Varicella Zoster Infection Research Articles

The safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade: an international survey

BackgroundWithholding live-attenuated vaccines in patients using interleukin (IL)-1 or IL-6 blocking agents is recommended by guidelines for both pediatric and adult rheumatic diseases, since there is a risk of infection in an immune suppressed host. However, this has never been studied. This retrospective, multicenter survey aimed to evaluate the safety of live-attenuated vaccines in patients using IL-1 or IL-6 blockade.MethodsWe contacted physicians involved in the treatment of autoinflammatory diseases to investigate potential cases. Patients were included if a live-attenuated vaccine had been administered while they were on IL-1 or IL-6 blockade.ResultsSeventeen patients were included in this survey (7 systemic juvenile idiopathic arthritis (sJIA), 5 cryopyrin associated periodic syndrome (CAPS), 4 mevalonate kinase deficiency (MKD) and 1 familial Mediterranean fever (FMF). Three patients experienced an adverse event, of which two were serious adverse events (a varicella zoster infection after varicella zoster booster vaccination, and a pneumonia after MMR booster). One additional patient had diarrhea after oral polio vaccine. Further, seven patients experienced a flare of their disease, which were generally mild. Eight patients did not experience an adverse event or a flare.ConclusionWe have described a case series of seventeen patients who received a live-attenuated vaccine while using IL-1 or IL-6 blocking medication. The findings of this survey are not a reason to adapt the existing guidelines. Prospective trials are needed in order to acquire more evidence about the safety and efficacy before considering adaptation of guidelines.

Fatal visceral disseminated varicella zoster infection during initial remission induction therapy in a patient with lupus nephritis and rheumatoid arthritis\u2014possible association with mycophenolate mofetil and high-dose glucocorticoid therapy: a case report

BackgroundVisceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient.Case presentationA 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C). Although initial remission-induction therapy with prednisolone and tacrolimus was started, her serum creatinine level and urinary protein excretion were elevated. Methylprednisolone pulse therapy was added, and tacrolimus was switched to MMF. Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed. Laboratory examinations demonstrated rapid exacerbation of severe acute liver failure and coagulation abnormalities despite immediate multidisciplinary treatment, and she died of hemorrhagic shock 7 days after the onset of abdominal pain. A serum sample collected at the time of admission revealed that she had recursive VZV infection.ConclusionsMMF together with high-dose glucocorticoid therapy may increase the risk of VZV infection in Asian patients with SLE. Accumulation of evidence for parameters of safety, such as the area under the blood concentration–time curve of mycophenolic acid, should be urgently considered in order to establish a safer protocol for remission induction therapy in Asian patients with LN.

Varicella Pneumonia: Case Report and Review of a Potentially Lethal Complication of a Common Disease.

Varicella zoster virus causes varicella (chickenpox). It can be reactivated endogenously many years later to cause herpes zoster (shingles). Although varicella is usually a benign disease in healthy children, it resulted in over 11 000 hospitalizations and over 100 deaths every year, in all ages, in the United States. Morbidity was considerably worse in older teenagers and adults. Between 5% and 15% of cases of adult chickenpox will produce some form of pulmonary illness. Progression to pneumonia risk factors include pregnancy, age, smoking, chronic obstructive pulmonary disease, and immunosuppression. Typically, pulmonary symptoms occur 1 to 6 days after varicella zoster infection. They often include cough, fever, and dyspnea. Treatment is a 7-day course of intravenous acyclovir for varicella pneumonia. Early intervention may modify the course of this complication. This review illustrates practical features with a case of a 34-year-old female with severe varicella pneumonia. Despite the lack of significant past medical history and absence of immunosuppression, her pneumonia worsened and by using continuous positive airway pressure mask, intubation was avoided. More important, the radiographic progression of severe varicella pneumonia is shown. This highlights how a common disease of varicella can progress in an adult and manifest with significant organ malfunction.

Acute Disseminated Encephalomyelitis: A Rare Complication of Varicella Zoster Infection in an Adult

Acute Disseminated Encephalomyelitis: A Rare Complication of Varicella Zoster Infection in an Adult

Herpes zoster presenting as unilateral vasculitis

Vasculitis can be a primary disorder or a cutaneous manifestation of a viral infection. The present case describes an atypical localized cutaneous varicella-zoster virus infection inducing a small vessel vasculitis in a patient with multisystem sarcoidosis. Additionally, we discuss the differential diagnoses and treatment options. Varicella-Zoster infection occurs more frequently in immunosuppressed populations and can present with uncharacteristic clinical manifestations complicating the diagnosis as in the present case.

Immune Thrombocytopenic Purpura Secondary to Varicella Zoster Infection: A Case Report

Varicella zoster infection is usually considered to be benign despite of serious complications. Immune Thrombocytopenic Purpura (ITP) is usually a self-limiting disorder in children. ITP is an autoimmune disorder in which antibody-coated or immune complex–coated platelets are destroyed prematurely by the reticuloendothelial system, resulting in peripheral thrombocytopenia. In primary ITP the thrombocytopenia is isolated, whereas in secondary ITP the condition is associated with other disorders (e.g. Systemic Lupus Erythematous, HIV, VZV). We describe a case of immune Thrombocytopenic Purpura secondary to varicella infection in a previously healthy 7-y-old boy. He was treated successfully with intravenous immunoglobulin (IVIG).

Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection.

Varicella-zoster virus (VZV) is highly cell associated when grown in culture and has a much higher (4,000- to 20,000-fold increased) particle-to-PFU ratio in vitro than herpes simplex virus (HSV). In contrast, VZV is highly infectious in vivo by airborne transmission. Neurons are major targets for VZV in vivo; in neurons, the virus can establish latency and reactivate to produce infectious virus. Using neurons derived from human embryonic stem cells (hESC) and cell-free wild-type (WT) VZV, we demonstrated that neurons are nearly 100 times more permissive for WT VZV infection than very-early-passage human embryonic lung cells or MRC-5 diploid human fibroblasts, the cells used for vaccine production or virus isolation. The peak titers achieved after infection were ∼10-fold higher in human neurons than in MRC-5 cells, and the viral genome copy number-to-PFU ratio for VZV in human neurons was 500, compared with 50,000 for MRC-5 cells. Thus, VZV may not necessarily have a higher particle-to-PFU ratio than other herpesviruses; instead, the cells previously used to propagate virus in vitro may have been suboptimal. Furthermore, based on electron microscopy, neurons infected with VZV produced fewer defective or incomplete viral particles than MRC-5 cells. Our data suggest that neurons derived from hESC may have advantages compared to other cells for studies of VZV pathogenesis, for obtaining stocks of virus with high titers, and for isolating VZV from clinical specimens.IMPORTANCE Varicella-zoster virus (VZV) causes chickenpox and shingles. Cell-free VZV has been difficult to obtain, both for in vitro studies and for vaccine production. While numerous cells lines have been tested for their ability to produce high titers of VZV, the number of total virus particles relative to the number of viral particles that can form plaques in culture has been reported to be extremely high relative to that in other viruses. We show that VZV grows to much higher titers in human neurons than in other cell types in vitro and that the number of total virus genomes relative to the number of viral particles that can form plaques in culture is much lower in human neurons than other cultured cells. These findings indicate that human neurons may be useful for studying VZV in vitro, for growing preparations of virus with high titers, and for isolating the virus from human samples.

Multidermatomal Herpes Zoster in an Immunocompromised Patient-A Case Report

Multi-dermatomal involvement is uncommon in varicella zoster infection and indicates underlying immunosuppression. A 43 years old male, a known diabetic presented with painful papulovesicular lesions over the left side of the chest, back, arms and forearm with the history of chickenpox one month back. On evaluation for an unusual presentation, he was found to be reactive to HIV. Diagnosis of HZ was confirmed by HZV PCR. He was treated with antivirals, insulins, pain management and care of the lesions. The occurrence of the multi dermatomal herpes zoster with bilaterally symmetrical involvement immediately the following chickenpox is a rare observation and needs to be reported.

Acute Retinal Necrosis Secondary to Varicella Zoster Infection in a Immunocompromised Patient Post Lung Transplantation

Acute Retinal Necrosis Secondary to Varicella Zoster Infection in a Immunocompromised Patient Post Lung Transplantation

Disseminated herpes zoster causing acute respiratory distress syndrome in an immunocompetent patient

Disseminated cutaneous varicella herpes zoster with visceral involvement is rare and seen almost exclusively in immunocompromised patients. We describe an unusual case of fulminant herpes zoster (HZ) in a healthy,...

Post-Varicella Acute In ammatory Demyelinating Polyradiculoneuropathy in a 51-year old Filipino Male: A Case Report

Primary varicella zoster infection is commonly observed in school-aged children. There are increasing reports of adults being affected. Varicella zoster infection has a myriad of clinical complication. The rarer of these complications is GuillanBarre syndrome (GBS) or acute inflammatory demyelinatimgpolyradiculoneuropathy, with less than 50 cases in reported literature. Keywords: varicella, acute inflammatory demyelinating polyradiculoneuropathy, GuillanBarre Syndrome

Role of the JNK Pathway in Varicella-Zoster Virus Lytic Infection and Reactivation.

Mechanisms of neuronal infection by varicella-zoster virus (VZV) have been challenging to study due to the relatively strict human tropism of the virus and the paucity of tractable experimental models. Cellular mitogen-activated protein kinases (MAPKs) have been shown to play a role in VZV infection of nonneuronal cells, with distinct consequences for infectivity in different cell types. Here, we utilize several human neuronal culture systems to investigate the role of one such MAPK, the c-Jun N-terminal kinase (JNK), in VZV lytic infection and reactivation. We find that the JNK pathway is specifically activated following infection of human embryonic stem cell-derived neurons and that this activation of JNK is essential for efficient viral protein expression and replication. Inhibition of the JNK pathway blocked viral replication in a manner distinct from that of acyclovir, and an acyclovir-resistant VZV isolate was as sensitive to the effects of JNK inhibition as an acyclovir-sensitive VZV isolate in neurons. Moreover, in a microfluidic-based human neuronal model of viral latency and reactivation, we found that inhibition of the JNK pathway resulted in a marked reduction in reactivation of VZV. Finally, we utilized a novel technique to efficiently generate cells expressing markers of human sensory neurons from neural crest cells and established a critical role for the JNK pathway in infection of these cells. In summary, the JNK pathway plays an important role in lytic infection and reactivation of VZV in physiologically relevant cell types and may provide an alternative target for antiviral therapy.IMPORTANCE Varicella-zoster virus (VZV) has infected over 90% of people worldwide. While primary infection leads to the typically self-limiting condition of chickenpox, the virus can remain dormant in the nervous system and may reactivate later in life, leading to shingles or inflammatory diseases of the nervous system and eye with potentially severe consequences. Here, we take advantage of newer stem cell-based technologies to study the mechanisms by which VZV infects human neurons. We find that the c-Jun N-terminal kinase (JNK) pathway is activated by VZV infection and that blockade of this pathway limits lytic replication (as occurs during primary infection). In addition, JNK inhibition limits viral reactivation, exhibiting parallels with herpes simplex virus reactivation. The identification of the role of the JNK pathway in VZV infection of neurons reveals potential avenues for the development of alternate antiviral drugs.

Eosinophilic dermatosis of hematologic malignancy mimicking varicella zoster infection: report in a woman with chronic lymphocytic leukemia and review of the literature

Eosinophilic dermatosis of hematologic malignancy is a rare papulovesicular eruption that presents in patients with hematoproliferative disorders, particularly chronic lymphocytic leukemia. A 59-year-old woman with chronic lymphocytic leukemia who developed eosinophilic dermatosis of hematologic malignancy mimicking varicella zoster infection is described. PubMed database was searched with the key words: chronic, dermatosis, eosinophilic, hematologic, infection, leukemia, lymphocytic, malignancy, varicella, zoster. The papers generated by the search and their references were reviewed. The patient presented, on more than 20 occasions, with a dermatomal vesicular eruption. Her oncologist, based on the clinical presentation, treated each episode as recurrent varicella zoster virus infection. A complete workup of the patient not only demonstrated negative viral studies but also revealed pathologic changes consistent with eosinophilic dermatosis of hematologic malignancy on lesional skin biopsy. The recurrence of the patient’s dermatosis was less frequent when her malignancy was under better control. Eosinophilic dermatosis of hematologic malignancy may mimic other reactive dermatoses. The morphology of our patient’s recurrent dermatosis resembled varicella zoster virus infection. Disseminated zoster virus infection with dermatomal and non-dermatomal distribution should be added to the clinical differential diagnosis of eosinophilic dermatosis of hematologic malignancy.

Case Report Ramsay Hunt Syndrome presenting as “a window’’ to HIV diagnosis in 48 year old African female: A case report

Background: Ramsay Hunt Syndrome in adults is reported in a number of case reports as an uncommon presentation of Varicella zoster Virus infection. Ramsay Hunt Syndrome occurs when there is reactivation of the latent Varicella zoster virus present in the ganglia due to previous varicella infection. Following a breakdown of the immune system, latent Varicella zoster infection can be activated. HIV (Human Immunodeficiency Virus infection), causes immunosuppression and hence reactivation of Varicella zoster. The diagnosis of Ramsay Hunt Syndrome, gives a window of opportunity to investigate for HIV. Here we report our first case of Ramsay Hunt syndrome as a presenting feature of HIV disease in an apparently healthy looking 48 year old black African female who was unaware of her HIV status at the time of presentation.
 This case is reported in order to highlight the need to use Ramsay Hunt Syndrome as a window of opportunity to screen for underlying HIV.
 Case presentation: A 48 year old black African female who was unaware of her HIV status, presented to our outpatients department with a two day history of painful right ear pain, vesicles on the right pinna and inability to completely close her right eye, her mouth was deviated to the left, with a wrinkle free frown. She denied any alteration in taste sensation and hyperacusis. She had a grade IV House-Brackmann facial paralysis.A diagnosis of Ramsay Hunt Syndrome was made and an HIV test was offered, the test was positive for HIV.A subsequent HAART (Highly Active Antiretroviral Therapy) work up, revealed CKD 3B (Chronic Kidney Disease stage 3B) and a CD4 (cluster of differentiation 4) count of 217 cells/µl .She was started on antiretroviral therapy 2 weeks after completing a 10 day regimen of acyclovir. In addition to her drug treatment she received ocular care and physiotherapy. Four months on her facial nerve function has improved modestly.
 Conclusion: An HIV test should be an indispensable part of the Ramsay Hunt syndrome workup, as its diagnosis gives a window of opportunity to diagnose HIV and offer life- saving HAART.

Can a healthcare worker be a source of an infection of a patient – a risk of transmitting the chickenpox and shingles virus VZV by the staff of hospital wards – preliminary research findings.

Introduction. Chickenpox is a highly infectious disease, caused by the Varicella-zoster virus. An infection during pregnancy poses particular risk, as it may have serious consequences for both the pregnant woman and the fetus. The only effective and safe method of preventing chickenpox is protective vaccination.Aim. This study aims to assess the risk of contracting the Varicella-zoster infection in a selected population of hospital workers, as well as the further transmission of the virus to newborns, mothers and older children.Materials and Methods. A survey was conducted in September 2014 in three public hospitals in Poznań, among nurses and midwives working in paediatric, neonatal and maternity wards. 136 nurses and midwives participated in the survey.Results. The analysis of the findings reveals that 114 staff members of the hospital wards, i.e. 83.82%, have had chickenpox in the past, 14 respondents (10.29%) have never had this illness, and 8 (5.88%) do not know if they have been ill, which means that 16% of the respondents could potentially contract chickenpox. For the majority of nurses and midwives (103) the infection had taken place before they started work. However, 11 respondents (8,08) were infected during employment.Conclusions. 1) Nearly one out of 4 hospital staff members had no history of chickenpox contraction at the beginning of their employment. 2) Nearly 15% of the workers confirm that at the beginning of employment their immunity status was established on the basis of an interview. 3) The majority of employees negatively interviewed for chickenpox history have not been recommended to be vaccinated against this disease.

Infections in Hematopoietic Cell Transplant Recipients: Results From the Organ Transplant Infection Project, a Multicenter, Prospective, Cohort Study.

BackgroundInfection is a major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Our object was to better define the epidemiology and outcomes of infections after HCT.MethodsThis was a prospective, multicenter cohort study of HCT recipients and conducted from 2006 to 2011. The study included 4 US transplant centers and 444 HCT recipients. Data were prospectively collected for up to 30 months after HCT using a standardized data collection tool.ResultsThe median age was 53 years, and median follow up was 413 (range, 5–980) days. The most common reason for HCT was hematologic malignancy (87%). The overall crude mortality was 52%. Death was due to underlying disease in 44% cases and infection in 21%. Bacteremia occurred in 231 (52%) cases and occurred early posttransplant (median day 48). Gram-negative bloodstream infections were less frequent than Gram-positive, but it was associated with higher mortality (45% vs 13%, P = .02). Clostridium difficile infection developed in 148 patients (33%) at a median of 27 days post-HCT. There were 53 invasive fungal infections (IFIs) among 48 patients (11%). The median time to IFI was 142 days. Of 155 patients with cytomegalovirus (CMV) infection, 4% had CMV organ involvement. Varicella zoster infection (VZV) occurred in 13 (4%) cases and was disseminated in 2. Infection with respiratory viruses was seen in 49 patients. Pneumocystis jirovecii pneumonia was rare (1%), and there were no documented cases of nocardiosis, toxoplasmosis, endemic mycoses, or mycobacterial infection. This study lacked standardized antifungal and antiviral prophylactic strategies.ConclusionsInfection remains a significant cause of morbidity and mortality after HCT. Bacteremias and C difficile infection are frequent, particularly in the early posttransplant period. The rate of IFI is approximately 10%. Organ involvement with CMV is infrequent, as are serious infections with VZV and herpes simplex virus, likely reflecting improved prevention strategies.

Varicelle et grossesse.

Varicella-zoster primary infection in a pregnant woman is an uncommon occurrence in France, but can cause concern for patients and for clinicians. Varicella (chickenpox) is usually benign, but can have serious consequences for the mother (especially in the third trimester of pregnancy), for the fetus (risk of fetal varicella syndrome particularly if maternal primary infection occurs before 20weeks of gestation), and for the newborn (risk of congenital neonatal varicella if the mother is infected in the peripartum period). Several diagnostic tools, prophylaxis measures and antiviral treatments are currently available and help in the management of varicella during pregnancy.

Quality Assessment of Process Measures in Antimicrobial Stewardship: Concordance of Valacyclovir Indication and Automatic Prospective Approval in Computerized Provider Order Entry

BackgroundThe Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America (SHEA) recommend computerized decision support at the time of prescribing as an antimicrobial stewardship (AST) tool. Providing antimicrobial indications during prescribing can optimize infection-specific therapy through appropriate antimicrobial selection, dosing, and frequency. The Leapfrog group identifies this as a quality measure for their report card system. At Beth Israel Deaconess Medical Center (BIDMC), indication-based dosing has been incorporated in the computerized provider order entry (CPOE) system since 2006. At BIDMC, valacyclovir is only approved for the treatment of varicella zoster (VZV) infection or prophylaxis of solid organ transplant (SOT) patients at low risk for cytomegalovirus. These indications bypass the need for AST approval. Accuracy validation of the selected indications has not been formally performed.MethodsA retrospective chart review was performed in patients prescribed valacyclovir during an 8-month period in 2016. Electronic medical records, laboratory reports, and pharmacy records were reviewed to identify the suspected/confirmed infection. The primary outcome was the concordance rate of selected CPOE valacyclovir indication compared with suspected/confirmed infection at the time of ordering. The secondary outcome was the proportion of valacyclovir use per institutional protocol.ResultsOverall, 117 patients were included, with a median age of 57.9 years, 51 (43.6%) were male, and 4 (3.4%) were located in an intensive care unit. Fifty-nine orders (50.4%) selected VZV as the indication, followed by 21 orders (17.9%) for SOT prophylaxis. Of orders with any CPOE indication, only 59/101 (58.4%) were concordant with suspected/confirmed infection. Of the valacyclovir orders with a VZV indication, 37 (62.7%) were concordant. Of the orders with SOT prophylaxis indications, 5 (23.8%) were concordant. Furthermore, only 46 orders (39.3%) were per BIDMC-protocol.ConclusionConcordance of CPOE indication selection and suspected/confirmed infection for valacyclovir was low. Using CPOE to grant automatic prospective approval must be monitored and audited for accuracy if employed as an AST tool.Disclosures All authors: No reported disclosures.

Deficit of Anterior Pituitary Function and Variable Immune Deficiency Syndrome: A Novel Mutation.

Common variable immunodeficiency (CVID) is a complex primary immunodeficiency disorder with hypogammaglobulinemia as a major feature. Most of the patients do not have a specific genetic abnormality. Autoimmune disorders occur commonly in patients with CVID. We report a case of a girl with secondary adrenal insufficiency who developed a disseminated varicella zoster infection and zoster meningoencephalitis with vaccine strain. The laboratory evaluation of this patient led to the final diagnosis of CVID with a new variant of TACI (transmembrane activator and calcium-modulator and cyclophilin ligand interactor) mutation and DAVID syndrome (deficit of anterior pituitary function and variable immune deficiency).1

Idiopathic intracranial hypertension following varicella zoster infection in a young adult

Abstract Varicella zoster virus (VZV) can present with multiple neurological complications both during and in the immediate post-infectious period. Among these, idiopathic intracranial hypertension (IIH) is a rare but treatable entity exclusively reported in children and adolescents. This report describes a 23 year old female who developed headache and visual disturbances on the third week after the exanthema, who satisfied the diagnostic criteria for IIH. Clinical improvement was achieved with medical management. To the best of our knowledge, this is the first report of IIH in an adult patient following varicella infection.