rash, which accounted for 86.4% of events in vaccinated subjects. Twenty patients (11.3%) presented serious VZV events after vaccination, with Herpes Zoster ophthalmicus (5.6%) and post-herpetic neuralgia (3.4%) predominating. No VZV pneumonia or deaths were recorded. Antiviral prescriptions were made in 96.2% of vaccinated subjects. No significant differences between vaccinated and infected subjects were found. ConclusionThis study indicates that the occurrence of VZV reactivation is clinically relevant. However, our findings suggest that COVID-19 vaccination is safe, and remains strongly recommended.

Acute myelitis with multicranial neuritis caused by Varicella zoster virus: a case report

BackgroundVaricella zoster virus (VZV) can remain lifelong in the latent state in ganglionic neurons and adrenal glands after the initial infection. However, it can be reactivated anytime and can trigger several severe neurological manifestations such as encephalitis, meningitis, Ramsay-Hunt syndrome, cerebellitis, myelitis, and stroke. In addition, due to the diversity of clinical manifestations, clinical diagnosis of VZV can be difficult, especially in the absence of varicella. Here, we describe the case of a 52-year-old male who presented with symptoms of acute myelitis as well as polycranial neuritis, and was finally diagnosed with VZV infection through metagenomic next-generation sequencing (mNGS).Case presentationA 52-year-old male came to our hospital with complaint of headache, fever, weakness of right lower limb, abdominal distension, and hearing loss. T2-weighted MRI revealed a hyperintense lesion in the spinal cord extending from T8 to T11. In addition, enhanced MRI showed small patches and strips hyperintensities in both the spinal cord and meninges. Plain abdominal radiographs and abdominal computed tomography (CT) scan displayed air-fluid levels and incomplete bowel obstruction. Moreover, electrophysiological evaluation of the peripheral neuropathy in the extremities was found to be normal. Finally, by using metagenomic next-generation sequencing (mNGS) we found that the copy number of VZV DNA in cerebrospinal fluid (CSF) was significantly increased and IgG antibody against VZV in CSF was also noted to be positive. Hence, VZV infection was identified in patient’s central neuron system. Finally, after a few days of low dose steroid treatment, the patient's symptoms were found to be significantly improved.ConclusionsThe findings indicate that we should pay proper attention to the various symptoms caused by VZV infection due to the clinical heterogeneity, especially in the absence of cutaneous lesions.

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid.

BackgroundVZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown.MethodsThis is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta.ResultsSeventy‐two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty‐two patients completed follow‐up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd‐ratio (OR) 3.1 [1.4–8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4–181] p = .001, OR 6.2 [1.3–33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta.ConclusionsNeurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.

Lyme Borreliosis Associated with Ramsay-Hunt Syndrome: A Case Presentation of Bilateral Facial Nerve Palsy in a 14-Year-Old Patient

Background: In children, facial neuropathy is the most common disease that occurs due to the damage of the cranial nerves. Facial nerve palsy (FNP) in children can be congenital or acquired. Congenital FNP may occur at birth due to the trauma and with certain genetic syndromes. Acquired FNP can be caused by HSV types 1,2, HHV-6, cytomegalovirus, EBV, VZV, bacterium B. burgdorferi or can result from inflammatory diseases, trauma and tumors. Unilateral or bilateral FNP is the most common complication of Lyme disease in children. The study that was conducted by Furuta Y. et al. indicates that reactivation of VZV infection is an important cause of acute peripheral FNP in children aged 6-15 years. Case Report: We have described a rare clinical case of bilateral peripheral FNP in a 14-year-old child with a confirmed diagnosis of Lyme disease and reactivation of VZV infection. Conclusions: Prescribed therapy with doxycycline for 21 days and valaciclovir for 7 days made it possible to achieve functional recovery of nerve on both sides.

Encephalitis, meningitis, and acute cerebellar ataxia as neurological complications of VZV infection in children. A retrospective study

Encephalitis, meningitis, and acute cerebellar ataxia as neurological complications of VZV infection in children. A retrospective study

Anti-varicella zoster virus and related anti-inflammation effects of ethanolic extract of Elaeocarpus sylvestris

Ethnopharmacological relevanceElaeocarpus sylvestris var. ellipticus (ES), a plant that grows in Taiwan, Japan, and Jeju Island in Korea. ES root bark, known as “sanduyoung,” has long been used in traditional oriental medicine. ES is also traditionally used to treat anxiety, asthma, arthritis, stress, depression, palpitation, nerve pain, epilepsy, migraine, hypertension, liver diseases, diabetes, and malaria. However, lack of efficacy and mechanism studies on ES. Aim of the studyIn the present study, we aim to investigate the VZV-antiviral efficacy, pain suppression, and the anti-inflammatory and antipyretic effects of ES. Methodsand methods: Inhibition of VZV was evaluated by hollow fiber assays. Analgesic and antipyretic experiments were conducted using ICR mice and SD Rats, and anti-inflammatory experiments were conducted using Raw264.7 cells. ResultsTo evaluate the efficacy of ESE against VZV, we conducted antiviral tests. ESE inhibited cell death by disrupting virus and gene expression related to invasion and replication. In addition, ESE suppressed the pain response as measured by writhing and formalin tests and suppressed LPS-induced inflammatory fever. Further, ESE inhibited the phosphorylation of IκB and NF-κB in LPS-induced Raw264.7 cells and expression of COX-2, iNOS, IL-1β, IL-6, and TNF-α. ConclusionE. sylvestris shows potential as a source of medicine. ESE had a direct effect on VZV and an inhibitory effect on the pain and inflammation caused by VZV infection.

A case of paraplegia due to asymptomatic varicella-zoster virus infection in AIDS patient unexpectedly diagnosed by CSF metagenomic next-generation sequencing

BackgroundVaricella-zoster virus (VZV) infection may induce central nervous system complications in HIV/AIDS patients. However, it is rare to have paraplegia caused by VZV infection but no herpes zoster clinically. Asymptomatic VZV infection in HIV/AIDS patient increased the difficulty of diagnosis.Case presentationWe reported a 41-year-old male AIDS patient with rare asymptomatic VZV infection-induced paraplegia after his anti-retroviral therapy initiation. MRI of the spinal cord showed the morphology of the thoracic spinal cord was irregular and locally inflated. The patient was confirmed as VZV induced thoracic myelomyelitis by using the cerebrospinal fluid for metagenomic next-generation sequencing (mNGS).ConclusionsmNGS may contribute to disease diagnosis for asymptomatic VZV infection-induced myelitis.

Clinical presentation and course of multiple sclerosis in patients with herpesvirus infection

To date, the features of clinical presentation, course, and the effectiveness of therapy for multiple sclerosis (MS) in the presence of persistent herpesvirus infection (PHVI) remain poorly understood.Objective: to evaluate the features of clinical presentation and course of MS in patients with PHVI to optimize patient management.Patients and methods. We examined 122 patients with a clinically definite diagnosis of MS according to McDonald criteria (2010) (82 women and 40 men, age: 18–50 years, mean age – 37.74±11.04 years). MS duration at the time of examination was from 6 months to 20 years (mean – 8.53±7.47 years), mean Expanded Disability Status Scale (EDSS) score – 2.91±1.67. 86% of patients had relapsing-remitting MS; 14% – secondary progressive MS. 98 (80%) patients received disease modifying therapies (DMTs). All patients underwent a comprehensive clinical and neurological examination, magnetic resonance imaging (MRI). 30 healthy donors (20 women and 10 men, age: 19–62 years, mean age: 39.1±12.1 years) were included in the control group. Serum levels of type-specific IgM and IgG antibodies to herpes simplex virus (HSV) 1, 2, 6, Varicella zoster virus (VVZ), Epstein–Barr virus (EBV), cytomegalovirus (CMV) were detected, in some patients – blood and cerebrospinal fluid (CSF) polymerase chain reaction, serum and CSF oligoclonal IgG.Results and discussion. We identified two sub-groups of MS patients: with PHVI reactivation (main group, n=29) and without it (comparison group, n=93). There were a significantly higher VZV (72%) and EBV infection rate (100%) in MS patients compared to the control group (50% and 83%, respectively). Mixed herpesvirus infection prevailed over mono-infection in MS patients. In contrast to controls, the most common viral pattern in MS group was a combination of 4 herpes viruses: HSV 1, 2 + VZV + EBV + CMV (χ2=3.9; p&lt;0.05). Patients in the main group had an unfavorable disease course: earlier MS onset, predominantly polysymptomatic onset, significantly higher relapse rate, faster disease progression, and higher EDSS and Functional Systems Scale (FSS) scores (p &lt;0.05). MRI activity was also associated with EBV infection: new T1Gd+ and T2 foci were associated with an increase in VCA-IgM to EBV level. We also observed decreased DMTs effectiveness (χ2=4,6; p=0,033) and worse DMTs tolerability (χ2=5,3; p=0,022) in the main group.Conclusion. MS patients with PHVI reactivation, have a more unfavorable course of the demyelinating process and, therefore, a greater degree of disability, compared with age-adjusted patients without a viral infection and the same disease duration.

Overwhelming Evidence for a Major Role for Herpes Simplex Virus Type 1 (HSV1) in Alzheimer's Disease (AD); Underwhelming Evidence against.

This review describes investigations of specific topics that lie within the general subject of HSV1’s role in AD/dementia, published in the last couple of years. They include studies on the following: relationship of HSV1 to AD using neural stem cells; the apparent protective effects of treatment of HSV1 infection or of VZV infection with antivirals prior to the onset of dementia; the putative involvement of VZV in AD/dementia; the possible role of human herpes virus 6 (HHV6) in AD; the seemingly reduced risk of dementia after vaccination with diverse types of vaccine, and the association shown in some vaccine studies with reduced frequency of HSV1 reactivation; anti-HSV serum antibodies supporting the linkage of HSV1 in brain with AD in APOE-ε4 carriers, and the association between APOE and cognition, and association of APOE and infection with AD/dementia. The conclusions are that there is now overwhelming evidence for HSV1’s role—probably causal—in AD, when it is present in brain of APOE-ε4 carriers, and that further investigations should be made on possible prevention of the disease by vaccination, or by prolonged antiviral treatment of HSV1 infection in APOE-ε4 carriers, before disease onset.

An Overview of Herpes zoster: Aetiology, Pathogenesis and Treatment

Varicella zoster virus is one of the eight herpes viruses that are pathogenic only for humans. It is alpha-herpes zoster of the genus varicellovirus, which causes varicella (chickenpox) and zoster (shingles). Herpes zoster is described as a multivesicular eruptive rash that follows a single or multiple adjacent dermatomal distribution. VZV infection begins with replication in epithelial cells of upper respiratory mucosa, which is followed by widely distributed vesicular rash. Cell-mediated immunity plays a role in this reactivation. Patients with conditions that decrease cell-mediated immunity are 20 to 100 times more prone to develop herpes zoster. It is often accompanied by acute pain and itchiness. Complications may be dermatological (e.g. secondary bacterial infection), neurological (e.g. long-term pain, segmental paresis, stroke), ophthalmological (e.g. keratitis, iridocyclitis, secondary glaucoma) or visceral (e.g. pneumonia, hepatitis). Most common Complications of the infection are post herpetic neuralgia and ophthalmic zoster. Treatment includes antiviral medications such as acyclovir, famciclovir, and valacyclovir given within 72 hours of symptom has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia, both these diseases are vaccine preventable. Before the invention of the recombinant VZV vaccine, live VZV vaccine was the recommended immunization, approved for adults 50 years and older.

POS-724 THROMBOTIC MICROANGIOPATHY AND EBV RELATED POST-TRANSPLANT LYMPHOPROLIFERATIVE DISORDER IN A YOUNG PATIENT: A CASE REPORT

Post-transplant lymphoproliferative disorders (PTLD) are recognized as a devastating complication of organ transplantation. In kidney transplants the incidence is estimated between 1 and 2%. They have been closely associated with Epstein-Barr virus (EBV), and the spectrum of manifestations after transplantation range from an infectious mononucleosis-like syndrome to more serious polyclonal or monoclonal lymphoproliferation. Herein we report a case of an EBV associated PLTD in a young patient A 12 years old boy received a paternal renal transplant for kidney failure secondary to Ig A nephropathy in december 2012. They both had old immunity (IgG positif and IgM negatif) to EBV. They had 3 mismatchs and the induction treatment was based on basiliximab, ciclosporin and steroids , the maintenance therapy consisted of ciclosporine, prednisone and MMF Post tranplant complications were marked by the onset of a VZV infection after 2 months which responded well to aciclovir treatment On october 2013, he was admitted to the transplant unit for exploration of an alteration in graft function and thrombopenia ; initlaly he was treated as an acute rejection by solumedrol boli and a biopsy of the graft was performed. The C2 dosage of ciclosporin returned very high being in the zone of toxicity and the result of the biopsy confirming it with the diagnosis of a thrombotic microangiopathy (TMA) secondary to anti calcineurins (ciclosporin) After 1 month , the patient presented episodes of rectal bleeding with gastrointestinal fibroscopy and left colonsocpy returned to normal with fever, earaches and elevated LDH without alteration of the graft’s function A specialized examination was performed objectifying a bilateral sero mucous otitis and we completed with a pelvic thoraco abdomino and cavum CT scan which showed multiple cervical and inguinal lymphadenopathy with nodular splenomegaly and the EVB pcr came back positive We completed with a fine needle aspiration and lymph node biospy diagnosing a lymph node localisation of diffuse large B cell lymphoma . Initial management consisted on withdrawl of immunosuppression and the prescription the chimeric anti-CD20 monoclonal antibody rituximab and transfusion of platelet pellets but the patient presented a severe thrombocytopenia with alteration of neurological condition secondary to meningeal haemorrhage and the result was fatal. Although the induction treatment in our case was based on basiliximab and the patient was Ig G positif to EBV before transplatation , he presented a severe form of an EBV related PLTD.

The Fate of Speckled Protein 100 (Sp100) During Herpesviruses Infection.

The constitutive expression of Speckled-100 (Sp100) is known to restrict the replication of many clinically important DNA viruses. This pre-existing (intrinsic) immune defense to virus infection can be further upregulated upon interferon (IFN) stimulation as a component of the innate immune response. In humans, Sp100 is encoded by a single gene locus, which can produce alternatively spliced isoforms. The widely studied Sp100A, Sp100B, Sp100C and Sp100HMG have functions associated with the transcriptional regulation of viral and cellular chromatin, either directly through their characteristic DNA-binding domains, or indirectly through post-translational modification (PTM) and associated protein interaction networks. Sp100 isoforms are resident component proteins of promyelocytic leukemia-nuclear bodies (PML-NBs), dynamic nuclear sub-structures which regulate host immune defenses against many pathogens. In the case of human herpesviruses, multiple protein antagonists are expressed to relieve viral DNA genome transcriptional silencing imposed by PML-NB and Sp100-derived proteinaceous structures, thereby stimulating viral propagation, pathogenesis, and transmission to new hosts. This review details how different Sp100 isoforms are manipulated during herpesviruses HSV1, VZV, HCMV, EBV, and KSHV infection, identifying gaps in our current knowledge, and highlighting future areas of research.