Full-Genome Sequence of a Novel Varicella-Zoster Virus Clade Isolated in Mexico

PubMed Central

Rodríguez-Castillo, Araceli; Ortiz-Alcántara, Joanna María; Gonzalez-Durán, Elizabeth; Segura-Candelas, José Miguel; Pérez-Agüeros, Sandra Ivette; Escobar-Escamilla, Noé; Méndez-Tenorio, Alfonso; Diaz-Quiñonez, José Alberto

2015-01-01

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, which causes varicella (chicken pox) and herpes zoster (shingles) in humans. Here, we report the complete genome sequence of varicella-zoster virus, isolated from a vesicular fluid sample, revealing the circulation of VZV clade VIII in Mexico. PMID:26159533

Antibody class capture assays for varicella-zoster virus.

PubMed Central

Forghani, B; Myoraku, C K; Dupuis, K W; Schmidt, N J

1984-01-01

Pooled monoclonal antibodies to varicella-zoster virus (VZV) were used as "detector" antibodies in a four-phase enzyme immunofluorescence assay for determination of immunoglobulin M (IgM), IgA, and IgG antibodies to VZV. Polyclonal antisera specific for heavy chains of human IgM, IgA, and IgG were employed as "capture" antibodies on the solid phase. The antibody class capture assay (ACCA) for VZV IgM antibody detected high titers of virus-specific IgM in all patients with varicella and in 5 of 10 zoster patients. VZV IgM antibody was not detected in patients with primary herpes simplex virus infections or in other individuals without active VZV infection, with one exception, a patient with encephalitis who had other serological findings compatible with a reactivated VZV infection. VZV-specific IgA and IgG antibody titers demonstrable by ACCA were compared with those measured by solid-phase indirect enzyme immunofluorescence assay (EIFA). VZV IgA antibody titers detected in patients with varicella and zoster were variable and could not be considered to be reliable markers of active VZV infection. IgA antibody titers detected by ACCA tended to be higher than those demonstrated by solid-phase indirect EIFA in varicella and zoster patients. VZV IgG antibody titers detected by ACCA in patients with varicella, and to a lesser extent in zoster patients, were as high as or higher than those demonstrated by solid-phase indirect EIFA. However, ACCA was totally insensitive in detecting VZV IgG antibody in individuals with past infections with VZV and would not be a suitable approach for determination of immunity status to VZV. PMID:6330163

Keratitis in association with herpes zoster and varicella vaccines.

PubMed

Grillo, A P; Fraunfelder, F W

2017-07-01

The objective of this review was to collect reports of keratitis in association with herpes zoster virus (HZV) or varicella zoster virus (VZV) vaccines. HZV vaccination is intended for at-risk adult populations and VZV vaccination is intended for all pediatric patients. We reviewed the literature and reports of keratitis in association with herpes zoster or varicella vaccine from the National Registry of Drug-Induced Ocular Side Effects and the World Health Organization. Twenty-four cases of unilateral keratitis in association with VZV vaccines were collected from the adverse reaction databases and literature. In most cases, the onset of keratitis occurred within days of vaccination and resolved with topical steroid eye drops and oral acyclovir. Data suggest that keratitis in association with herpes zoster or varicella vaccine is rare, is usually self-limited or resolves with treatment. The mechanism may be the persistence of viral antigens in the cornea after VZV vaccination or herpes zoster ophthalmicus. This reaction is probable, given the plausible biological mechanism, the temporal relationship between vaccination and keratitis, and overall patterns of presentation after vaccination. Copyright 2017 Clarivate Analytics.

Full-Genome Sequence of a Novel Varicella-Zoster Virus Clade Isolated in Mexico.

PubMed

Garcés-Ayala, Fabiola; Rodríguez-Castillo, Araceli; Ortiz-Alcántara, Joanna María; Gonzalez-Durán, Elizabeth; Segura-Candelas, José Miguel; Pérez-Agüeros, Sandra Ivette; Escobar-Escamilla, Noé; Méndez-Tenorio, Alfonso; Diaz-Quiñonez, José Alberto; Ramirez-González, José Ernesto

2015-07-09

Varicella-zoster virus (VZV) is a member of the Herpesviridae family, which causes varicella (chicken pox) and herpes zoster (shingles) in humans. Here, we report the complete genome sequence of varicella-zoster virus, isolated from a vesicular fluid sample, revealing the circulation of VZV clade VIII in Mexico. Copyright © 2015 Garcés-Ayala et al.

Varicella and herpes zoster vaccine development: lessons learned.

PubMed

Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

2017-12-01

Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines' efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms.

Varicella and herpes zoster vaccine development: lessons learned

PubMed Central

Warren-Gash, Charlotte; Forbes, Harriet; Breuer, Judith

2017-01-01

ABSTRACT Introduction: Before vaccination, varicella zoster virus (VZV), which is endemic worldwide, led to almost universal infection. This neurotropic virus persists lifelong by establishing latency in sensory ganglia, where its reactivation is controlled by VZV-specific T-cell immunity. Lifetime risk of VZV reactivation (zoster) is around 30%. Vaccine development was galvanised by the economic and societal burden of VZV, including debilitating zoster complications that largely affect older individuals. Areas covered: We describe the story of development, licensing and implementation of live attenuated vaccines against varicella and zoster. We consider the complex backdrop of VZV virology, pathogenesis and immune responses in the absence of suitable animal models and examine the changing epidemiology of VZV disease. We review the vaccines’ efficacy, safety, effectiveness and coverage using evidence from trials, observational studies from large routine health datasets and clinical post-marketing surveillance studies and outline newer developments in subunit and inactivated vaccines. Expert commentary: Safe and effective, varicella and zoster vaccines have already made major inroads into reducing the burden of VZV disease globally. As these live vaccines have the potential to reactivate and cause clinical disease, developing alternatives that do not establish latency is an attractive prospect but will require better understanding of latency mechanisms. PMID:29047317

Definition and management of varicella zoster virus-associated meningoradiculitis: a case report.

PubMed

Luisier, Vincent; Weber, Lalensia; Fishman, Daniel; Praz, Gérard; Ghika, Joseph-André; Genoud, Didier; Chabwine, Joelle Nsimire

2016-09-26

The varicella zoster virus affects the central or peripheral nervous systems upon reactivation, especially when cell-mediated immunity is impaired. Among varicella zoster virus-related neurological syndromes, meningoradiculitis is an ill-defined condition for which clear management guidelines are still lacking. Zoster paresis is usually considered to be a varicella zoster virus-peripheral nervous system complication and treated with oral antiviral therapy. Yet in the literature, the few reported cases of herpes zoster with mild cerebral spinal fluid inflammation were all considered meningoradiculitis and treated using intravenous antiviral drugs, despite absence of systemic signs of meningitis. Nevertheless, these two clinical pictures are very similar. We report the case of an alcohol-dependent elderly Caucasian man presenting with left lower limb zoster paresis and mild cerebral spinal fluid inflammation, with favorable outcome upon IV antiviral treatment. We discuss interpretation of liquor inflammation in the absence of clinical meningitis and implications for the antiviral treatment route. From this case report we suggest that varicella zoster virus-associated meningoradiculitis should necessarily include meningitis symptoms with the peripheral neurological deficits and cerebral spinal fluid inflammation, requiring intravenous antiviral treatment. In the absence of (cell-mediated) immunosuppression, isolated zoster paresis does not necessitate spinal tap or intravenous antiviral therapy.

Varicella zoster meningitis complicating combined anti-tumor necrosis factor and corticosteroid therapy in Crohn's disease.

PubMed

Ma, Christopher; Walters, Brennan; Fedorak, Richard N

2013-06-07

Opportunistic viral infections are a well-recognized complication of anti-tumor necrosis factor (TNF) therapy for inflammatory bowel disease (IBD). Cases of severe or atypical varicella zoster virus infection, both primary and latent reactivation, have been described in association with immunosuppression of Crohn's disease (CD) patients. However, central nervous system varicella zoster virus infections have been rarely described, and there are no previous reports of varicella zoster virus meningitis associated with anti-TNF therapy among the CD population. Here, we present the case of a 40-year-old male with severe ileocecal-CD who developed a reactivation of dermatomal herpes zoster after treatment with prednisone and adalimumab. The reactivation presented as debilitating varicella zoster virus meningitis, which was not completely resolved despite aggressive antiviral therapy with prolonged intravenous acyclovir and subsequent oral valacyclovir. This is the first reported case of opportunistic central nervous system varicella zoster infection complicating anti-TNF therapy in the CD population. This paper also reviews the literature on varicella zoster virus infections of immunosuppressed IBD patients and the importance of vaccination prior to initiation of anti-TNF therapy.

Varicella zoster with erythema multiforme in a young girl: a rare association.

PubMed

Kishore, B Nanda; Ankadavar, Nandini S; Kamath, Ganesh H; Martis, Jacintha

2014-05-01

Erythema multiforme (EM) is an acute, self-limited, mucocutaneous disorder regarded as a hypersensitivity reaction which is triggered by various factors like infection, drugs, and food. Infectious agents are considered to be a major cause of EM other than idiopathic cause. A young girl presented with fluid-filled lesions all over the body of 3 days duration with history of similar lesions with fever in her sibling 2 weeks prior to admission. This was followed by large fluid-filled lesions with halo 3 days thereafter over the trunk, extremities suggesting target lesions of EM. The diagnosis was confirmed by cytology and positive serology. Varicella zoster virus (VZV) has rarely been reported as an etiological agent, despite its high incidence in childhood. VZV as an etiology of EM in a young girl has not been reported so far. This case was reported for its rare association of EM and varicella zoster and also for its rare presentation in a young girl.

Microbiology laboratory and the management of mother-child varicella-zoster virus infection

PubMed Central

De Paschale, Massimo; Clerici, Pierangelo

2016-01-01

Varicella-zoster virus, which is responsible for varicella (chickenpox) and herpes zoster (shingles), is ubiquitous and causes an acute infection among children, especially those aged less than six years. As 90% of adults have had varicella in childhood, it is unusual to encounter an infected pregnant woman but, if the disease does appear, it can lead to complications for both the mother and fetus or newborn. The major maternal complications include pneumonia, which can lead to death if not treated. If the virus passes to the fetus, congenital varicella syndrome, neonatal varicella (particularly serious if maternal rash appears in the days immediately before or after childbirth) or herpes zoster in the early years of life may occur depending on the time of infection. A Microbiology laboratory can help in the diagnosis and management of mother-child infection at four main times: (1) when a pregnant woman has been exposed to varicella or herpes zoster, a prompt search for specific antibodies can determine whether she is susceptible to, or protected against infection; (2) when a pregnant woman develops clinical symptoms consistent with varicella, the diagnosis is usually clinical, but a laboratory can be crucial if the symptoms are doubtful or otherwise unclear (atypical patterns in immunocompromised subjects, patients with post-vaccination varicella, or subjects who have received immunoglobulins), or if there is a need for a differential diagnosis between varicella and other types of dermatoses with vesicle formation; (3) when a prenatal diagnosis of uterine infection is required in order to detect cases of congenital varicella syndrome after the onset of varicella in the mother; and (4) when the baby is born and it is necessary to confirm a diagnosis of varicella (and its complications), make a differential diagnosis between varicella and other diseases with similar symptoms, or confirm a causal relationship between maternal varicella and malformations in a newborn

Pathogenesis and Current Approaches to Control of Varicella-Zoster Virus Infections

PubMed Central

Gershon, Michael D.

2013-01-01

SUMMARY Varicella-zoster virus (VZV) was once thought to be a fairly innocuous pathogen. That view is no longer tenable. The morbidity and mortality due to the primary and secondary diseases that VZV causes, varicella and herpes zoster (HZ), are significant. Fortunately, modern advances, including an available vaccine to prevent varicella, a therapeutic vaccine to diminish the incidence and ameliorate sequelae of HZ, effective antiviral drugs, a better understanding of VZV pathogenesis, and advances in diagnostic virology have made it possible to control VZV in the United States. Occult forms of VZV-induced disease have been recognized, including zoster sine herpete and enteric zoster, which have expanded the field. Future progress should include development of more effective vaccines to prevent HZ and a more complete understanding of the consequences of VZV latency in the enteric nervous system. PMID:24092852

Epidemic Varicella Zoster Virus among University Students, India.

PubMed

Meyers, Josh; Logaraj, Muthunarayanan; Ramraj, Balaji; Narasimhan, Padmanesan; MacIntyre, C Raina

2018-02-01

We investigated a yearlong varicella zoster virus outbreak in a highly susceptible young adult population at a large university in India. Outbreaks of varicella infection among adults are not well described in the literature. Infection control measures and vaccination policy for this age group and setting are needed.

The neurobiology of varicella zoster virus infection

PubMed Central

Gilden, D.; Mahalingam, R.; Nagel, M. A.; Pugazhenthi, S.; Cohrs, R. J.

2011-01-01

Varicella zoster virus (VZV) is a neurotropic herpesvirus that infects nearly all humans. Primary infection usually causes chickenpox (varicella), after which virus becomes latent in cranial nerve ganglia, dorsal root ganglia and autonomic ganglia along the entire neuraxis. Although VZV cannot be isolated from human ganglia, nucleic acid hybridization and, later, polymerase chain reaction proved that VZV is latent in ganglia. Declining VZV-specific host immunity decades after primary infection allows virus to reactivate spontaneously, resulting in shingles (zoster) characterized by pain and rash restricted to 1-3 dermatomes. Multiple other serious neurological and ocular disorders also result from VZV reactivation. This review summarizes the current state of knowledge of the clinical and pathological complications of neurological and ocular disease produced by VZV reactivation, molecular aspects of VZV latency, VZV virology and VZV-specific immunity, the role of apoptosis in VZV-induced cell death, and the development of an animal model provided by simian varicella virus infection of monkeys. PMID:21342215

Epidemic Varicella Zoster Virus among University Students, India

PubMed Central

Logaraj, Muthunarayanan; Ramraj, Balaji; Narasimhan, Padmanesan; MacIntyre, C. Raina

2018-01-01

We investigated a yearlong varicella zoster virus outbreak in a highly susceptible young adult population at a large university in India. Outbreaks of varicella infection among adults are not well described in the literature. Infection control measures and vaccination policy for this age group and setting are needed. PMID:29350152

[Neurological complications among patients with zoster hospitalized in Department of Infectious Diseases in Cracow in 2001-2006].

PubMed

Biesiada, Grazyna; Czepiel, Jacek; Sobczyk-Krupiarz, Iwona; Mach, Tomasz; Garlicki, Aleksander

2010-01-01

Herpes zoster is an infectious disease caused by varicella zoster virus (VZV). After replication at the place of entry, VZV spreads via the blood into the skin and mucosa, causing the varicella. From these regions VZV migrates into the sensory ganglia where it establishes a latent infection. The aim of our study was to analyze the localization of the skin changes and correlations of neurological complications among patient with zoster. We have reviewed medical documentation of the 67 patients with herpes zoster, hospitalized in our Department during the years 2001-2006. We have studied localization of the herpes zoster changes and frequency of neurological complications among these patients. Neuralgia was less intensive and last shorter time, when antiviral treatment had been started earlier. Neuralgia, meningitis, encephalitis and complications of the eye zoster were present more often among patients over 65 years old.

Childhood varicella-zoster virus vaccination in Belgium

PubMed Central

Bilcke, Joke; Jan van Hoek, Albert; Beutels, Philippe

2013-01-01

Aim: To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 years. Methods: An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster.  Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. Results and Conclusions: If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 years. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 years after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower. PMID:23321955

[Reactivation of herpes zoster infection by varicella-zoster virus].

PubMed

Cvjetković, D; Jovanović, J; Hrnjaković-Cvjetković, I; Brkić, S; Bogdanović, M

1999-01-01

There has been considerable interest in varicella-zoster virus in the middle of the twentieth century. Virus isolation in 1958 had made it possible to find out the complete DNA sequence of the varicella-zoster virus. Molecular identify of the causative agents of varicella and shingles had been proved. ETIOPATHOGENESIS AND HISTOPATHOLOGY: Varicella-zoster virus is a member of the Herpesviridae family. After primary infection which results in varicella, the virus becomes latent in the cerebral or posterior root ganglia. Some of these individuals develop shingles after several decades because of virus reactivation. It is caused by decline of cellular immune response. Circumstances such as old age, hard work, using of steroids or malignancies contribute to the appearance of shingles. Histopathological findings include degenerative changes of epithelial cells such as ballooning, multinucleated giant cells and eosinophilic intranuclear inclusions. Shingles occur sporadically, mainly among the elderly who have had varicella. There is no seasonal appearance of shingles. Individuals suffering from shingles may be sometimes contagious for susceptible children because of enormous amount of virus particles in vesicle fluid. Clinically, shingles is characterized at first by pain or discomfort in involved dermatome, usually without constitutional symptoms. Local edema and erythema appear before developing of rash. Maculopapular and vesicular rash evolves into crusts. The most commonly involved ganglia are: lumbar, thoracic, sacral posterior root ganglia, then geniculate ganglion of the VIIth cranial nerve and the trigeminal ganglion. The most common complication, postherpetic neuralgia, may last for as long as two or three weeks, sometimes even one year or more. Other complications that may be seen in shingles, but more rarely, are ocular (keratitis, iridocyclitis, secondary glaucoma, loss of sight), neurological (various motor neuropathies, encephalitis, Guillain-Barre syndrome

Clinical and molecular aspects of varicella zoster virus infection

PubMed Central

Gilden, Don; Nagel, Maria A.; Mahalingam, Ravi; Mueller, Niklaus H.; Brazeau, Elizabeth A.; Pugazhenthi, Subbiah; Cohrs, Randall J.

2009-01-01

Summary A declining cell-mediated immunity to varicella zoster virus (VZV) with advancing age or immunosuppression results in virus reactivation from latently infected human ganglia anywhere along the neuraxis. Virus reactivation produces zoster, often followed by chronic pain (postherpetic neuralgia or PHN) as well as vasculopathy, myelopathy, retinal necrosis and cerebellitis. VZV reactivation also produces pain without rash (zoster sine herpete). Vaccination after age 60 reduces the incidence of shingles by 51%, PHN by 66% and the burden of illness by 61%. However, even if every healthy adult over age 60 years is vaccinated, there would still be about 500,000 zoster cases annually in the United States alone, about 200,000 of whom will experience PHN. Analyses of viral nucleic acid and gene expression in latently infected human ganglia and in an animal model of varicella latency in primates are serving to determine the mechanism(s) of VZV reactivation with the aim of preventing reactivation and the clinical sequelae. PMID:19946620

Analysis of T Cell Responses during Active Varicella-Zoster Virus Reactivation in Human Ganglia

PubMed Central

Steain, Megan; Sutherland, Jeremy P.; Rodriguez, Michael; Cunningham, Anthony L.; Slobedman, Barry

2014-01-01

ABSTRACT Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had active herpes zoster. Ganglia innervating the site of the cutaneous herpes zoster rash showed evidence of necrosis, secondary to vasculitis, or localized hemorrhage. Despite this, there was limited evidence of VZV antigen expression, although a large inflammatory infiltrate was observed. Characterization of the infiltrating T cells showed a large number of infiltrating CD4+ T cells and cytolytic CD8+ T cells. Many of the infiltrating T cells were closely associated with neurons within the reactivated ganglia, yet there was little evidence of T cell-induced neuronal apoptosis. Notably, an upregulation in the expression of major histocompatibility complex class I (MHC-I) and MHC-II molecules was observed on satellite glial cells, implying these cells play an active role in directing the immune response during herpes zoster. This is the first detailed characterization of the interaction between T cells and neuronal cells within ganglia obtained from patients suffering herpes zoster at the time of death and provides evidence that CD4+ and cytolytic CD8+ T cell responses play an important role in controlling VZV replication in ganglia during active herpes zoster. IMPORTANCE VZV is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes a life-long dormant infection within the sensory ganglia and can reawaken to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. We examined ganglia obtained from individuals who, at the time of death, had

The cost-effectiveness of varicella and combined varicella and herpes zoster vaccination programmes in the United Kingdom.

PubMed

van Hoek, Albert Jan; Melegaro, Alessia; Gay, Nigel; Bilcke, Joke; Edmunds, W John

2012-02-01

Despite the existence of varicella vaccine, many developed countries have not introduced it into their national schedules, partly because of concerns about whether herpes zoster (HZ, shingles) will increase due to a lack of exogenous boosting. The magnitude of any increase in zoster that might occur is dependent on rates at which adults and children mix - something that has only recently been quantified - and could be reduced by simultaneously vaccinating older individuals against shingles. This study is the first to assess the cost-effectiveness of combined varicella and zoster vaccination options and compare this to alternative programmes. The cost-effectiveness of various options for the use of varicella-zoster virus (VZV) containing vaccines was explored using a transmission dynamic model. Underlying contact rates are estimated from a contemporary survey of social mixing patterns, and uncertainty in these derived from bootstrapping the original sample. The model was calibrated to UK data on varicella and zoster incidence. Other parameters were taken from the literature. UK guidance on perspective and discount rates were followed. The results of the incremental cost-effectiveness analysis suggest that a combined policy is cost-effective. However, the cost-effectiveness of this policy (and indeed the childhood two-dose policy) is influenced by projected benefits that accrue many decades (80-100 years or more) after the start of vaccination. If the programme is evaluated over shorter time frames, then it would be unlikely to be deemed cost-effective, and may result in declines in population health, due to a projected rise in the incidence of HZ. The findings are also sensitive to a number of parameters that are inaccurately quantified, such as the risk of HZ in varicella vaccine responders. Policy makers should be aware of the potential negative benefits in the first 30-50 years after introduction of a childhood varicella vaccine. This can only be partly mitigated

The burden of hospitalisation for varicella and herpes zoster in England from 2004 to 2013.

PubMed

Hobbelen, Peter H F; Stowe, Julia; Amirthalingam, Gayatri; Miller, Liz; van Hoek, Albert-Jan

2016-09-01

We aimed to determine the hospital burden of varicella-zoster virus infection (VZV) in England during 2004-2013 to support a future cost-effectiveness analysis of a childhood varicella vaccination programme. We analysed the incidence, duration, outcome and costs of hospitalisations for VZV using the Hospital Episode Statistics (HES) database for the general and immunocompetent population. Mortality in HES was validated using data from the Office for National Statistics (ONS). The average annual incidences of admissions due to varicella and herpes zoster were 7.6 (7.3-7.9) and 8.8 (8.6-9.0) per 100,000, respectively. The immunocompetent population accounted for 93% and 82% of the admissions due to varicella and herpes zoster, respectively. The average yearly number of hospital days was 10,748 (10,227-11,234) for varicella and 41,780 (40,257-43,287) for herpes zoster. The average yearly hospital costs (£2013/14) were £6.8 million (6.4-7.2) for varicella and £13.0 million (12.8-13.4) for herpes zoster. The average annual numbers of deaths identified in HES due to varicella and herpes zoster were 18.5 (14.3-22.8) and 160 (147-172), respectively. Comparison with ONS mortality data indicated a high level of uncertainty. Most of the hospital burden due to VZV-virus in England occurs in the immunocompetent population and is potentially vaccine-preventable. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Varicella zoster vaccines and their implications for development of HSV vaccines.

PubMed

Gershon, Anne A

2013-01-05

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinct pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV. Copyright © 2012 Elsevier Inc. All rights reserved.

Varicella zoster vaccines and their implications for development of HSV vaccines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gershon, Anne A., E-mail: aag1@columbia.edu

Live attenuated vaccines to prevent varicella and zoster have been available in the US for the past 17 years, with a resultant dramatic decrease in varicella incidence and a predicted future decrease in the incidence of zoster. The pathogenesis and immune responses to varicella zoster virus (VZV) as well as the safety and effectiveness of VZV vaccines are reviewed. The lack of sterilizing immunity provided by VZV vaccines has not prevented them from being safe and effective. Virological and pathological information concerning parallels and differences between VZV and herpes simplex virus (HSV) are highlighted. Although VZV and HSV are distinctmore » pathogens, they appear to have similarities in target organs and immunity that provide an expectation of a high likelihood for the success of vaccination against HSV, and predicted to be similar to that of VZV.« less

Risk of Herpes Zoster and Disseminated Varicella Zoster in Patients Taking Immunosuppressant Drugs at the Time of Zoster Vaccination.

PubMed

Cheetham, T Craig; Marcy, S Michael; Tseng, Hung-Fu; Sy, Lina S; Liu, In-Lu Amy; Bixler, Felicia; Baxter, Roger; Donahue, James G; Naleway, Allison L; Jacobsen, Steven J

2015-07-01

To determine the risks associated with zoster vaccine when administered to patients taking immunosuppressant medications. Patients enrolled in 1 of 7 managed care organizations affiliated with the Vaccine Safety Datalink between January 1, 2006, and December 31, 2009, were eligible. The exposure of interest was zoster vaccination in patients with current or remote immunosuppressant drug use. The primary outcomes were disseminated varicella zoster virus (VZV) and herpes zoster in the 42 days after vaccination. Automated data were collected on immunosuppressant drugs and baseline medical conditions. A logistic regression model using inverse probability treatment weights was used to estimate the odds of developing VZV or herpes zoster. A total of 14,554 individuals had an immunosuppressant medication dispensed around the time of vaccination, including 4826 with current use and 9728 with remote use. Most patients were taking low-dose corticosteroids. No cases of disseminated VZV were found in the current or remote users. The risk of herpes zoster was elevated in the 42 days after vaccination in current vs remote users (adjusted odds ratio, 2.99; 95% CI, 1.58-5.70). We found that patients taking immunosuppressant medications at the time of vaccination had a modest increased risk of herpes zoster in the 42 days after vaccination. The development of herpes zoster within 42 days after vaccination suggests that this is more likely due to reactivation of latent zoster virus than dissemination of the vaccine-derived varicella virus. These findings support the current zoster vaccination guidelines. Copyright © 2015 Mayo Foundation for Medical Education and Research. All rights reserved.

Cost-effectiveness of routine varicella vaccination using the measles, mumps, rubella and varicella vaccine in France: an economic analysis based on a dynamic transmission model for varicella and herpes zoster.

PubMed

Littlewood, Kavi J; Ouwens, Mario J N M; Sauboin, Christophe; Tehard, Bertrand; Alain, Sophie; Denis, François

2015-04-01

Each year in France, varicella and zoster affect large numbers of children and adults, resulting in medical visits, hospitalizations for varicella- and zoster-related complications, and societal costs. Disease prevention by varicella vaccination is feasible, wherein a plausible option involves replacing the combined measles, mumps, and rubella (MMR) vaccine with the combined MMR and varicella (MMRV) vaccine. This study aimed to: (1) assess the cost-effectiveness of adding routine varicella vaccination through MMRV, using different vaccination strategies in France; and (2) address key uncertainties, such as the economic consequences of breakthrough varicella cases, the waning of vaccine-conferred protection, vaccination coverage, and indirect costs. Based on the outputs of a dynamic transmission model that used data on epidemiology and costs from France, a cost-effectiveness model was built. A conservative approach was taken regarding the impact of varicella vaccination on zoster incidence by assuming the validity of the hypothesis of an age-specific boosting of immunity against varicella. The model determined that routine MMRV vaccination is expected to be a cost-effective option, considering a cost-effectiveness threshold of €20,000 per quality-adjusted life-year saved; routine vaccination was cost-saving from the societal perspective. Results were driven by a large decrease in varicella incidence despite a temporary initial increase in the number of zoster cases due to the assumption of exogenous boosting. In the scenario analyses, despite moderate changes in assumptions about incidence and costs, varicella vaccination remained a cost-effective option for France. Routine vaccination with MMRV was associated with high gains in quality-adjusted life-years, substantial reduction in the occurrences of varicella- and zoster-related complications, and few deaths due to varicella. Routine MMRV vaccination is also expected to provide reductions in costs related to

Recombination of Globally Circulating Varicella-Zoster Virus

PubMed Central

Depledge, Daniel P.; Kundu, Samit; Atkinson, Claire; Brown, Julianne; Haque, Tanzina; Hussaini, Yusuf; MacMahon, Eithne; Molyneaux, Pamela; Papaevangelou, Vassiliki; Sengupta, Nitu; Koay, Evelyn S. C.; Tang, Julian W.; Underhill, Gillian S.; Grahn, Anna; Studahl, Marie; Breuer, Judith; Bergström, Tomas

2015-01-01

ABSTRACT Varicella-zoster virus (VZV) is a human herpesvirus, which during primary infection typically causes varicella (chicken pox) and establishes lifelong latency in sensory and autonomic ganglia. Later in life, the virus may reactivate to cause herpes zoster (HZ; also known as shingles). To prevent these diseases, a live-attenuated heterogeneous vaccine preparation, vOka, is used routinely in many countries worldwide. Recent studies of another alphaherpesvirus, infectious laryngotracheitis virus, demonstrate that live-attenuated vaccine strains can recombine in vivo, creating virulent progeny. These findings raised concerns about using attenuated herpesvirus vaccines under conditions that favor recombination. To investigate whether VZV may undergo recombination, which is a prerequisite for VZV vaccination to create such conditions, we here analyzed 115 complete VZV genomes. Our results demonstrate that recombination occurs frequently for VZV. It thus seems that VZV is fully capable of recombination if given the opportunity, which may have important implications for continued VZV vaccination. Although no interclade vaccine-wild-type recombinant strains were found, intraclade recombinants were frequently detected in clade 2, which harbors the vaccine strains, suggesting that the vaccine strains have already been involved in recombination events, either in vivo or in vitro during passages in cell culture. Finally, previous partial and complete genomic studies have described strains that do not cluster phylogenetically to any of the five established clades. The additional VZV strains sequenced here, in combination with those previously published, have enabled us to formally define a novel sixth VZV clade. IMPORTANCE Although genetic recombination has been demonstrated to frequently occur for other human alphaherpesviruses, herpes simplex viruses 1 and 2, only a few ancient and isolated recent recombination events have hitherto been demonstrated for VZV. In the

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD.

PubMed

Naganuma, Makoto; Nagahori, Masakazu; Fujii, Toshimitsu; Morio, Junko; Saito, Eiko; Watanabe, Mamoru

2013-02-01

Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG < 10 IU/mL, anti-measles IgG < 16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy.

Protection From Varicella Zoster in Solid Organ Transplant Recipients Carrying Killer Cell Immunoglobulin-Like Receptor B Haplotypes.

PubMed

Schmied, Laurent; Terszowski, Grzegorz; Gonzalez, Asensio; Schmitter, Karin; Hirsch, Hans H; Garzoni, Christian; van Delden, Christian; Boggian, Katia; Mueller, Nicolas J; Berger, Christoph; Villard, Jean; Manuel, Oriol; Meylan, Pascal; Hess, Christoph; Stern, Martin

2015-12-01

Natural killer cell function is regulated by inhibitory and activating killer cell immunoglobulin-like receptors (KIR). Previous studies have documented associations of KIR genotype with the risk of cytomegalovirus (CMV) replication after solid organ transplantation. In this study of 649 solid organ transplant recipients, followed prospectively for infectious disease events within the Swiss Transplant Cohort Study, we were interested to see if KIR genotype associated with virus infections other than CMV. We found that KIR B haplotypes (which have previously been linked to protection from CMV replication) were associated with protection from varicella zoster virus infection (hazard ratio, 0.43; 95% confidence interval, 0.21-0.91; P = 0.03). No significant associations were detected regarding the risk of herpes simplex, Epstein-Barr virus or BK polyomavirus infections. In conclusion, these data provide evidence that the relative protection of KIR haplotype B from viral replication after solid organ transplantation may extend beyond CMV to other herpes viruses, such as varicella zoster virus and possibly Epstein-Barr virus.

Salivary Varicella Zoster Virus in Astronauts and in Patients of Herpes Zoster

NASA Technical Reports Server (NTRS)

Mehta, Satish; Pierson, Duane L.

2010-01-01

Spaceflight is a uniquely stressful environment with astronauts experiencing a variety of stressors including: isolation and confinement, psychosocial, noise, sleep deprivation, anxiety, variable gravitational forces, and increased radiation. These stressors are manifested through the HPA and SAM axes resulting in increased stress hormones. Diminished T-lymphocyte functions lead to reactivation of latent herpes viruses in astronauts during spaceflight. Herpes simplex virus reactivated with symptoms during spaceflight whereas Epstein-Barr virus (EBV), cytomegalovirus (CMV), and varicella zoster virus (VZV) reactivate and are shed without symptoms. EBV and VZV are shed in saliva and CMV in the urine. The levels of EBV shed in astronauts increased 10-fold during the flight; CMV and VZV are not typically shed in low stressed individuals, but both were shed in astronauts during spaceflight. All herpesviruses were detected by polymerase chain reaction (PCR) assay. Culturing revealed that VZV shed in saliva was infectious virus. The PCR technology was extended to test saliva of 54 shingles patients. All shingles patients shed VZV in their saliva, and the levels followed the course of the disease. Viremia was also found to be common during shingles. The technology may be used before zoster lesions appear allowing for prevention of disease. The technology may be used for rapid detection of VZV in doctors? offices. These studies demonstrated the value of applying technologies designed for astronauts to people on Earth.

The impact of 2-dose routine measles, mumps, rubella, and varicella vaccination in France on the epidemiology of varicella and zoster using a dynamic model with an empirical contact matrix.

PubMed

Ouwens, Mario J N M; Littlewood, Kavi J; Sauboin, Christophe; Téhard, Bertrand; Denis, François; Boëlle, Pierre-Yves; Alain, Sophie

2015-04-01

Varicella has a high incidence affecting the vast majority of the population in France and can lead to severe complications. Almost every individual infected by varicella becomes susceptible to herpes zoster later in life due to reactivation of the latent virus. Zoster is characterized by pain that can be long-lasting in some cases and has no satisfactory treatment. Routine varicella vaccination can prevent varicella. The vaccination strategy of replacing both doses of measles, mumps, and rubella (MMR) with a combined MMR and varicella (MMRV) vaccine is a means of reaching high vaccination coverage for varicella immunization. The objective of this analysis was to assess the impact of routine varicella vaccination, with MMRV in place of MMR, on the incidence of varicella and zoster diseases in France and to assess the impact of exogenous boosting of zoster incidence, age shift in varicella cases, and other possible indirect effects. A dynamic transmission population-based model was developed using epidemiological data for France to determine the force of infection, as well as an empirically derived contact matrix to reduce assumptions underlying these key drivers of dynamic models. Scenario analyses tested assumptions regarding exogenous boosting, vaccine waning, vaccination coverage, risk of complications, and contact matrices. The model provides a good estimate of the incidence before varicella vaccination implementation in France. When routine varicella vaccination is introduced with French current coverage levels, varicella incidence is predicted to decrease by 57%, and related complications are expected to decrease by 76% over time. After vaccination, it is observed that exogenous boosting is the main driver of change in zoster incidence. When exogenous boosting is assumed, there is a temporary increase in zoster incidence before it gradually decreases, whereas without exogenous boosting, varicella vaccination leads to a gradual decrease in zoster incidence

Clinical and biological differences between recurrent herpes simplex virus and varicella-zoster virus infections

DOE Office of Scientific and Technical Information (OSTI.GOV)

Straus, S.E.

1989-12-01

The major features that distinguish recurrent herpes simplex virus infections from zoster are illustrated in this article by two case histories. The clinical and epidemiologic features that characterize recurrent herpes simplex virus and varicella-zoster virus infections are reviewed. It is noted that herpesvirus infections are more common and severe in patients with cellular immune deficiency. Each virus evokes both humoral and cellular immune response in the course of primary infection. DNA hybridization studies with RNA probes labelled with sulfur-35 indicate that herpes simplex viruses persist within neurons, and that varicella-zoster virus is found in the satellite cells that encircle themore » neurons.« less

Bilateral Retrobulbar Optic Neuritis Caused by Varicella Zoster Virus in a Patient with AIDS

PubMed Central

Duda, Jose F.; Castro, Jose G.

2015-01-01

Aims To report on a case of bilateral retrobulbar optic neuritis in a patient with acquired immune deficiency syndrome (AIDS) caused by varicella-zoster virus (VZV); and to review the literature focusing on: cases reported, epidemiology, pathophysiology, diagnosis and treatment. Presentation of Case A 38-year-old woman with AIDS presented with a 10-day history of progressive bilateral visual loss and ocular pain. She had bilateral dilated pupils with no light perception; the fundoscopic examination was normal. Facial herpes zoster lesions appeared on the second day of hospitalization Magnetic resonance imaging (MRI) findings were compatible with a bilateral optic neuritis; the cerebrospinal fluid (CSF) showed pleocytosis, increased proteins and a positive VZV-DNA PCR. She was treated with intravenous acyclovir and corticosteroids and was able, when discharged 2 weeks after admission, to carry out activities of daily living. Discussion VZV retrobulbar optic neuritis has previously been reported in 12 patients with AIDS, more than half of the cases had concomitant herpes zoster and an associated retinopathy. A positive VZV-DNA in the CSF is indicative of VZV infection, initial use of intravenous acyclovir is recommended, and the concomitant use of corticosteroids would be a prudent choice; the duration of antiviral therapy remains undefined. Conclusion VZV retrobulbar optic neuritis in AIDS patients can occur with or without herpes zoster. It is a sight-threatening infectious and inflammatory process requiring the advice of specialists in infectious diseases, ophthalmology, neurology and viral microbiology. PMID:26740936

Zoster Vaccination Increases the Breadth of CD4+ T Cells Responsive to Varicella Zoster Virus

PubMed Central

Laing, Kerry J.; Russell, Ronnie M.; Dong, Lichun; Schmid, D. Scott; Stern, Michael; Magaret, Amalia; Haas, Jürgen G.; Johnston, Christine; Wald, Anna; Koelle, David M.

2015-01-01

Background. The live, attenuated varicella vaccine strain (vOka) is the only licensed therapeutic vaccine. Boost of varicella zoster virus (VZV)–specific cellular immunity is a likely mechanism of action. We examined memory CD4+ T-cell responses to each VZV protein at baseline and after zoster vaccination. Methods. Serial blood samples were collected from 12 subjects vaccinated with Zostavax and immunogenicity confirmed by ex vivo VZV-specific T-cell and antibody assays. CD4+ T-cell lines enriched for VZV specificity were generated and probed for proliferative responses to every VZV protein and selected peptide sets. Results. Zoster vaccination increased the median magnitude (2.3-fold) and breadth (4.2-fold) of VZV-specific CD4+ T cells one month post-vaccination. Both measures declined by 6 months. The most prevalent responses at baseline included VZV open reading frames (ORFs) 68, 4, 37, and 63. After vaccination, responses to ORFs 40, 67, 9, 59, 12, 62, and 18 were also prevalent. The immunogenicity of ORF9 and ORF18 were confirmed using peptides, defining a large number of discrete CD4 T-cell epitopes. Conclusions. The breadth and magnitude of the VZV-specific CD4+ T-cell response increase after zoster vaccination. In addition to glycoprotein E (ORF68), we identified antigenic ORFs that may be useful components of subunit vaccines. PMID:25784732

[Vaccines against varicella-zoster virus (VZV)].

PubMed

Salleras, Luis; Salleras, Montserrat; Soldevila, Nuria; Prat, Andreu; Garrido, Patricio; Domínguez, Ángela

2015-01-01

In Western countries, two attenuated varicella vaccines derived from the OKA strain are licensed: Varilrix® GlaxoSmithKline (OKA/RIT strain) and Varivax® Merck Sharp and Dohme (OKA/Merck strain). Currently, in Spain, varicella vaccination is only included in the Ministry of Health, Social Services and Equality official vaccination calendar for administration in adolescents who have not had the disease. Given the good results obtained in Navarra and Madrid with universal administration of the vaccine in children, it would be desirable to include the vaccine in the routine immunization schedule, with the administration of two doses at 15-18 months of age in the future. The protective efficacy of the attenuated herpes zoster vaccine was evaluated in the Shingles Prevention Study, which showed that in the short term (0-4 years) the vaccine reduced the incidence of herpes zoster by 53%, post-herpetic neuralgia by 66%, and the disease burden in immunocompetent persons aged ≥60 years by 61%. Another study demonstrated protective efficacy in persons aged 50-59 years. Over time, the protective efficacy decreases, but remains at acceptable levels, especially for post-herpetic neuralgia and the disease burden. Recently, the results of a controlled clinical trial (phase III) conducted in 18 countries to assess the protective efficacy of the inactivated subunit vaccine (glycoprotein E) adjuvanted with the adjuvant AS01B were published. The study inferred that the vaccine significantly reduced the incidence of herpes zoster in the short term (3.2 years) in people aged ≥50 years. Vaccine protection did not decrease with age at vaccination, ranging between 96.8% and 97.9% in all age groups. Copyright © 2015. Published by Elsevier España, S.L.U.

Sex differences underlying orofacial varicella zoster associated pain in rats.

PubMed

Stinson, Crystal; Deng, Mohong; Yee, Michael B; Bellinger, Larry L; Kinchington, Paul R; Kramer, Phillip R

2017-05-17

Most people are initially infected with varicella zoster virus (VZV) at a young age and this infection results in chickenpox. VZV then becomes latent and reactivates later in life resulting in herpes zoster (HZ) or "shingles". Often VZV infects neurons of the trigeminal ganglia to cause ocular problems, orofacial disease and occasionally a chronic pain condition termed post-herpetic neuralgia (PHN). To date, no model has been developed to study orofacial pain related to varicella zoster. Importantly, the incidence of zoster associated pain and PHN is known to be higher in women, although reasons for this sex difference remain unclear. Prior to this work, no animal model was available to study these sex-differences. Our goal was to develop an orofacial animal model for zoster associated pain which could be utilized to study the mechanisms contributing to this sex difference. To develop this model VZV was injected into the whisker pad of rats resulting in IE62 protein expression in the trigeminal ganglia; IE62 is an immediate early gene in the VZV replication program. Similar to PHN patients, rats showed retraction of neurites after VZV infection. Treatment of rats with gabapentin, an agent often used to combat PHN, ameliorated the pain response after whisker pad injection. Aversive behavior was significantly greater for up to 7 weeks in VZV injected rats over control inoculated rats. Sex differences were also seen such that ovariectomized and intact female rats given the lower dose of VZV showed a longer affective response than male rats. The phase of the estrous cycle also affected the aversive response suggesting a role for sex steroids in modulating VZV pain. These results suggest that this rat model can be utilized to study the mechanisms of 1) orofacial zoster associated pain and 2) the sex differences underlying zoster associated pain.

Varicella Seroprevalence and Molecular Epidemiology of Varicella-Zoster Virus in Argentina, 2002

PubMed Central

Dayan, Gustavo H.; Panero, María S.; Debbag, Roberto; Urquiza, Ana; Molina, Marta; Prieto, Susana; del Carmen Perego, María; Scagliotti, Graciela; Galimberti, Diana; Carroli, Guillermo; Wolff, Cristina; Schmid, D. Scott; Loparev, Vladimir; Guris, Dalya; Seward, Jane

2004-01-01

There is limited data on immunity against varicella-zoster virus (VZV) in adults in different parts of Argentina, and it is not known which VZV strains are circulating in Argentina. The objectives of this study were as follows: (i) to evaluate seroprevalence of varicella among adults, assessing the accuracy of clinical history and determining the sociodemographic factors associated with seropositivity; and (ii) to determine the VZV strains circulating in Argentina. A cross-sectional serological survey enrolling 2,807 women aged 15 to 49 years attending public health-care settings in four cities in Argentina (i.e., Buenos Aires, Salta, Mendoza, and Rosario) and one rural area was conducted from August to November 2002. Specimens for identification of VZV strains were obtained from vesicular lesions from 13 pediatric patients with varicella from different areas of the country. PCR amplification was used for genotyping. The overall seroprevalence of varicella antibodies was 98.5% (95% confidence interval, 98.0 to 98.9), ranging from 97.2% in central Buenos Aires to 99.3% in southern Buenos Aires and Salta. Varicella seroprevalence increased with age. Crowding and length of residence in the same place were associated with seropositivity. The positive predictive value of varicella history for immunity to varicella was 99.4%; however, the negative predictive value was 2.5%. The European genotype was identified in all viral specimens. In Argentina, seroprevalence in women more than 15 years old was high regardless of the area of residence. Negative or uncertain varicella history was not a good predictor of immunity. VZV genotype was stable in all areas of the country. PMID:15583301

Varicella Zoster Virus and Relapsing Remitting Multiple Sclerosis

PubMed Central

Sotelo, Julio; Corona, Teresa

2011-01-01

Multiple sclerosis (MS) is an immune-mediated disorder; however, little is known about the triggering factors of the abnormal immune response. Different viruses from the herpes family have been mentioned as potential participants. Here, we review the evidences that support the association of varicella zoster virus (VZV) with MS. Epidemiological studies from geographical areas, where incidence of MS has increased in recent decades, pointed out a high frequency of varicella and zoster in the clinical antecedents of MS patients, and also laboratory investigations have found large quantities of DNA from VZV in leucocytes and cerebrospinal fluid of MS patients restricted to the ephemeral period of MS relapse, followed by disappearance of the virus during remission. The above observations and the peculiar features of VZV, mainly characterized by its neurotropism and long periods of latency followed by viral reactivation, support the idea on the participation of VZV in the etiology of MS. However, as with reports from studies with other viruses, particularly Epstein Barr virus, conflicting results on confirmatory studies about the presence of viral gene products in brain tissue indicate the need for further research on the potential participation of VZV in the etiology of MS. PMID:22096629

A rapid radioimmunoassay using /sup 125/I-labeled staphylococcal protein A for antibody to varicella-zoster virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Richman, D.D.; Cleveland, P.H.; Oxman, M.N.

1981-05-01

A sensitive radioimmunoassay for serum antibody to varicella-zoster virus is described; it uses 125I-labeled staphylococcal protein A and a specially designed immunofiltration apparatus. The assay accurately distinguishes between individuals who are susceptible and those who are immune to infection with varicella-zoster virus. In addition, it can detect passive antibody in recipients of varicella-zoster immune globulin. This radioimmunoassay also detects the heterologous antibody responses that occasionally occur in patients infected with herpes simplex virus, which also have been detected by other antibody assays. The particular advantages of this assay are the use of noninfectious reagents, the speed of execution (less thanmore » 3 hr), the requirement for only small quantities of serum (30 microliters), the objectivity of end-point determination, and the capability of screening large numbers of sera. Consequently, this radioimmunoassay is especially useful for the rapid identification of susceptible individuals, which is essential for the appropriate management of patients and hospital personnel after exposure to varicella.« less

The role of solar ultraviolet irradiation in zoster.

PubMed Central

Zak-Prelich, M.; Borkowski, J. L.; Alexander, F.; Norval, M.

2002-01-01

Ultraviolet radiation (UVR) suppresses many aspects of cell-mediated immunity but it is uncertain whether solar UV exposure alters resistance to human infectious diseases. Varicella-zoster virus (VZV) causes varicella (chickenpox) and can reactivate from latency to cause zoster (shingles). The monthly incidence of chickenpox and zoster in a defined Polish population over 2 years was recorded and ground level solar UV was measured daily. There was a significant seasonality of UVR. Evidence of seasonal variation was found for all zoster cases and for zoster in males, with the lowest number of cases in the winter. The number of zoster cases with lesions occurring on exposed body sites (the face) demonstrated highly significant seasonality with a peak in July/August. Seasonal models for UVR and zoster cases showed similar temporal patterns. By contrast, for varicella, the maximum number of cases was found in March and the minimum in August/September, probably explained by the respiratory spread of VZV. It is tempting to speculate that the increase in solar UVR in the summer could induce suppression of cellular immunity, thus contributing to the corresponding rise in the incidence of zoster. PMID:12558343

The role of solar ultraviolet irradiation in zoster.

PubMed

Zak-Prelich, M; Borkowski, J L; Alexander, F; Norval, M

2002-12-01

Ultraviolet radiation (UVR) suppresses many aspects of cell-mediated immunity but it is uncertain whether solar UV exposure alters resistance to human infectious diseases. Varicella-zoster virus (VZV) causes varicella (chickenpox) and can reactivate from latency to cause zoster (shingles). The monthly incidence of chickenpox and zoster in a defined Polish population over 2 years was recorded and ground level solar UV was measured daily. There was a significant seasonality of UVR. Evidence of seasonal variation was found for all zoster cases and for zoster in males, with the lowest number of cases in the winter. The number of zoster cases with lesions occurring on exposed body sites (the face) demonstrated highly significant seasonality with a peak in July/August. Seasonal models for UVR and zoster cases showed similar temporal patterns. By contrast, for varicella, the maximum number of cases was found in March and the minimum in August/September, probably explained by the respiratory spread of VZV. It is tempting to speculate that the increase in solar UVR in the summer could induce suppression of cellular immunity, thus contributing to the corresponding rise in the incidence of zoster.

Herpes zoster - typical and atypical presentations.

PubMed

Dayan, Roy Rafael; Peleg, Roni

2017-08-01

Varicella- zoster virus infection is an intriguing medical entity that involves many medical specialties including infectious diseases, immunology, dermatology, and neurology. It can affect patients from early childhood to old age. Its treatment requires expertise in pain management and psychological support. While varicella is caused by acute viremia, herpes zoster occurs after the dormant viral infection, involving the cranial nerve or sensory root ganglia, is re-activated and spreads orthodromically from the ganglion, via the sensory nerve root, to the innervated target tissue (skin, cornea, auditory canal, etc.). Typically, a single dermatome is involved, although two or three adjacent dermatomes may be affected. The lesions usually do not cross the midline. Herpes zoster can also present with unique or atypical clinical manifestations, such as glioma, zoster sine herpete and bilateral herpes zoster, which can be a challenging diagnosis even for experienced physicians. We discuss the epidemiology, pathophysiology, diagnosis and management of Herpes Zoster, typical and atypical presentations.

[Modelling the impact of vaccination on the epidemiology of varicella zoster virus].

PubMed

Bonmarin, I; Santa-Olalla, P; Lévy-Bruhl, D

2008-10-01

The soon to come the availability of a combined MMR-varicella vaccine has re-stimulated the debate around universal infant vaccination against varicella. In France, the incidence of varicella is estimated at about 700,000 cases per year, with approximately 3500 hospitalisations and 15-25 deaths, the latter mainly occurring in those over 15years. Vaccination would certainly decrease the overall incidence of the disease but concerns about vaccination leading to a shift in the average age at infection followed by an increase in incidence of severe cases and congenital varicella, still remain. In order to provide support for decision-making, a dynamic mathematical model of varicella virus transmission was used to predict the effect of different vaccination strategies and coverages on the epidemiology of varicella and zoster. A deterministic realistic age-structured model was adapted to the French situation. Epidemiological parameters were estimated from literature or surveillance data. Various vaccine coverages and vaccination strategies were investigated. A sensitivity analysis of varicella incidence predictions was performed to test the impact of changes in the vaccine parameters and age-specific mixing patterns. The model confirms that the overall incidence and morbidity of varicella would likely be reduced by mass vaccination of 12-month-old children. Whatever the coverage and the vaccine strategy, the vaccination will cause a shift in age distribution with, for vaccination coverage up to at least 80% in the base-case analysis, an increased morbidity among adults and pregnant women. However, the total number of deaths and hospitalisations from varicella is predicted to remain below that expected without vaccination. The model is very sensitive to the matrix of contacts used and to the parameters describing vaccine effectiveness. Zoster incidence will increase over a number of decades followed by a decline to below prevaccination levels. Mass varicella vaccination

Varicella zoster virus latency

PubMed Central

Eshleman, Emily; Shahzad, Aamir; Cohrs, Randall J

2011-01-01

Primary infection by varicella zoster virus (VZV) typically results in childhood chickenpox, at which time latency is established in the neurons of the cranial nerve, dorsal root and autonomic ganglia along the entire neuraxis. During latency, the histone-associated virus genome assumes a circular episomal configuration from which transcription is epigenetically regulated. The lack of an animal model in which VZV latency and reactivation can be studied, along with the difficulty in obtaining high-titer cell-free virus, has limited much of our understanding of VZV latency to descriptive studies of ganglia removed at autopsy and analogy to HSV-1, the prototype alphaherpesvirus. However, the lack of miRNA, detectable latency-associated transcript and T-cell surveillance during VZV latency highlight basic differences between the two neurotropic herpesviruses. This article focuses on VZV latency: establishment, maintenance and reactivation. Comparisons are made with HSV-1, with specific attention to differences that make these viruses unique human pathogens. PMID:21695042

Distribution of Health Effects and Cost-effectiveness of Varicella Vaccination are Shaped by the Impact on Herpes Zoster.

PubMed

van Lier, Alies; Lugnér, Anna; Opstelten, Wim; Jochemsen, Petra; Wallinga, Jacco; Schellevis, François; Sanders, Elisabeth; de Melker, Hester; van Boven, Michiel

2015-10-01

Varicella zoster virus (VZV) is the etiological agent of varicella and herpes zoster (HZ). It has been hypothesised that immune boosting of latently infected persons by contact with varicella reduces the probability of HZ. If true, universal varicella vaccination may increase HZ incidence due to reduced VZV circulation. To inform decision-making, we conduct cost-effectiveness analyses of varicella vaccination, including effects on HZ. Effects of varicella vaccination are simulated with a dynamic transmission model, parameterised with Dutch VZV seroprevalence and HZ incidence data, and linked to an economic model. We consider vaccination scenarios that differ by whether or not they include immune boosting, and reactivation of vaccine virus. Varicella incidence decreases after introduction of vaccination, while HZ incidence may increase or decrease depending on whether or not immune boosting is present. Without immune boosting, vaccination is expected to be cost-effective or even cost-saving. With immune boosting, vaccination at 95% coverage is not expected to be cost-effective, and may even cause net health losses. Cost-effectiveness of varicella vaccination depends strongly on the impact on HZ and the economic time horizon. Our findings reveal ethical dilemmas as varicella vaccination may result in unequal distribution of health effects between generations.

Varicella-Zoster Virus in Perth, Western Australia: Seasonality and Reactivation.

PubMed

Korostil, Igor A; Regan, David G

2016-01-01

Identification of the factors affecting reactivation of varicella-zoster virus (VZV) largely remains an open question. Exposure to solar ultra violet (UV) radiation is speculated to facilitate reactivation. Should the role of UV in reactivation be significant, VZV reactivation patterns would generally be expected to be synchronous with seasonal UV profiles in temperate climates. We analysed age and gender specific VZV notification time series data from Perth, Western Australia (WA). This city has more daily sunshine hours than any other major Australian city. Using the cosinor and generalized linear models, we tested these data for seasonality and correlation with UV and temperature. We established significant seasonality of varicella notifications and showed that while herpes-zoster (HZ) was not seasonal it had a more stable seasonal component in males over 60 than in any other subpopulation tested. We also detected significant association between HZ notifications and UV for the entire Perth population as well as for females and males separately. In most cases, temperature proved to be a significant factor as well. Our findings suggest that UV radiation may be important for VZV reactivation, under the assumption that notification data represent an acceptably accurate qualitative measure of true VZV incidence.

Latency of Varicella Zoster Virus in Dorsal Root, Cranial, and Enteric Ganglia in Vaccinated Children

PubMed Central

Gershon, Anne A.; Chen, Jason; Davis, Larry; Krinsky, Clarissa; Cowles, Robert; Reichard, Ross; Gershon, Michael

2012-01-01

Despite vaccination, varicella-zoster virus (VZV) remains an important pathogen. We investigated VZV latency in autopsy specimens from vaccinees, in gastrointestinal tissue removed surgically, and in a guinea pig model. We propose that retrograde transport from infected skin and viremia deliver VZV to neurons in which it becomes latent. Wild type (WT) VZV was found to be latent in many ganglia of vaccinated children with no history of varicella, suggesting that subclinical infection with WT-VZV occurs with subsequent viremic dissemination. The 30% to 40% rate of WT-VZV zoster reported in vaccinees and occasional trigeminal zoster due to vaccine type VZV (vOka) are consistent with viremic delivery of VZV to multiple ganglia. Most human intestinal specimens contained latent VZV within neurons of the enteric nervous system (ENS). Induction of viremia in guinea pigs led to VZV latency throughout the ENS. The possibility VZV reactivation in the ENS is an unsuspected cause of gastrointestinal disease requires future investigation. PMID:23303966

Association of progressive outer retinal necrosis and varicella zoster encephalitis in a patient with AIDS.

PubMed Central

van den Horn, G J; Meenken, C; Troost, D

1996-01-01

BACKGROUND: A patient with AIDS who developed the clinical picture of bilateral progressive outer retinal necrosis (PORN) in combination with varicella zoster encephalitis is described. The picture developed more than 2 years after an episode of ophthalmic zoster infection, and following intermittent exposure to oral acyclovir because of recurrent episodes of cutaneous herpes simplex infection. METHODS: Aqueous humour, obtained by paracentesis of the anterior chamber, was analysed using immunofluorescence and polymerase chain reaction (PCR). Postmortem analysis of eye and brain tissue was performed by using conventional techniques and in situ hybridisation. RESULTS: While conventional techniques all failed to detect a causative agent, analysis of the aqueous humour using PCR, and histological examination of necropsy specimens from eyes and brain using in situ hybridisation were conclusive for the diagnosis varicella zoster virus (VZV) infection. CONCLUSION: This case documents the presumed association of PORN and VZV encephalitis in a severely immunocompromised AIDS patient. Images PMID:8976726

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model of Persistent Varicella-Zoster Virus Infection

PubMed Central

Goodwin, Thomas J.; McCarthy, Maureen; Osterrieder, Nikolaus; Cohrs, Randall J.; Kaufer, Benedikt B.

2013-01-01

Varicella-zoster virus (VZV) is a neurotropic human alphaherpesvirus that causes varicella upon primary infection, establishes latency in multiple ganglionic neurons, and can reactivate to cause zoster. Live attenuated VZV vaccines are available; however, they can also establish latent infections and reactivate. Studies of VZV latency have been limited to the analyses of human ganglia removed at autopsy, as the virus is strictly a human pathogen. Recently, terminally differentiated human neurons have received much attention as a means to study the interaction between VZV and human neurons; however, the short life-span of these cells in culture has limited their application. Herein, we describe the construction of a model of normal human neural progenitor cells (NHNP) in tissue-like assemblies (TLAs), which can be successfully maintained for at least 180 days in three-dimensional (3D) culture, and exhibit an expression profile similar to that of human trigeminal ganglia. Infection of NHNP TLAs with cell-free VZV resulted in a persistent infection that was maintained for three months, during which the virus genome remained stable. Immediate-early, early and late VZV genes were transcribed, and low-levels of infectious VZV were recurrently detected in the culture supernatant. Our data suggest that NHNP TLAs are an effective system to investigate long-term interactions of VZV with complex assemblies of human neuronal cells. PMID:23935496

Clinical course and therapeutic approach to varicella zoster virus infection in children with rheumatic autoimmune diseases under immunosuppression.

PubMed

Leuvenink, Raphael; Aeschlimann, Florence; Baer, Walter; Berthet, Gerald; Cannizzaro, Elvira; Hofer, Michael; Kaiser, Daniela; Schroeder, Silke; Heininger, Ulrich; Woerner, Andreas

2016-06-02

To analyze the clinical presentation and complications of varicella zoster virus (VZV) infection in children with rheumatic diseases treated with immunosuppressive medication such as biological disease-modifying antirheumatic drugs (bDMARDs) and/or conventional disease-modifying antirheumatic drugs (cDMARDs), and to analyze the therapeutic approach to VZV infections with respect to the concomitant immunosuppressive treatment. Retrospective multicenter study using the Swiss Pediatric Rheumatology registry. Children with rheumatic diseases followed in a Swiss center for pediatric rheumatology and treated with cDMARD and/or bDMARD with a clinical diagnosis of varicella or herpes zoster between January 2004 and December 2013 were included. Twenty-two patients were identified, of whom 20 were treated for juvenile idiopathic arthritis, 1 for a polyglandular autoimmune syndrome type III, and 1 for uveitis. Of these 22 patients, 16 had varicella and 6 had herpes zoster. Median age at VZV disease was 7.6 years (range 2 to 17 years), with 6.3 years (range 2 to 17 years) for those with varicella and 11.6 years (range 5 to 16 years) for those with herpes zoster. The median interval between start of immunosuppression and VZV disease was 14.1 months (range 1 to 63 months). Two patients had received varicella vaccine (1 dose each) prior to start of immunosuppression. Concomitant immunosuppressive therapy was methotrexate (MTX) monotherapy (n = 9) or bDMARD monotherapy (n = 2), or a combination of bDMARD with prednisone, MTX or Leflunomide (n = 11). Four patients experienced VZV related complications: cellulitis in 1 patient treated with MTX, and cellulitis, sepsis and cerebellitis in 3 patients treated with biological agents and MTX combination therapy. Six children were admitted to hospital (range of duration: 4 to 9 days) and 12 were treated with valaciclovir or aciclovir. The clinical course of varicella and herpes zoster in children under

Incidence of herpes zoster and seroprevalence of varicella-zoster virus in young adults of South Korea.

PubMed

Kang, Cheol-In; Choi, Chang-Min; Park, Tae-Sung; Lee, Dong-Jun; Oh, Myoung-don; Choe, Kang-Won

2008-05-01

This study was performed to determine the incidence of herpes zoster and seroprevalence of varicella-zoster virus (VZV) in young adults of South Korea, where VZV seroprevalence remains relatively high. In South Korea, military service is compulsory for all healthy young men and hence those in military service might provide a reflection of the general population. The computerized database of the Armed Forces Medical Command was examined to identify the number of reported herpes zoster cases. In order to evaluate VZV seroprevalence, serum samples were obtained from randomly selected subjects among those who had been admitted to the Armed Forces Capital Hospital. A total of 705 cases of herpes zoster were reported between June 2004 and May 2005. The annual incidence rate of herpes zoster was 141 (95% CI 131.0-151.8) per 100000 population. A total of 192 subjects were enrolled for the analysis of VZV seroprevalence. All subjects were male and their median age was 21 (range 19-24) years. The overall anti-VZV IgG seropositivity prevalence was 92.7% (178/192, 95% CI 88.0-95.7%). We have described a population-based study of the epidemiology of VZV infections in the military personnel of South Korea.

Current and future effects of varicella and herpes zoster vaccination in Germany - Insights from a mathematical model in a country with universal varicella vaccination.

PubMed

Horn, Johannes; Karch, André; Damm, Oliver; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Hengel, Hartmut; Greiner, Wolfgang; Mikolajczyk, Rafael T

2016-07-02

Varicella zoster virus (VZV) is primarily known for causing varicella in childhood, but can reactivate again as herpes zoster (HZ) after a period of latency, mainly in persons older than 50 years. Universal varicella vaccination was introduced in Germany in 2004, while HZ vaccination has not been recommended yet. We aimed to quantify the potential long-term effects of universal childhood varicella vaccination and HZ vaccination of the elderly on varicella and HZ incidence in Germany over a time horizon of 100 years, using a transmission model calibrated to pre-vaccination data and validated against early post-vaccination data. Using current vaccination coverage rates of 87% (64%) with one (two) varicella vaccine dose(s), the model predicts a decrease in varicella cases by 89% for the year 2015. In the long run, the incidence reduction will stabilize at about 70%. Under the assumption of the boosting hypothesis of improved HZ protection caused by exposure to VZV, the model predicts a temporary increase in HZ incidence of up to 20% for around 50 years. HZ vaccination of the elderly with an assumed coverage of 20% has only limited effects in counteracting this temporary increase in HZ incidence. However, HZ incidence is shown to decrease in the long-term by 58% as vaccinated individuals get older and finally reach age-classes with originally high HZ incidence. Despite substantial uncertainties around several key variables, the model's results provide valuable insights that support decision-making regarding national VZV vaccination strategies.

Varicella-Zoster Virus–Specific Immune Responses to Herpes Zoster in Elderly Participants in a Trial of a Clinically Effective Zoster Vaccine

PubMed Central

Zhang, Jane H.; Oxman, Michael N.; Johnson, Gary R.; Hayward, Anthony R.; Caulfield, Michael J.; Irwin, Michael R.; Clair, James; Smith, Jeffrey G.; Stanley, Harold; Marchese, Rocio D.; Harbecke, Ruth; Williams, Heather M.; Chan, Ivan S. F.; Arbeit, Robert D.; Gershon, Anne A.; Schödel, Florian; Morrison, Vicki A.; Kauffman, Carol A.; Straus, Steve E.; Schmader, Kenneth E.; Davis, Larry E.; Levin, Myron J.

2009-01-01

BackgroundThe objectives of this study were to evaluate the association between varicella-zoster virus (VZV)–specific humoral and cell-mediated immunity (CMI) to herpes zoster (HZ) and protection against HZ morbidity and to compare immune responses to HZ and zoster vaccine MethodsIn 981 elderly persons who developed HZ during a zoster vaccine efficacy trial (321 vaccinees and 660 placebo recipients) and 1362 without HZ (682 vaccinees and 680 placebo recipients), CMI was measured by VZV responder cell frequency and interferon-γ enzyme-linked immunospot, and antibodies were measured by VZV enzyme-linked immunosorbent assay against affinity-purified VZV glycoproteins (gpELISA) ResultsRobust VZV CMI at HZ onset correlated with reduced HZ morbidity, whereas VZV gpELISA titers did not. Three weeks after HZ onset, gpELISA titers were highest in those with more severe HZ and were slightly increased in placebo recipients (compared with zoster vaccine recipients) and in older individuals. VZV CMI responses to HZ were similar in zoster vaccine and placebo recipients and were not affected by demographic characteristics or antiviral therapy, except for responder cell frequency at HZ onset, which decreased with age. When responses to zoster vaccine and HZ could be compared, VZV CMI values were similar, but antibody titers were lower ConclusionsHigher VZV CMI at HZ onset was associated with reduced HZ severity and less postherpetic neuralgia. Higher antibody titers were associated with increased HZ severity and occurrence of postherpetic neuralgia. HZ and zoster vaccine generated comparable VZV CMI PMID:19712037

Investigation of varicella-zoster virus infection of lymphocytes by in situ hybridization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Koropchak, C.M.; Solem, S.M.; Diaz, P.S.

1989-05-01

Peripheral blood mononuclear cells harboring viral gene sequences were detected during primary varicella-zoster virus (VZV) infection of the human host and the strain 2 guinea pig by in situ hybridization with a /sup 3/H-labeled VZV DNA probe. Activated T lymphocytes were permissive for VZV infection at low frequency in vitro.

Varicella-Zoster Virus in Perth, Western Australia: Seasonality and Reactivation

PubMed Central

Korostil, Igor A.; Regan, David G.

2016-01-01

Background Identification of the factors affecting reactivation of varicella-zoster virus (VZV) largely remains an open question. Exposure to solar ultra violet (UV) radiation is speculated to facilitate reactivation. Should the role of UV in reactivation be significant, VZV reactivation patterns would generally be expected to be synchronous with seasonal UV profiles in temperate climates. Methods We analysed age and gender specific VZV notification time series data from Perth, Western Australia (WA). This city has more daily sunshine hours than any other major Australian city. Using the cosinor and generalized linear models, we tested these data for seasonality and correlation with UV and temperature. Results We established significant seasonality of varicella notifications and showed that while herpes-zoster (HZ) was not seasonal it had a more stable seasonal component in males over 60 than in any other subpopulation tested. We also detected significant association between HZ notifications and UV for the entire Perth population as well as for females and males separately. In most cases, temperature proved to be a significant factor as well. Conclusions Our findings suggest that UV radiation may be important for VZV reactivation, under the assumption that notification data represent an acceptably accurate qualitative measure of true VZV incidence. PMID:26963841

Immune response and reactogenicity of intradermal administration versus subcutaneous administration of varicella-zoster virus vaccine: an exploratory, randomised, partly blinded trial.

PubMed

Beals, Chan R; Railkar, Radha A; Schaeffer, Andrea K; Levin, Yotam; Kochba, Efrat; Meyer, Brian K; Evans, Robert K; Sheldon, Eric A; Lasseter, Kenneth; Lang, Nancy; Weinberg, Adriana; Canniff, Jennifer; Levin, Myron J

2016-08-01

The licensed live, attenuated varicella-zoster virus vaccine prevents herpes zoster in adults older than 50 years. We aimed to determine whether intradermal administration of zoster vaccine could enhance vaccine immunogenicity compared with conventional needle subcutaneous administration. In this randomised, dose-ranging study, adults aged 50 years or older who had a history of varicella or who had resided in a country with endemic varicella-zoster virus infection for 30 years or more were eligible. Participants received the approved full or a 1/3 dose of zoster vaccine given subcutaneously or one of four intradermal doses (full, 1/3, 1/10, or 1/27 dose) using the MicronJet600 device. The two subcutaneous doses and the four intradermal doses were randomised (1·5:1:1:1:1:1) by computer generated sequence with randomisation stratified by age (50-59 years or 60 years or older). The primary immunogenicity endpoint was the change from baseline in IgG antibody to varicella-zoster virus-specific glycoproteins (gpELISA) measured at 6 weeks. All patients were included in the primary and safety analyses. This study is registered with ClinicalTrials.gov, number NCT01385566. Between Sept 2, 2011, and Jan 13, 2012, 224 participants were enrolled from three clinics in the USA and 223 were randomly assigned: 52 to receive the full dose subcutaneous zoster vaccine, 34 to receive the 1/3 dose subcutaneous zoster vaccine, 34 to receive the full dose intradermal zoster vaccine, 35 to receive the 1/3 dose intradermal zoster vaccine, 34 to receive the 1/10 dose intradermal zoster vaccine, and 34 to receive the 1/27 dose intradermal zoster vaccine. Full dose zoster vaccine given subcutaneously resulted in a gpELISA geometric mean fold-rise (GMFR) of 1·74 (90% CI 1·48-2·04) at 6 weeks post-vaccination compared with intradermal administration which resulted in a significantly higher gpELISA GMFR of 3·25 (2·68-3·94; p<0·0001), which also remained high at 18 months. An apparent dose

Validity of medical record documented varicella-zoster virus among unvaccinated cohorts

PubMed Central

Mohanty, Salini; Perella, Dana; Jumaan, Aisha; Robinson, Donovan; Forke, Christine M; Schmid, D Scott; Renwick, Mia; Mankodi, Foram; Watson, Barbara; Fiks, Alexander G

2013-01-01

Background: A varicella diagnosis or verification of disease history by any healthcare provider is currently accepted for determining evidence of immunity by the Advisory Committee on Immunization Practices (ACIP). Objective: To examine the accuracy of medical record (MR) documented varicella history as a measure of varicella-zoster virus (VZV) immunity among unvaccinated individuals born after 1980. We also assessed methods to practically implement ACIP guidelines to verify varicella history using medical records. Study Design: As part of a larger cross-sectional study conducted at three Philadelphia clinics from 2004–2006, we recruited 536 unvaccinated patients aged 5–19 y (birth years: 1985–2001). Varicella history was obtained from three sources: parent/patient interview, any MR documentation (sick and well visits) and MR documentation of a sick visit for varicella. All participants were tested for VZV IgG. For each source and three age groups (5–9, 10–14, 15–19 y old), positive predictive value (PPV) was calculated. Specificity of varicella history was compared between different sources using McNemar’s Chi-square. Results: Among participants aged 5–9, 10–14 and 15–19 y the PPV for any MR documentation and sick visit diagnosis were 96% and 100%, 92% and 97%, and 99% and 100%, respectively. The specificity for sick visit documentation was higher than any MR documentation and patient/parent recall among all age groups; however, these differences were only statistically significant when comparing sick visit documentation to parent/patient recall for 10-14 y olds. Conclusion: Sick visit documentation of varicella in the MR is an accurate predictor of varicella seropositivity and useful for confirming disease history among unvaccinated persons (birth years: 1985–2001). This method is a practical way to verify varicella history using the ACIP guidelines. PMID:23807363

Nosocomial Varicella

PubMed Central

Meyers, Joel D.; MacQuarrie, Michael B.; Merigan, Thomas C.; Jennison, M. Harry

1979-01-01

Twenty cases of varicella occurred in patients or siblings of patients in a 41-day period in a children's hospital. Most cases were among oncology patients, with transmission occurring in both the inpatient and outpatient areas. One patient died after visceral dissemination of varicella. Neither pooled immunoglobulin nor zoster immune plasma was effective in preventing clinical varicella, although zoster immune plasma appeared to ameliorate the illness. Recommended control measures included strict isolation or discharge of infected patients, and respiratory isolation or discharge of exposed susceptibles. Although apparently too late to be effective in this outbreak, similar measures are warranted should nosocomial outbreaks of varicella occur elsewhere. PMID:425501

Vaccination to prevent varicella and shingles

PubMed Central

Breuer, J

2001-01-01

Vaccination of healthy children against varicella using the live attenuated Oka vaccine has been available in Japan and south Korea for several years. In 1996, a programme of universal vaccination of children to prevent varicella was introduced in the USA and other countries, including Canada, Germany, and Sweden, have licensed the vaccine for use in healthy children. This article reviews the origin of the Oka vaccine and the evidence for vaccine safety and efficacy in children and adults. Universal vaccination of children and targeted vaccination of groups at risk of severe varicella are discussed. The possible use of the Oka vaccine to prevent zoster is reviewed, and initiatives to develop new varicella zoster virus vaccines are outlined. Key Words: chickenpox • varicella zoster • herpes zoster • vaccination • leukaemia PMID:11577118

Varicella Zoster Virus in Saliva of Patients With Herpes Zoster

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Tyring, Stephen K.; Gilden, Donald H.; Cohrs, Randall J.; Leal, Melanie J.; Castro, Victoria A.; Feiveson, Alan H.; Ott, C. Mark; Pierson, Duane L.

2007-01-01

Background. VZV DNA is present in saliva of healthy astronauts and patients with Ramsay Hunt syndrome (geniculate zoster). We hypothesized that a prospective analysis of patients with zoster would detect VZV in saliva independent of zoster location. Methods. We treated 54 patients with valacyclovir. On the first treatment day, 7- and 14-days later, pain was scored and saliva examined for VZV DNA. Saliva from six subjects with chronic pain and 14 healthy subjects was similarly studied. Results. Follow-up data was available for 50/54 patients. Pain decreased in 43/50 (86 percent), disappeared in 37 (74 percent), recurred after disappearing in three (6 percent) and increased in four (8 percent). VZV DNA was found in every patient the day treatment was started, decreased in 47/50 (94 percent), transiently increased in three (6 percent) before decreasing, increased in two (4 percent) and disappeared in 41 (82 percent). There was a positive correlation between the presence of VZV DNA and pain, as well as between the VZV DNA copy number and pain (P<0.0005). Saliva of two patients was cultured, and infectious VZV was isolated from one. VZV DNA was present in one patient before rash and in four patients after pain resolved, and not in any control subjects. Conclusion. VZV DNA is present in saliva of zoster patients.

Rapid Detection of the Varicella Zoster Virus in Saliva

NASA Technical Reports Server (NTRS)

Pierson, Duane L.; Mehta, Satish K.; Cohrs, Randall J.; Gilden, Don H.; Harding, Robert E.

2011-01-01

Varicella zoster virus (VZV) causes chicken pox on first exposure (usually in children), and reactivates from latency causing shingles (usually in adults). Shingles can be extremely painful, causing nerve damage, organ damage, and blindness in some cases. The virus can be life-threatening in immune-compromised individuals. The virus is very difficult to culture for diagnosis, requiring a week or longer. This invention is a rapid test for VZV from a saliva sample and can be performed in a doctor s office. The kit is small, compact, and lightweight. Detec tion is sensitive, specific, and noninvasive (no needles); only a saliva sample is required. The test provides results in minutes. The entire test is performed in a closed system, with no exposure to infectious materials. The components are made mostly of inexpensive plastic injection molded parts, many of which can be purchased off the shelf and merely assembled. All biological waste is contained for fast, efficient disposal. This innovation was made possible because of discovery of a NASA scientists flight experiment showing the presence of VZV in saliva during high stress periods and disease. This finding enables clinicians to quickly screen patients for VZV and treat the ones that show positive results with antiviral medicines. This promotes a rapid recovery, easing of pain and symptoms, and reduces chances of complications from zoster. Screening of high-risk patients could be incorporated as part of a regular physical exam. These patients include the elderly, pregnant women, and immune-compromised individuals. In these patients, VZV can be a life-threatening disease. In both high- and low-risk patients, early detection and treatment with antiviral drugs can dramatically decrease or even eliminate the clinical manifestation of disease.

Varicella zoster virus-associated morbidity and mortality in Africa - a systematic review.

PubMed

Hussey, Hannah; Abdullahi, Leila; Collins, Jamie; Muloiwa, Rudzani; Hussey, Gregory; Kagina, Benjamin

2017-11-14

Varicella zoster virus (VZV) causes varicella and herpes zoster. These vaccine preventable diseases are common globally. Most available data on VZV epidemiology are from industrialised temperate countries and cannot be used to guide decisions on the immunization policy against VZV in Africa. This systematic review aims to review the published data on VZV morbidity and mortality in Africa. All published studies conducted in Africa from 1974 to 2015 were eligible. Eligible studies must have reported any VZV epidemiological measure (incidence, prevalence, hospitalization rate and mortality rate). For inclusion in the review, studies must have used a defined VZV case definition, be it clinical or laboratory-based. Twenty articles from 13 African countries were included in the review. Most included studies were cross-sectional, conducted on hospitalized patients, and half of the studies used varying serological methods for diagnosis. VZV seroprevalence was very high among adults. Limited data on VZV seroprevalence in children showed very low seropositivity to anti-VZV antibodies. Co-morbidity with VZV was common. There is lack of quality data that could be used to develop VZV control programmes, including vaccination, in Africa. PROSPERO 2015: CRD42015026144 .

Simian Varicella Virus Infection of Rhesus Macaques Recapitulates Essential Features of Varicella Zoster Virus Infection in Humans

PubMed Central

Messaoudi, Ilhem; Barron, Alexander; Wellish, Mary; Engelmann, Flora; Legasse, Alfred; Planer, Shannon; Gilden, Don; Nikolich-Zugich, Janko; Mahalingam, Ravi

2009-01-01

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation. PMID:19911054

Simian varicella virus infection of rhesus macaques recapitulates essential features of varicella zoster virus infection in humans.

PubMed

Messaoudi, Ilhem; Barron, Alexander; Wellish, Mary; Engelmann, Flora; Legasse, Alfred; Planer, Shannon; Gilden, Don; Nikolich-Zugich, Janko; Mahalingam, Ravi

2009-11-01

Simian varicella virus (SVV), the etiologic agent of naturally occurring varicella in primates, is genetically and antigenically closely related to human varicella zoster virus (VZV). Early attempts to develop a model of VZV pathogenesis and latency in nonhuman primates (NHP) resulted in persistent infection. More recent models successfully produced latency; however, only a minority of monkeys became viremic and seroconverted. Thus, previous NHP models were not ideally suited to analyze the immune response to SVV during acute infection and the transition to latency. Here, we show for the first time that intrabronchial inoculation of rhesus macaques with SVV closely mimics naturally occurring varicella (chickenpox) in humans. Infected monkeys developed varicella and viremia that resolved 21 days after infection. Months later, viral DNA was detected only in ganglia and not in non-ganglionic tissues. Like VZV latency in human ganglia, transcripts corresponding to SVV ORFs 21, 62, 63 and 66, but not ORF 40, were detected by RT-PCR. In addition, as described for VZV, SVV ORF 63 protein was detected in the cytoplasm of neurons in latently infected monkey ganglia by immunohistochemistry. We also present the first in depth analysis of the immune response to SVV. Infected animals produced a strong humoral and cell-mediated immune response to SVV, as assessed by immunohistology, serology and flow cytometry. Intrabronchial inoculation of rhesus macaques with SVV provides a novel model to analyze viral and immunological mechanisms of VZV latency and reactivation.

Childhood varicella-zoster virus vaccination in Belgium: cost-effective only in the long run or without exogenous boosting?

PubMed

Bilcke, Joke; van Hoek, Albert Jan; Beutels, Philippe

2013-04-01

To assess the effectiveness and cost-effectiveness of a universal childhood varicella-zoster vaccination programme in Belgium (1) using the most recent Belgian data on varicella-zoster burden, (2) exploring different options for the timing of the second dose, (3) obtaining results with and without exogenous natural boosting, and (4) investigating the possible additional benefit of zoster booster vaccination for adults at age 50 or 60 y. An extensively studied and improved dynamic model is used to estimate primary and breakthrough chickenpox and zoster cases over time. For a range of vaccination options, we compared the direct costs (health care payer perspective) and health outcomes (including Quality-Adjusted Life-Years (QALYs) lost) associated with chickenpox and herpes zoster. Estimates of social contact patterns, health care use, costs and QALY losses are almost exclusively based on Belgian databases and surveys. If exogenous natural boosting exists, a net loss in QALYs is expected for several decades after implementing a universal chickenpox vaccination programme, due to an increase in zoster mainly in persons aged 50-80 y. This result holds also for scenarios that minimise or counteract the expected increase in zoster incidence (e.g. additional booster vaccinations in adults). However, if the boosting hypothesis is not true or if costs and QALYs are cumulated over at least 33 to more than 100 y after vaccination (depending on the assumptions made), different options for universal 2-dose vaccination against chickenpox in Belgium would be cost-effective at a vaccine price of €43/dose or lower.

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa.

PubMed

Rice, Philip S

2011-04-23

Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection. Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity. The hypothesis is testable by exposing different virus genotypes to ultra-violet radiation and quantifying virus survival by plaque forming

Ultra-violet radiation is responsible for the differences in global epidemiology of chickenpox and the evolution of varicella-zoster virus as man migrated out of Africa

PubMed Central

2011-01-01

Background Of the eight human herpes viruses, varicella-zoster virus, which causes chickenpox and zoster, has a unique epidemiology. Primary infection is much less common in children in the tropics compared with temperate areas. This results in increased adult susceptibility causing outbreaks, for example in health-care workers migrating from tropical to temperate countries. The recent demonstration that there are different genotypes of varicella-zoster virus and their geographic segregation into tropical and temperate areas suggests a distinct, yet previously unconsidered climatic factor may be responsible for both the clinical and molecular epidemiological features of this virus infection. Presentation of the hypothesis Unlike other human herpes viruses, varicella-zoster virus does not require intimate contact for infection to occur indicating that transmission may be interrupted by a geographically restricted climatic factor. The factor with the largest difference between tropical and temperate zones is ultra-violet radiation. This could reduce the infectiousness of chickenpox cases by inactivating virus in vesicles, before or after rupture. This would explain decreased transmissibility in the tropics and why the peak chickenpox incidence in temperate zones occurs during winter and spring, when ultra-violet radiation is at its lowest. The evolution of geographically restricted genotypes is also explained by ultra-violet radiation driving natural selection of different virus genotypes with varying degrees of resistance to inactivation, tropical genotypes being the most resistant. Consequently, temperate viruses should be more sensitive to its effects. This is supported by the observation that temperate genotypes are found in the tropics only in specific circumstances, namely where ultra-violet radiation has either been excluded or significantly reduced in intensity. Testing the Hypothesis The hypothesis is testable by exposing different virus genotypes to ultra

Phosphorylation and nuclear localization of the varicella-zoster virus gene 63 protein.

PubMed Central

Stevenson, D; Xue, M; Hay, J; Ruyechan, W T

1996-01-01

The protein encoded by varicella-zoster virus open reading frame 63 and carboxy-terminal deletions of the same were expressed either as fusion proteins at the carboxy terminus of the maltose-binding protein in Escherichia coli or independently in transfected mammalian cells. The truncations contained amino acids 1 to 142 (63 delta N) or 1 to 210 (63 delta K) of the complete 278-amino-acid primary sequence. Recombinant casein kinase II phosphorylated the 63F and 63 delta KF fusion proteins in vitro but did not phosphorylate the 63 delta NF fusion protein, implying that phosphorylation occurred between amino acids 142 and 210. Immunoprecipitation of 35S- or 32P-labelled extracts of cells transfected with plasmids expressing 63, 63 delta N, or 63 delta K also indicated that in situ phosphorylation most likely occurred between amino acids 142 and 210. These combined results suggest that casein kinase II plays a significant role in the phosphorylation of the varicella-zoster virus 63 protein. Indirect immunofluorescence of transfected cells indicated nuclear localization of the 63 protein and cytoplasmic localization of 63 delta K and 63 delta N, implying a requirement for sequences between amino acids 210 and 278 for efficient nuclear localization. PMID:8523589

Varicella-zoster virus vaccine, successes and difficulties.

PubMed

Sarkadi, Julia

2013-12-01

Despite intensive efforts in recent decades to develop preventive or therapeutic vaccines against diseases caused by herpes simplex virus (HSV), or varicella-zoster virus (VZV), members of the Alpha herpes virinae subfamily of human herpes viruses,a safe and efficient vaccine has been approved for commercial development only against VZV. The VZV vaccine contains a live attenuated strain, OKA. It consists of amixture of at least 13 subpopulations of viruses, all with deletions, insertions or mutations in the genome; the most common mutations are observed in the open reading frame 62 (ORF62). Experience over more than 30 years in Japan, the USA and other countries where VZV vaccination is provided has demonstrated that the vaccine is safe and the effectiveness of two doses compared to unvaccinated children is 98-99%. When administered in a higher dose to stimulate the declining cell-mediated immunity, the same vaccine has been shown to reduce the incidence and severity of herpes zoster in immunocompetent individuals older than 60 years. Vaccination of immuno-compromised subjects with this VZV vaccine is problematic and various strategies need to be explored. Differences in the pathomechanisms of infection, latency and immune evasion of VZV and HSV, together with host genetic factors, may explain the availability of the successful VZV vaccine and the failures of the past HSV vaccine candidates.

Herpes zoster producing temporary erectile dysfunction.

PubMed

Rix, G H; Carroll, D N; MacFarlane, J R

2001-12-01

Varicella Zoster affecting the sacral dermatomes is a rare but well recognised cause of urinary retention. Only one case of erectile dysfunction associated with Varicella Zoster has previously been described, which was longstanding, but no cases of transient erectile dysfunction following Zoster infection are recorded. We present one such case.

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol

PubMed Central

Hussey, Hannah S; Abdullahi, Leila H; Collins, Jamie E; Muloiwa, Rudzani; Hussey, Gregory D; Kagina, Benjamin M

2016-01-01

Introduction Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Methods and analysis Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Ethics and dissemination As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated

Varicella zoster virus-associated morbidity and mortality in Africa: a systematic review protocol.

PubMed

Hussey, Hannah S; Abdullahi, Leila H; Collins, Jamie E; Muloiwa, Rudzani; Hussey, Gregory D; Kagina, Benjamin M

2016-04-20

Varicella zoster virus (VZV) causes varicella (chicken pox) and herpes zoster (shingles). Worldwide, these diseases are associated with significant morbidity. Most of the epidemiological data on VZV come from high income countries. There are few data on VZV in Africa, where tropical climates and high HIV/AIDS prevalence rates are expected to impact the epidemiology of VZV. Safe and effective vaccinations for both varicella and herpes zoster exist, but are not routinely used in Africa. There are very few data available on VZV disease burden in Africa to guide the introduction of these vaccines on the continent. Our aim is to conduct a systematic review of the VZV-associated morbidity and mortality in Africa, which will provide critical information that could be used to develop vaccination policies against these diseases in Africa. Electronic databases will be searched and all studies published after 1974 that meet predefined criteria will be assessed. The primary outcomes for the study are VZV incidence/prevalence, hospitalisation rates and total death rates. The secondary outcome for this study is the proportion of VZV hospitalisations and/or deaths associated with HIV/AIDS. Two reviewers will screen the titles and abstracts, and then independently review the full texts, to determine if studies are eligible for inclusion. A risk of bias and quality assessment tool will be used to score all included studies. Following standardised data extraction, a trend analysis using R-programming software will be conducted to investigate the trend of VZV. Depending on the characteristics of included studies, subgroup analyses will be performed. This review will be reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. As this is a protocol for a systematic review, which will use already published data, no ethics approval is required. Findings will be disseminated in peer-reviewed journals. CRD42015026144. Published by

Herpes zoster in childhood.

PubMed

Leung, Alexander K C; Robson, W Lane M; Leong, Alexander G

2006-01-01

Herpes zoster is caused by reactivation of latent varicella-zoster virus that resides in a dorsal root ganglion. Herpes zoster can develop any time after a primary infection. Because varicella vaccine is a live attenuated virus, herpes zoster can develop in a vaccine recipient. The incidence of herpes zoster among vaccine recipients is about 14 cases per 100,000 person-years. In young children, herpes zoster has a predilection for areas supplied by the cervical and sacral dermatomes. The most common complications are secondary bacterial infection, depigmentation, and scarring. Although the diagnosis of herpes zoster is based on a distinct clinical appearance, viral DNA analysis of the lesion by polymerase chain reaction or restriction fragment length polymorphism is necessary to differentiate wild from vaccine-type viruses. Acyclovir is the treatment of choice for herpes zoster.

Effectiveness of varicella vaccine in children infected with HIV.

PubMed

Son, Moeun; Shapiro, Eugene D; LaRussa, Philip; Neu, Natalie; Michalik, David E; Meglin, Michelle; Jurgrau, Andrea; Bitar, Wally; Vasquez, Marietta; Flynn, Patricia; Gershon, Anne A

2010-06-15

Although varicella vaccine is given to clinically stable human immunodeficiency virus (HIV)-infected children, its effectiveness is unknown. We assessed its effectiveness by reviewing the medical records of closely monitored HIV-infected children, including those receiving highly active antiretroviral therapy (HAART) between 1989 and 2007. Varicella immunization and development of varicella or herpes zoster were noted. Effectiveness was calculated by subtracting from 1 the rate ratios for the incidence rates of varicella or herpes zoster in vaccinated versus unvaccinated children. The effectiveness of the vaccine was 82% (95% confidence interval [CI], 24%-99%; P = .01) against varicella and was 100% (95% CI, 67%-100%; P < .001) against herpes zoster. When the analysis was controlled for receipt of HAART, vaccination remained highly protective against herpes zoster.

Perspectives on the Impact of Varicella Immunization on Herpes Zoster. A Model-Based Evaluation from Three European Countries

PubMed Central

Poletti, Piero; Melegaro, Alessia; Ajelli, Marco; del Fava, Emanuele; Guzzetta, Giorgio; Faustini, Luca; Scalia Tomba, Giampaolo; Lopalco, Pierluigi; Rizzo, Caterina; Merler, Stefano; Manfredi, Piero

2013-01-01

The introduction of mass vaccination against Varicella-Zoster-Virus (VZV) is being delayed in many European countries because of, among other factors, the possibility of a large increase in Herpes Zoster (HZ) incidence in the first decades after the initiation of vaccination, due to the expected decline of the boosting of Cell Mediated Immunity caused by the reduced varicella circulation. A multi-country model of VZV transmission and reactivation, is used to evaluate the possible impact of varicella vaccination on HZ epidemiology in Italy, Finland and the UK. Despite the large uncertainty surrounding HZ and vaccine-related parameters, surprisingly robust medium-term predictions are provided, indicating that an increase in HZ incidence is likely to occur in countries where the incidence rate is lower in absence of immunization, possibly due to a higher force of boosting (e.g. Finland), whereas increases in HZ incidence might be minor where the force of boosting is milder (e.g. the UK). Moreover, a convergence of HZ post vaccination incidence levels in the examined countries is predicted despite different initial degrees of success of immunization policies. Unlike previous model-based evaluations, our investigation shows that after varicella immunization an increase of HZ incidence is not a certain fact, rather depends on the presence or absence of factors promoting a strong boosting intensity and which might or not be heavily affected by changes in varicella circulation due to mass immunization. These findings might explain the opposed empirical evidences observed about the increases of HZ in sites where mass varicella vaccination is ongoing. PMID:23613740

Herpes zoster involving penis and scrotum: an unusual occurrence.

PubMed

Arshad, Abdul Rehman; Alvi, Kamran Yousaf; Chaudhary, Ammad Akram

2015-03-01

Herpes zoster is an infectious vesicular skin rash in a dermatomal distribution caused by Varicella zoster virus. It occurs very uncommonly in sacral dermatomes. We describe a case with rash on penis and scrotum due to involvement of S2 dermatome in a young male. The disease followed an uneventful course and the patient recovered completely without any sequelae or complications. This case is being presented to highlight its unusual location and to discuss differentiation from another viral infection commonly seen at this site.

Lessons from an Outbreak of Varicella Infection in Pediatric Hemato-Oncology Patients.

PubMed

Manistarski, Michal; Levin, Dror; Dvir, Rina; Berger-Achituv, Sivan; Rosenfeld Keidar, Hila; Grisaru-Soen, Galia; Carmeli, Yehuda; Elhasid, Ronit

2018-01-25

Immunocompromized patients exposed to varicella may experience significant morbidity and a 7% mortality rate. Management and outcome of an outbreak of varicella infection among hospitalized pediatric hemato-oncology patients using the guidelines of the American Academy of Pediatrics Committee on Infectious Diseases is presented. This retrospective study describes an outbreak of varicella infection between February 2011 and June 2011. Data were retrieved from the patients' files. Positive PCR results for varicella zoster virus from vesicular skin lesions were used for the diagnosis of varicella infection. Twelve pediatric hemato-oncology patients experienced 13 episodes of varicella infection, eleven underwent one episode each and one patient had two episodes. All exposed patients without immunity received varicella zoster immune globulins or intravenous immunoglobulin and were isolated as recommended by the guidelines. Infected patients received intravenous acyclovir. One patient with acute lymphoblastic leukemia at induction chemotherapy died. All the other patients survived. Our experience in the management of hospitalized immunocompromised patients exposed to varicella was that a positive IgG serology did not confer protection after exposure to varicella infection and thus can not serve as a marker for immunity. Unlike the isolation period sufficient for immunocompetent patients, crusted lesions can be contagious and thus require extended isolation for immunocompromised patients. Patients receiving rituximab are at greater risk of having persistent or recurrent disease. Studies with a larger sample size should be performed in order to better assess the management of immunocompromized patients exposed to varicella.

Altered phenotype and functionality of varicella zoster virus-specific cellular immunity in individuals with active infection.

PubMed

Schub, David; Janssen, Eva; Leyking, Sarah; Sester, Urban; Assmann, Gunter; Hennes, Pia; Smola, Sigrun; Vogt, Thomas; Rohrer, Tilman; Sester, Martina; Schmidt, Tina

2015-02-15

Varicella zoster virus (VZV) establishes lifelong persistence and may reactivate in individuals with impaired immune function. To investigate immunologic correlates of protection and VZV reactivation, we characterized specific immunity in 207 nonsymptomatic immunocompetent and 132 immunocompromised individuals in comparison with patients with acute herpes zoster. VZV-specific CD4 T cells were quantified flow cytometrically after stimulation and characterized for expression of interferon-γ, interleukin 2, and tumor necrosis factor α and surface markers for differentiation (CD127) and anergy (cytotoxic T lymphocyte antigen 4 [CTLA-4] and programmed death [PD]-1). Immunoglobulin G and A levels were quantified using an enzyme-linked immunosorbent assay. In healthy individuals, VZV-specific antibody and T-cell levels were age dependent, with the highest median VZV-specific CD4 T-cell frequencies of 0.108% (interquartile range, 0.121%) during adolescence. VZV-specific T-cell profiles were multifunctional with predominant expression of all 3 cytokines, CD127 positivity, and low expression of CTLA-4 and PD-1. Nonsymptomatic immunocompromised patients had similar VZV-specific immunologic properties except for lower T-cell frequencies (P<.001) and restricted cytokine expression. In contrast, significantly elevated antibody- and VZV-specific CD4 T-cell levels were found in patients with zoster. Their specific T cells showed a shift in cytokine expression toward interferon γ single positivity, an increase in CTLA-4 and PD-1, and a decrease in CD127 expression (all P<.001). This phenotype normalized after resolution of symptoms. VZV-specific CD4-T cells in patients with zoster bear typical features of anergy. This phenotype is reversible and may serve as adjunct tool for monitoring VZV reactivations in high-risk patients. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions

Chickenpox (Varicella) Photos

MedlinePlus

... advised. Click on any image to enlarge it. Images of People Affected by the Disease Chickenpox in ... vaccinated child. Courtesy of Varicella Active Surveillance Project Images of Varicella Zoster Virus PHIL Photo ID# 2791 ...

Is chickenpox so bad, what do we know about immunity to varicella zoster virus, and what does it tell us about the future?

PubMed

Gershon, Anne A

2017-06-01

Varicella and zoster continue to cause significant morbidity and even mortality in children and adults. Complications include bacterial superinfection, central nervous system manifestations such as meningitis, encephalitis, and cerebellar ataxia, and pain syndromes especially post herpetic neuralgia. Many developed countries but not all, are now administering live attenuated varicella vaccine routinely, with a decrease in the incidence of disease, providing personal and herd immunity. There is some controversy, however, in some countries concerning whether a decrease in the circulation of wild type virus will result in loss of immunity to VZV in persons who have already had varicella. This manuscript reviews the complications of varicella and zoster in detail, the reasons for development of vaccines against these diseases, complications of vaccinations, and mechanisms by which immunity to this virus develops and is maintained. There are strong indications that the best way to control disease and spread of this virus is by vaccination against both. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Aberrant intracellular localization of Varicella-Zoster virus regulatory proteins during latency

PubMed Central

Lungu, Octavian; Panagiotidis, Christos A.; Annunziato, Paula W.; Gershon, Anne A.; Silverstein, Saul J.

1998-01-01

Varicella-Zoster virus (VZV) is a herpesvirus that becomes latent in sensory neurons after primary infection (chickenpox) and subsequently may reactivate to cause zoster. The mechanism by which this virus maintains latency, and the factors involved, are poorly understood. Here we demonstrate, by immunohistochemical analysis of ganglia obtained at autopsy from seropositive patients without clinical symptoms of VZV infection that viral regulatory proteins are present in latently infected neurons. These proteins, which localize to the nucleus of cells during lytic infection, predominantly are detected in the cytoplasm of latently infected neurons. The restriction of regulatory proteins from the nucleus of latently infected neurons might interrupt the cascade of virus gene expression that leads to a productive infection. Our findings raise the possibility that VZV has developed a novel mechanism for maintenance of latency that contrasts with the transcriptional repression that is associated with latency of herpes simplex virus, the prototypic alpha herpesvirus. PMID:9618542

Subclinical Reactivation and Shed of Infectious Varicella Zoster Virus in Saliva of Astronauts

NASA Technical Reports Server (NTRS)

Cohrs, Randall J.; Mehta, Satish K.; Schmid, D. Scott; Gilden, Donald H.; Pierson, Duane L.

2007-01-01

We have previously detected VZV in healthy astronauts both during spaceflight and shortly after landing. Herein, we show that VZV shed in seropositive astronauts is infectious. A total of 40 saliva samples were obtained from each of the 3 astronauts. From each astronaut, 14 samples were taken 109 to 133 days before liftoff, 1 sample was taken every day during 12 days in space, and one sample was taken for 14 consecutive days beginning the second day after landing. Quantitative PCR was used to detect VZV DNA in saliva. None of 42 preflight saliva samples contained VZV DNA. VZV DNA was detected in saliva from 2 of 3 astronauts. In 1 astronaut, 6 of 12 samples obtained during space flight contained 120 to 2,500 copies of VZV DNA per ml; after landing, 1250 copies of VZV DNA were present on day 2, 45 copies on day 3, and 110 copies on day 5. All samples taken 6 to 15 days after touchdown were negative for VZV DNA. In the second astronaut, 5 of 12 samples obtained during space flight contained 18 to 650 copies of VZV DNA per ml; after landing, 560 copies of VZV DNA were present in saliva on day 2, 340 copies on day 4, 45 copies on day 5, and 23 copes on day 6. All samples taken 7 to 15 days after touchdown were negative for VZV DNA. Saliva taken 2 to 6 days after landing from all 3 astronauts was cultured on human fetal lung cells. After one subcultivation, a cytopathic effect developed in cultures inoculated with saliva from the two astronauts whose saliva contained VZV DNA. Both PCR and immunostaining identified the isolates to be VZV and not HSV-1. Importantly, the astronaut in whom no VZV was detected had a history of zoster 9 years earlier. It is possible that a boost in cell-mediated immunity to VZV which is known to develop after zoster protected him from subclinical reactivation. The genotype of the two VZV isolates was determined by VZV ORF22-based PCR/sequencing along with FRET-based PCR assays that target specific nucleotide polymorphisms. Both VZV isolates

Characterization of neutralizing epitopes of varicella-zoster virus glycoprotein H.

PubMed

Akahori, Yasushi; Suzuki, Kazuhiro; Daikoku, Tohru; Iwai, Masae; Yoshida, Yoshihiro; Asano, Yoshizo; Kurosawa, Yoshikazu; Shiraki, Kimiyasu

2009-02-01

Varicella-zoster virus (VZV) glycoprotein H (gH) is the major neutralization target of VZV, and its neutralizing epitope is conformational. Ten neutralizing human monoclonal antibodies to gH were used to map the epitopes by immunohistochemical analysis and were categorized into seven epitope groups. The combinational neutralization efficacy of two epitope groups was not synergistic. Each epitope was partially or completely resistant to concanavalin A blocking of the glycomoiety of gH, and their antibodies inhibited the cell-to-cell spread of infection. The neutralization epitope comprised at least seven independent protein portions of gH that served as the target to inhibit cell-to-cell spread.

Disseminated Herpes Zoster Ophthalmicus in an Immunocompetent 8-Year Old Boy

PubMed Central

Oladokun, Regina Eziuka; Olomukoro, Chikodili N; Owa, Adewale B.

2013-01-01

Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age. In the current report, he presented during an on-going chicken pox outbreak and survived with no significant complications. A breakthrough varicella virus re-infection or a reactivation is possible, both of which could present as zoster. This case emphasizes the need for prevention of varicella virus infection through universal childhood immunization and effective infection control strategies in health care settings. PMID:24765504

Disseminated herpes zoster ophthalmicus in an immunocompetent 8-year old boy.

PubMed

Oladokun, Regina Eziuka; Olomukoro, Chikodili N; Owa, Adewale B

2013-08-02

Varicella results from a primary infection with the varicella virus while herpes zoster is caused by a reactivation of a latent infection. Dissemination of herpes zoster is uncommon in immunocompetent individuals. Reports of disseminated herpes zoster in children are even less common than in adults. An unusual case of disseminated herpes zoster ophthalmicus in an 8-year old immunocompetent black boy is presented. He had a previous primary Varicella zoster virus infection at three years of age. In the current report, he presented during an on-going chicken pox outbreak and survived with no significant complications. A breakthrough varicella virus re-infection or a reactivation is possible, both of which could present as zoster. This case emphasizes the need for prevention of varicella virus infection through universal childhood immunization and effective infection control strategies in health care settings.

Immunohistochemical identification of varicella-zoster virus gene 63-encoded protein (IE63) and late (gE) protein on smears and cutaneous biopsies: implications for diagnostic use.

PubMed

Nikkels, A F; Debrus, S; Sadzot-Delvaux, C; Piette, J; Rentier, B; Piérard, G E

1995-12-01

Early and specific recognition of varicella zoster virus (VZV) infection is of vital concern in immunocompromised patients. The aim of this study was to compare the diagnostic accuracy of histochemical and immunohistochemical identification of the VZV ORF63 encoded protein (IE63) and of the VZV late protein gE on smears and formalin-fixed paraffin-embedded skin sections taken from lesions clinically diagnosed as varicella (n = 15) and herpes zoster (n = 51). Microscopic examinations of Tzanck smears and skin sections yielded a diagnostic accuracy of Herpesviridae infections in 66.7% (10/15) and 92.3% (12/13) of varicella, and 74.4% (29/39) and 87.8% (43/49) of herpes zoster, respectively. Immunohistochemistry applied to varicella provided a type-specific virus diagnostic accuracy of 86.7% (13/15; IE63) and 100% (15/15; gE) on smears, and of 92.3% for both VZV proteins on skin sections. In herpes zoster, the diagnostic accuracy of immunohistochemistry reached 92.3% (36/39; IE63) and 94.9% (37/39; gE) on smears, and 91.7% (44/48; IE63) and 91.8% (45/49; gE) on skin sections. These findings indicate that the immunohistochemical detection of IE63 and gE on both smears and skin sections yields a higher specificity and sensitivity than standard microscopic assessments.

Simultaneous Occurrence of Varicella Zoster Virus-Induced Pancreatitis and Hepatitis in a Renal Transplant Recipient: A Case Report and Review of Literature

PubMed Central

Chhabra, Puneet; Ranjan, Priyadarshi; Bhasin, Deepak K

2017-01-01

Introduction: Gastrointestinal complications are common after renal transplantation, including oral lesions, esophagitis, gastritis, diarrhea, and colon carcinoma. The differential diagnosis is difficult in this scenario because multiple factors such as drugs, infections, and preexisting gastrointestinal disease come into play. Case Presentation: We report a case of varicella zoster virus-induced pancreatitis and hepatitis in a renal transplant recipient. The patient underwent renal transplantation 3 years earlier and now presented with severe pain in the epigastrium radiating to his back and had raised serum lipase levels and skin lesions characteristic of varicella. Liver enzyme levels were also elevated. He was started on a regimen of acyclovir. His pain improved in 24 hours, and liver enzyme levels returned to normal in 48 hours. Discussion: There is a paucity of literature on the simultaneous occurrence of varicella zoster virus-induced hepatitis and pancreatitis in both immunocompetent and immunocompromised patients. Our case highlights the gastrointestinal complications of varicella infection in immunocompromised patients that may precede the characteristic dermatologic manifestations, and the fact that rarely both hepatitis and pancreatitis may be seen. PMID:28333601

Childhood herpes zoster: a clustering of ten cases.

PubMed

Prabhu, Smitha; Sripathi, H; Gupta, Sanjeev; Prabhu, Mukyaprana

2009-01-01

Herpes zoster occurs due to reactivation of the latent varicella zoster virus and is usually a disease of the elderly. Childhood herpes zoster is believed to be rare, though recent studies suggest increasing incidence in children. Here we report ten cases of childhood herpes zoster, seven of which occurred within a short span of six months, at a tertiary care level hospital in Pokhara, Nepal. Only three of the ten children reported previous history of varicella infection and none was immunized against varicella. Though childhood herpes zoster accounted for less than 1% of the total zoster cases in the past, recent reports show an increase in the number of cases in apparently healthy children. So far, no studies have been done linking childhood herpes zoster with HIV, though there are many studies linking it with other immunocompromised conditions.

The association of Varicella zoster virus reactivation with Bell's palsy in children.

PubMed

Abdel-Aziz, Mosaad; Azab, Noha A; Khalifa, Badwy; Rashed, Mohammed; Naguib, Nader

2015-03-01

Bell's palsy is considered the most common cause of facial nerve paralysis in children. Although different theories have been postulated for its diagnosis, reactivation of the Varicella zoster virus (VZV) has been implicated as one of the causes of Bell's palsy. The aim of the study was to evaluate the association of Varicella-zoster virus infection with Bell's palsy and its outcome in children. A total of 30 children with Bell's palsy were recruited and were assayed for evidence of VZV infection. The severity of facial nerve dysfunction and the recovery rate were evaluated according to House-Brackmann Facial Nerve Grading Scale (HB FGS). Paired whole blood samples from all patients were obtained at their initial visit and 3 weeks later, and serum samples were analyzed for VZV IgG and IgM antibodies using ELISA. A significantly higher percentage of Bell's palsy patients were seropositive for VZV IgM antibodies than controls (36.6% of patients vs 10% of controls) while for VZV IgG antibodies the difference was statistically nonsignificant. HB FGS in Bell's palsy patients with serologic evidence of VZV recent infection or reactivation showed a statistiacally significant less cure rate than other patients. VZV reactivation may be an important cause of acute peripheral facial paralysis in children. The appropriate diagnosis of VZV reactivation should be done to improve the outcome and the cure rate by the early use of antiviral treatment. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Varicella-zoster virus seroprevalence in children and adolescents in the pre-varicella vaccine era, Germany.

PubMed

Wiese-Posselt, Miriam; Siedler, Anette; Mankertz, Annette; Sauerbrei, Andreas; Hengel, Hartmut; Wichmann, Ole; Poethko-Müller, Christina

2017-05-19

In 2004, universal childhood varicella vaccination was introduced in Germany. We aimed to determine the age-specific prevalence of anti-varicella zoster virus (VZV) IgG-antibodies among children in the pre-varicella vaccine era in Germany, to identify factors associated with VZV seropositivity, and to assess the suitability of a commercially available ELISA for VZV seroepidemiological studies by comparing it with an in-house fluorescent antibody to membrane antigen test (FAMA) as the gold standard. Serum samples of 13,433 children and adolescents aged 1-17 years included in the population-based German Health Interview and Examination Survey for Children and Adolescents (KiGGS; conducted 2003-2006) were tested for anti-VZV IgG by ELISA. All samples with equivocal ELISA results and a random selection of ELISA-negative and -positive samples were tested by FAMA. Statistical analyses were conducted using a weighting factor adjusting the study population to the total population in Germany. Seroprevalences were calculated as percentages (%) with a 95% confidence interval (CI). Odds ratios (OR) were computed by multivariate logistic regression to determine the association between socio-demographic factors and VZV seropositivity. The VZV seropositivity rate was 80.3% (95% CI: 79.3-81.3) in varicella-unvaccinated children and adolescents. VZV seropositivity rates differed significantly between age groups up to age 6 years, but not by gender. Of 118 retested serum samples with an equivocal ELISA result, 45.8% were FAMA-positive. The proportion of samples tested as false-negative in by ELISA varied by age group: 2.6% in children aged 1-6 and 9% in children aged 7-17 years. Multivariate analyses showed that age, having older siblings, and early daycare start were associated with seropositivity in preschoolers; migration background reduced the chance of VZV seropositivity in schoolchildren (OR: 0.65; 0.43-0.99) and adolescents (OR: 0.62; 0.4-0.97). In the pre-varicella vaccine

Varicella-zoster virus complements herpes simplex virus type 1 temperature-sensitive mutants.

PubMed Central

Felser, J M; Straus, S E; Ostrove, J M

1987-01-01

Varicella-zoster virus (VZV) can complement temperature-sensitive mutants of herpes simplex virus. Of seven mutants tested, two, carrying mutations in the immediate-early ICP4 and ICP27 proteins, were complemented. This complementation was not seen in coinfections with adenovirus type 5 or cytomegalovirus. Following transfection into CV-1 cells, a DNA fragment containing the VZV short repeat sequence complemented the ICP4 mutant. These data demonstrate a functional relationship between VZV and herpes simplex virus and have allowed localization of a putative VZV immediate-early gene. PMID:3023701

Varicella zoster virus-specific immune responses to a herpes zoster vaccine in elderly recipients with major depression and the impact of antidepressant medications.

PubMed

Irwin, Michael R; Levin, Myron J; Laudenslager, Mark L; Olmstead, Richard; Lucko, Anne; Lang, Nancy; Carrillo, Carmen; Stanley, Harold A; Caulfield, Michael J; Weinberg, Adriana; Chan, Ivan S F; Clair, Jim; Smith, Jeff G; Marchese, R D; Williams, Heather M; Beck, Danielle J; McCook, Patricia T; Zhang, Jane H; Johnson, Gary; Oxman, Michael N

2013-04-01

The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P<.005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine.

Management of varicella infection (chickenpox) in pregnancy.

PubMed

Shrim, Alon; Koren, Gideon; Yudin, Mark H; Farine, Dan

2012-03-01

To review the existing data regarding varicella zoster virus infection (chickenpox) in pregnancy, interventions to reduce maternal complications and fetal infection, and antepartum and peripartum management. The maternal and fetal outcomes in varicella zoster infection were reviewed, as well as the benefit of the different treatment modalities in altering maternal and fetal sequelae. Medline was searched for articles and clinical guidelines published in English between January 1970 and November 2010. The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care. Recommendations for practice were ranked according to the method described in that report (Table). 1. Varicella immunization is recommended for all non-immune women as part of pre-pregnancy and postpartum care. (II-3B) 2. Varicella vaccination should not be administered in pregnancy. However, termination of pregnancy should not be advised because of inadvertent vaccination during pregnancy. (II-3D) 3. The antenatal varicella immunity status of all pregnant women should be documented by history of previous infection, varicella vaccination, or varicella zoster immunoglobulin G serology. (III-C) 4. All non-immune pregnant women should be informed of the risk of varicella infection to themselves and their fetuses. They should be instructed to seek medical help following any contact with a person who may have been contagious. (II-3B) 5. In the case of a possible exposure to varicella in a pregnant woman with unknown immune status, serum testing should be performed. If the serum results are negative or unavailable within 96 hours from exposure, varicella zoster immunoglobulin should be administered. (III-C) 6. Women who develop varicella infection in pregnancy need to be made aware of the potential adverse maternal and fetal sequelae, the risk of transmission to the fetus, and the options available for prenatal diagnosis. (II-3C) 7. Detailed

Universal varicella vaccine immunization in Japan.

PubMed

Yoshikawa, Tetsushi; Kawamura, Yoshiki; Ohashi, Masahiro

2016-04-07

In 1974, Japanese scientists developed a live attenuated varicella vaccine based on the Oka strain. The efficacy of the vaccine for the prevention of varicella has been primarily demonstrated in studies conducted in the United States following the adoption of universal immunization using the Oka strain varicella vaccine in 1996. Although the vaccine was developed by Japanese scientists, until recently, the vaccine has been administered on a voluntary basis in Japan resulting in a vaccine coverage rate of approximately 40%. Therefore, Japan initiated universal immunization using the Oka strain varicella vaccine in November 2014. Given the transition from voluntary to universal immunization in Japan, it will also be important to monitor the epidemiology of varicella and herpes zoster. The efficacy and safety of co-administration of the varicella vaccine and measles, mumps, and rubella vaccine have been demonstrated in many countries; however, there was no data from Japan. In order to adopt the practice of universal immunization using the Oka strain varicella vaccine in Japan, data demonstrating the efficacy and safety of co-administration of varicella vaccine and measles and rubella (MR) vaccine were required. Additionally, we needed to elucidate the appropriate time interval between the first and second administrations of the vaccine. It is also important to differentiate between wild type and Oka vaccine type strains in herpes zoster patient with past history of varicella vaccine. Thus, there are many factors to consider regarding the adoption of universal immunization in Japan to control varicella zoster virus (VZV) infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

Varicella-zoster virus immunity among health care workers in Catalonia.

PubMed

Urbiztondo, L; Bayas, J M; Broner, S; Costa, J; Esteve, M; Campins, M; Borrás, E; Domínguez, A

2014-10-14

To determine varicella-zoster virus (VZV) immunity among healthcare workers (HCWs). Cross-sectional study. HCWs attending voluntary periodic health examinations between June 2008 and December 2010. Six public hospitals and five primary care areas in Catalonia, Spain. A self-administered questionnaire was given to eligible HCWs. Variables including age, sex, professional category, type of centre, history of varicella infection, and VZV vaccination were collected. The study was carried out using a convenience sample. The prevalence of antibodies and positive and negative predictive values (PPV and NPV) of the history of clinical VZV infection or vaccination were calculated. Crude and adjusted odds ratios (OR and ORa) and their 95% confidence intervals (CI) were calculated to determine the variables associated with antibody prevalence. Of 705 HCWs who agreed to participate, 644 were finally included. The overall prevalence of antibodies to varicella was 94.9% (95% CI: 92.9-96.4). Of the variables studied, only age was associated with serological susceptibility to VZV. HCWs aged 25-35 years had the highest serological susceptibility (8.1%, 95% CI: 4.6-13.0). The prevalence of antibodies was 96% in subjects reporting previous VZV infection or vaccination, compared with 93% in subjects who did not report these states or did not know. The high proportion of serologically-susceptible HCWs found in this study indicates the need to develop for screening and vaccination strategies in Catalonia. Due to the high capacity of propagation of the VZV in health settings and its consequences, VZV vaccination programmes in HCWs should be reinforced. Copyright © 2014 Elsevier Ltd. All rights reserved.

Varicella Zoster Virus–Specific Immune Responses to a Herpes Zoster Vaccine in Elderly Recipients With Major Depression and the Impact of Antidepressant Medications

PubMed Central

Irwin, Michael R.; Levin, Myron J.; Laudenslager, Mark L.; Olmstead, Richard; Lucko, Anne; Lang, Nancy; Carrillo, Carmen; Stanley, Harold A.; Caulfield, Michael J.; Weinberg, Adriana; Chan, Ivan S. F.; Clair, Jim; Smith, Jeff G.; Marchese, R. D.; Williams, Heather M.; Beck, Danielle J.; McCook, Patricia T.; Zhang, Jane H.; Johnson, Gary; Oxman, Michael N.

2013-01-01

Background. The Depression Substudy of the Shingles Prevention Study (SPS) was designed to evaluate the association between major depression and immune responses to a high-titer live attenuated varicella zoster virus (VZV) vaccine (zoster vaccine), which boosts cell-mediated immunity (CMI) to VZV and decreases the incidence and severity of herpes zoster (HZ). The Depression Substudy was a 2-year longitudinal cohort study in 92 community-dwelling adults ≥60 years of age who were enrolled in the SPS, a large, double-blind, placebo-controlled Veterans Affairs Cooperative zoster vaccine efficacy study. Methods. Forty subjects with major depressive disorder, stratified by use of antidepressant medications, and 52 age- and sex-matched controls with no history of depression or other mental illness had their VZV-CMI measured prior to vaccination with zoster vaccine or placebo and at 6 weeks, 1 year, and 2 years postvaccination. Results. Depressed subjects who were not treated with antidepressant medications had lower levels of VZV-CMI following administration of zoster vaccine than nondepressed controls or depressed subjects receiving antidepressants even when antidepressant medications failed to alter depressive symptom severity (P < .005). Similar results were obtained taking into account the time-varying status of depression and use of antidepressant medications, as well as changes in depressive symptoms, during the postvaccination period. Conclusions. Depressed patients have diminished VZV-CMI responses to zoster vaccine, and treatment with antidepressant medication is associated with normalization of these responses. Because higher levels of VZV-CMI correlate with lower risk and severity of HZ, untreated depression may increase the risk and severity of HZ and reduce the efficacy of zoster vaccine. PMID:23413415

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

PubMed

Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan; Venkatesan, Arun; Cohen, Jeffrey I

2018-01-01

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

Molecular analysis of varicella vaccines and varicella-zoster virus from vaccine-related skin lesions.

PubMed

Thiele, Sonja; Borschewski, Aljona; Küchler, Judit; Bieberbach, Marc; Voigt, Sebastian; Ehlers, Bernhard

2011-07-01

To prevent complications that might follow an infection with varicella-zoster virus (VZV), the live attenuated Oka strain (V-Oka) is administered to children in many developed countries. Three vaccine brands (Varivax from Sanofi Pasteur MSD; Varilrix and Priorix-Tetra, both from Glaxo-Smith-Kline) are licensed in Germany and have been associated with both different degrees of vaccine effectiveness and adverse effects. To identify genetic variants in the vaccines that might contribute to rash-associated syndromes, single nucleotide polymorphism (SNP) profiles of variants from the three vaccines and rash-associated vaccine-type VZV from German vaccinees were quantitatively compared by PCR-based pyrosequencing (PSQ). The Varivax vaccine contained an estimated 3-fold higher diversity of VZV variants, with 20% more wild-type (wt) SNPs than Varilrix and Priorix-Tetra. These minor VZV variants in the vaccines were identified by analyzing cloned full-length open reading frame (ORF) orf62 sequences by chain termination sequencing and PSQ. Some of these sequences amplified from vaccine VZV were very similar or identical to those of the rash-associated vaccine-type VZV from vaccinees and were almost exclusively detected in Varivax. Therefore, minorities of rash-associated VZV variants are present in varicella vaccine formulations, and it can be concluded that the analysis of a core set of four SNPs is required as a minimum for a firm diagnostic differentiation of vaccine-type VZV from wt VZV.

Direct transfer of viral and cellular proteins from varicella-zoster virus-infected non-neuronal cells to human axons.

PubMed

Grigoryan, Sergei; Yee, Michael B; Glick, Yair; Gerber, Doron; Kepten, Eldad; Garini, Yuval; Yang, In Hong; Kinchington, Paul R; Goldstein, Ronald S

2015-01-01

Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk.

Direct Transfer of Viral and Cellular Proteins from Varicella-Zoster Virus-Infected Non-Neuronal Cells to Human Axons

PubMed Central

Grigoryan, Sergei; Yee, Michael B; Glick, Yair; Gerber, Doron; Kepten, Eldad; Garini, Yuval; Yang, In Hong; Kinchington, Paul R.; Goldstein, Ronald S.

2015-01-01

Varicella Zoster Virus (VZV), the alphaherpesvirus that causes varicella upon primary infection and Herpes zoster (shingles) following reactivation in latently infected neurons, is known to be fusogenic. It forms polynuclear syncytia in culture, in varicella skin lesions and in infected fetal human ganglia xenografted to mice. After axonal infection using VZV expressing green fluorescent protein (GFP) in compartmentalized microfluidic cultures there is diffuse filling of axons with GFP as well as punctate fluorescence corresponding to capsids. Use of viruses with fluorescent fusions to VZV proteins reveals that both proteins encoded by VZV genes and those of the infecting cell are transferred in bulk from infecting non-neuronal cells to axons. Similar transfer of protein to axons was observed following cell associated HSV1 infection. Fluorescence recovery after photobleaching (FRAP) experiments provide evidence that this transfer is by diffusion of proteins from the infecting cells into axons. Time-lapse movies and immunocytochemical experiments in co-cultures demonstrate that non-neuronal cells fuse with neuronal somata and proteins from both cell types are present in the syncytia formed. The fusogenic nature of VZV therefore may enable not only conventional entry of virions and capsids into axonal endings in the skin by classical entry mechanisms, but also by cytoplasmic fusion that permits viral protein transfer to neurons in bulk. PMID:25973990

Varicella Zoster Virus-Associated Necrotizing Retinitis After Chickenpox in a 10-Year-Old Female: A Case Report.

PubMed

Shin, Yong Un; Kim, Jihong; Hong, Eun Hee; Kim, Jieun; Sohn, Joo Hyun; Cho, Heeyoon

2017-10-01

A necrotizing retinitis in children is a rare but vision-threatening ocular complication of chickenpox. We report a 10-year-old girl who developed chickenpox 1 month before presenting with panuveitis and necrotizing retinitis. After prompt antiviral treatment, her inflammatory signs were resolved. Early detection and treatment of varicella zoster-associated necrotizing retinitis after chickenpox can achieve good visual outcome.

Herpes zoster in children.

PubMed

Peterson, Nathan; Goodman, Seth; Peterson, Michael; Peterson, Warren

2016-08-01

Herpes zoster (HZ) in immunocompetent children is quite uncommon. Initial exposure to the varicella-zoster virus (VZV) may be from a wild-type or vaccine-related strain. Either strain may cause a latent infection and subsequent eruption of HZ. We present a case of HZ in a 15-month-old boy after receiving the varicella vaccination at 12 months of age. A review of the literature regarding the incidence, clinical characteristics, and diagnosis of HZ in children also is provided.

Varicella Zoster Virus Necrotizing Retinitis in Two Patients with Idiopathic CD4 Lymphocytopenia.

PubMed

Gupta, Meenakashi; Jardeleza, Maria Stephanie R; Kim, Ivana; Durand, Marlene L; Kim, Leo; Lobo, Ann-Marie

2016-10-01

Progressive outer retinal necrosis (PORN) associated with varicella zoster virus (VZV) is usually diagnosed in HIV positive or immunosuppressed patients. We report two cases of immunocompetent patients with necrotizing viral retinitis found to have idiopathic CD4 lymphocytopenia. Clinical presentation, examination, imaging, and laboratory testing of two patients with VZV retinitis are presented. An HIV negative patient with history of herpes zoster presented with rapid loss of vision and examination consistent with PORN. PCR testing confirmed VZV. Lymphocytopenia was noted with a CD4 count of 25/mm(3). A second HIV negative patient presented with blurred vision and lid swelling and was found to have peripheral VZV retinitis confirmed by PCR. Laboratory workup revealed lymphocytopenia with a CD4 count of 133/mm(3). VZV necrotizing retinitis classic for PORN can occur in HIV negative patients. Idiopathic CD4 lymphocytopenia should be considered healthy patients who develop ocular infections seen in the immunocompromised.

Efficacy of varicella (VZV) vaccination: an update for the clinician

PubMed Central

Wang, Lili; Zhu, Lucy; Zhu, Hua

2016-01-01

Varicella-zoster virus (VZV) infection causes two distinct clinical conditions. Primary varicella infection results in chickenpox, a contagious rash illness typically seen among children. VZV can reactivate years after the initial infection to cause herpes zoster (HZ) and lead to post-herpetic neuralgia, a common complication resulting in persistent pain that may last for years after the zoster rash resolves. A person’s risk of having longer lasting and more severe pain associated with HZ increases with age. Since the introduction of VZV vaccines, the rates of infection, hospitalizations, and mortality have declined. In this review, we discuss in detail current VZV vaccines available for the prevention of VZV and HZ infections. Varilrix (GSK Biologicals, UK), Varivax (Merck, USA) and the combined measles, mumps, rubella, and varicella (MMRV) vaccine contain the live attenuated Oka strain of VZV for routine varicella vaccination. While Zostavax is the only HZ vaccine currently approved for use in the United States and the European Union [EMEA, 2011], a subunit vaccine candidate called HZ/su has recently shown improved efficacy for zoster prevention in two clinical trial phase III studies. VariZIG, a post-exposure prophylactic, uses zoster immune globulin to prevent VZV infection in those who have recently been in contact with VZV but lack evidence of varicella immunity and are contraindicated to receive the varicella vaccine. Further, we discuss the skin tropic and neurotropic factor VZV ORF7 gene and its involvement in varicella infection, reactivation and latency in ganglia. Ultimately, these studies can contribute to the development of a neuroattenuated vaccine candidate against varicella or a vector for delivery of other virus antigens. PMID:27551429

Identification and characterization of 20 immunocompetent patients with simultaneous varicella zoster and herpes simplex virus infection.

PubMed

Giehl, K A; Müller-Sander, E; Rottenkolber, M; Degitz, K; Volkenandt, M; Berking, C

2008-06-01

It has been shown that varicella zoster virus (VZV) and herpes simplex virus (HSV) can co-localize to the same sensory ganglion. However, only a few case reports on VZV/HSV co-infections exist. Objective To identify and characterize patients with concurrent VZV and HSV infection at the same body site. In 1718 patients, the presence of VZV and HSV in suspicious skin lesions was investigated by polymerase chain reaction analysis. Clinical characteristics of co-infected patients were compared with matched control patients infected with either VZV or HSV. The data are discussed in the context of an extensive review of the literature. Twenty (1.2%) of 1718 patients were infected with both VZV and HSV at the same body site. The mean age was 54 years (range, 2-83). The clinical diagnosis was zoster in 65%, herpes simplex in 20%, varicella in 10% and erythema multiforme in 5% of cases. The trigeminus region was affected in 60% and the trunk in 25%. Involvement of the head was most commonly associated with a severe course of disease and with older age. Simultaneous VZV/HSV infection is rare but can occur in immunocompetent patients, which is often overlooked. The majority of cases is localized to the trigeminus region and affects elderly people.

Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

PubMed

Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

2017-07-15

The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

Varicella zoster meningitis in a pregnant woman with acquired immunodeficiency syndrome.

PubMed

Jayakrishnan, Asha; Vrees, Roxanne; Anderson, Brenna

2008-10-01

Between 6000 and 7000 women in the United States infected with human immunodeficiency virus (HIV) give birth annually. It is well known that HIV-related immunosuppression significantly increases the risk for acquiring opportunistic infections (OIs). However, there is limited information regarding the relationship of pregnancy in the setting of HIV/AIDS infection, subsequent development of OIs, and maternal and fetal outcomes. A pregnant 36-year-old woman with AIDS was diagnosed with varicella zoster meningitis. Weight-based therapy with acyclovir was initiated with clinical improvement in symptoms. Care of a pregnant HIV-infected patient with an OI poses a unique diagnostic and therapeutic challenge for clinicians. Early diagnosis and initiation of appropriate treatment may provide an opportunity to improve both maternal and fetal outcomes.

Serological Evaluation of Immunity to the Varicella-Zoster Virus Based on a Novel Competitive Enzyme-Linked Immunosorbent Assay

PubMed Central

Liu, Jian; Ye, Xiangzhong; Jia, Jizong; Zhu, Rui; Wang, Lina; Chen, Chunye; Yang, Lianwei; Wang, Yongmei; Wang, Wei; Ye, Jianghui; Li, Yimin; Zhu, Hua; Zhao, Qinjian; Cheng, Tong; Xia, Ningshao

2016-01-01

Varicella-zoster virus (VZV) is a highly contagious agent of varicella and herpes zoster. Varicella can be lethal to immunocompromised patients, babies, HIV patients and other adults with impaired immunity. Serological evaluation of immunity to VZV will help determine which individuals are susceptible and evaluate vaccine effectiveness. A collection of 110 monoclonal antibodies (mAbs) were obtained by immunization of mice with membrane proteins or cell-free virus. The mAbs were well characterized, and a competitive sandwich ELISA (capture mAb: 8H6; labelling mAb: 1B11) was established to determine neutralizing antibodies in human serum with reference to the FAMA test. A total of 920 human sera were evaluated. The competitive sandwich ELISA showed a sensitivity of 95.6%, specificity of 99.77% and coincidence of 97.61% compared with the fluorescent-antibody-to-membrane-antigen (FAMA) test. The capture mAb 8H6 was characterized as a specific mAb for VZV ORF9, a membrane-associated tegument protein that interacts with glycoprotein E (gE), glycoprotein B (gB) and glycoprotein C (gC). The labelling mAb 1B11 was characterized as a complement-dependent neutralizing mAb specific for the immune-dominant epitope located on gE, not on other VZV glycoproteins. The established competitive sandwich ELISA could be used as a rapid and high-throughput method for evaluating immunity to VZV. PMID:26853741

Novel approach to differentiate subclades of varicella-zoster virus genotypes E1 and E2 in Germany.

PubMed

Schmidt-Chanasit, Jonas; Olschläger, Stephan; Bialonski, Alexandra; Heinemann, Patrick; Bleymehl, Karoline; Gross, Gerd; Günther, Stephan; Ulrich, Rainer G; Doerr, Hans Wilhelm

2009-11-01

Varicella-zoster virus (VZV) is the causative agent of chicken pox (varicella) in children and reactivation of VZV in elderly or immunocompromised persons can cause shingles (zoster). A subclade differentiation of the most prevalent VZV genotypes E1 and E2 in Germany was not possible with the current genotyping methods in use, but is highly important to understand the VZV molecular evolution in more detail and especially to follow up the routes of infection. Therefore the objective of this study was to develop a simple PCR-based method for differentiation of E1 and E2 subclades. Viral DNA was isolated from vesicle fluid samples of six selected German zoster patients and used to amplify nine complete open reading frames (ORFs) of the VZV genome by different PCR assays. Phylogenetic analysis was performed by a Bayesian approach. Based on the analysis of a total of nine ORFs, a 7482 bp stretch consisting of ORFs 5, 37 and 62 contained informative sites for identification of novel subclades E1a, E2a and E2b for VZV genotypes E1 and E2. Specific single nucleotide polymorphisms (SNPs) were demonstrated for subclades E2a and E2b within the ORFs 5, 37 and 62, whereas a subclade E1a-specific SNP was found in ORF 56. The classification of E1 and E2 subclades may facilitate a more exact and in-depth monitoring of the molecular evolution of VZV in Germany in the future.

Stress-induced subclinical reactivation of varicella zoster virus in astronauts

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Cohrs, Randall J.; Forghani, Bagher; Zerbe, Gary; Gilden, Donald H.; Pierson, Duane L.

2004-01-01

Varicella zoster virus (VZV) becomes latent in human ganglia after primary infection. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to the virus. VZV can also reactivate after surgical stress. The unexpected occurrence of thoracic zoster 2 days before space flight in a 47-year-old healthy astronaut from a pool of 81 physically fit astronauts prompted our search for VZV reactivation during times of stress to determine whether VZV can also reactivate after non-surgical stress. We examined total DNA extracted from 312 saliva samples of eight astronauts before, during, and after space flight for VZV DNA by polymerase chain reaction: 112 samples were obtained 234-265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight, only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all eight astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These results indicate that VZV can reactivate subclinically in healthy individuals after non-surgical stress. Copyright 2004 Wiley-Liss, Inc.

Concurrent detection of herpes simplex and varicella-zoster viruses by polymerase chain reaction from the same anatomic location.

PubMed

Dhiman, Neelam; Wright, Patricia A; Espy, Mark J; Schneider, Susan K; Smith, Thomas F; Pritt, Bobbi S

2011-08-01

Herpes simplex virus (HSV) and varicella-zoster virus (VZV) may cause latent infection of the same peripheral nerve ganglia. However, there are no large studies addressing the frequency of concurrent HSV/VZV PCR positivity from the same anatomic location. In an eight-year retrospective study, we observed 1.3% dual positivity from dermal, genital, and oral mucosal sources. Copyright © 2011 Elsevier Inc. All rights reserved.

Varicella-zoster virus glycoprotein expression differentially induces the unfolded protein response in infected cells

PubMed Central

Carpenter, John E.; Grose, Charles

2014-01-01

Varicella-zoster virus (VZV) is a human herpesvirus that spreads to children as varicella or chicken pox. The virus then establishes latency in the nervous system and re-emerges, typically decades later, as zoster or shingles. We have reported previously that VZV induces autophagy in infected cells as well as exhibiting evidence of the Unfolded Protein Response (UPR): XBP1 splicing, a greatly expanded Endoplasmic Reticulum (ER) and CHOP expression. Herein we report the results of a UPR specific PCR array that measures the levels of mRNA of 84 different components of the UPR in VZV infected cells as compared to tunicamycin treated cells as a positive control and uninfected, untreated cells as a negative control. Tunicamycin is a mixture of chemicals that inhibits N-linked glycosylation in the ER with resultant protein misfolding and the UPR. We found that VZV differentially induces the UPR when compared to tunicamycin treatment. For example, tunicamycin treatment moderately increased (8-fold) roughly half of the array elements while downregulating only three (one ERAD and two FOLD components). VZV infection on the other hand upregulated 33 components including a little described stress sensor CREB-H (64-fold) as well as ER membrane components INSIG and gp78, which modulate cholesterol synthesis while downregulating over 20 components mostly associated with ERAD and FOLD. We hypothesize that this expression pattern is associated with an expanding ER with downregulation of active degradation by ERAD and apoptosis as the cell attempts to handle abundant viral glycoprotein synthesis. PMID:25071735

Clinical, epidemiological and etiological studies of adult aseptic meningitis: Report of 11 cases with varicella zoster virus meningitis.

PubMed

Takeshima, Shinichi; Shiga, Yuji; Himeno, Takahiro; Tachiyama, Keisuke; Kamimura, Teppei; Kono, Ryuhei; Takemaru, Makoto; Takeshita, Jun; Shimoe, Yutaka; Kuriyama, Masaru

2017-09-30

We treated 11 cases (52.7 ± 14.9 years, all male) with varicella zoster virus (VZV) meningitis and 437 cases with adult aseptic meningitis from 2004 to 2016. The incidence rate of adult VZV meningitis in the cases with aseptic meningitis was 2.5%. Herpes zoster infections are reported to have occurred frequently in summer and autumn. VZV meningitis also occurred frequently in the similar seasons, in our patients. The diagnoses were confirmed in 9 cases with positive VZV-DNA in the cerebrospinal fluid and in 2 cases with high VZV-IgG indexes (> 2.0). For diagnosis confirmation, the former test was useful for cases within a week of disease onset, and the latter index was useful for cases after a week of disease onset. Zoster preceded the meningitis in 8 cases, while the meningitis preceded zoster in 1 case, and 2 cases did not have zoster (zoster sine herpete). Two patients were carriers of the hepatitis B virus, 1 patient was administered an influenza vaccine 4 days before the onset of meningitis, and 1 patient was orally administered prednisolone for 2 years, for treatment. Their immunological activities might have been suppressed. The neurological complications included trigeminal neuralgia, facial palsy (Ramsay Hunt syndrome), glossopharyngeal neuralgia, and Elsberg syndrome. Because the diseases in some patients can become severe, they require careful treatment.

Serology indicates cytomegalovirus infection is associated with varicella-zoster virus reactivation.

PubMed

Ogunjimi, Benson; Theeten, Heidi; Hens, Niel; Beutels, Philippe

2014-05-01

Varicella-zoster virus (VZV) causes chickenpox after which the virus remains latent in neural ganglia. Subsequent reactivation episodes occur, leading mainly to subclinical detection of VZV, but also to the clinical entity herpes zoster. These reactivations are known to occur most frequently amongst immunocompromised individuals, but the incidence of herpes zoster is also known to increase with age, supposedly as a consequence of immunosenescence. Our analysis aims to explore associations between cytomegalovirus (CMV) infection and VZV reactivation by analyzing VZV-specific antibody titers as a function of age, gender, and CMV serostatus. The analysis was repeated on measles and parvovirus B19 antibody titers. At the time of the observations, measles virus circulation was virtually eliminated, whereas parvovirus B19 circulated at lower levels than VZV. Multiple linear regression analyses, using the log-transformed antibody titers, identified a positive association between ageing and VZV antibody titers suggesting that ageing increasingly stimulates VZV reactivation. CMV infection further amplified the positive association between ageing and the reactivation rate. A negative association between CMV infection and VZV antibody titers was found in young individuals, thereby supporting the hypothesis that CMV infection may have a negative effect on the number of B-cells. However, no associations between CMV infection and measles or parvovirus B19 antibody titers occurred, but ageing tended to be associated with a decrease in the antibody titer against parvovirus B19. The combined results thus suggest that both CMV-dependent and CMV-independent immunosenescence occurs. This is supported by an in-depth analysis of VZV, measles and parvovirus B19 antibody titers. © 2013 Wiley Periodicals, Inc.

Influence of demographic changes on the impact of vaccination against varicella and herpes zoster in Germany - a mathematical modelling study.

PubMed

Horn, Johannes; Damm, Oliver; Greiner, Wolfgang; Hengel, Hartmut; Kretzschmar, Mirjam E; Siedler, Anette; Ultsch, Bernhard; Weidemann, Felix; Wichmann, Ole; Karch, André; Mikolajczyk, Rafael T

2018-01-09

Epidemiological studies suggest that reduced exposure to varicella might lead to an increased risk for herpes zoster (HZ). Reduction of exposure to varicella is a consequence of varicella vaccination but also of demographic changes. We analyzed how the combination of vaccination programs and demographic dynamics will affect the epidemiology of varicella and HZ in Germany over the next 50 years. We used a deterministic dynamic compartmental model to assess the impact of different varicella and HZ vaccination strategies on varicella and HZ epidemiology in three demographic scenarios, namely the projected population for Germany, the projected population additionally accounting for increased immigration as observed in 2015/2016, and a stationary population. Projected demographic changes alone result in an increase of annual HZ cases by 18.3% and a decrease of varicella cases by 45.7% between 1990 and 2060. Independently of the demographic scenario, varicella vaccination reduces the cumulative number of varicella cases until 2060 by approximately 70%, but also increases HZ cases by 10%. Unlike the currently licensed live attenuated HZ vaccine, the new subunit vaccine candidate might completely counteract this effect. Relative vaccine effects were consistent across all demographic scenarios. Demographic dynamics will be a major determinant of HZ epidemiology in the next 50 years. While stationary population models are appropriate for assessing vaccination impact, models incorporating realistic population structures allow a direct comparison to surveillance data and can thus provide additional input for immunization decision-making and resource planning.

[Infectious diseases].

PubMed

Chapuis-Taillard, Caroline; de Vallière, Serge; Bochud, Pierre-Yves

2009-01-07

In 2008, several publications have highlighted the role of climate change and globalization on the epidemiology of infectious diseases. Studies have shown the extension towards Europe of diseases such as Crimea-Congo fever (Kosovo, Turkey and Bulgaria), leismaniosis (Cyprus) and chikungunya virus infection (Italy). The article also contains comments on Plasmodium knowlesi, a newly identified cause of severe malaria in humans, as well as an update on human transmission of the H5NI avian influenza virus. It also mentions new data on Bell's palsy as well as two vaccines (varicella-zoster and pneumococcus), and provides a list of recent guidelines for the treatment of common infectious diseases.

Chronic active VZV infection manifesting as zoster sine herpete, zoster paresis and myelopathy.

PubMed

Morita, Y; Osaki, Y; Doi, Y; Forghani, B; Gilden, D H

2003-08-15

After lumbar-distribution zoster, an HTLV-1-seropositive woman developed chronic radicular sacral-distribution pain (zoster sine herpete), cervical-distribution zoster paresis and thoracic-distribution myelopathy. Detection of anti-varicella zoster virus (VZV) IgM and VZV IgG antibody in cerebrospinal fluid (CSF), with reduced serum/CSF ratios of anti-VZV IgG compared to normal serum/CSF ratios for albumin and total IgG, proved that VZV caused the protracted neurological complications. Diagnosis by antibody testing led to aggressive antiviral treatment and a favorable outcome.

Herpes zoster

PubMed Central

Schmader, Kenneth

2016-01-01

Synopsis Herpes zoster afflicts millions of older adults annually worldwide and causes significant suffering due to acute and chronic pain, or postherpetic neuralgia (PHN). Herpes zoster is caused by the reactivation of varicella-zoster virus (VZV) in sensory ganglia in the setting of age, disease and drug-related decline in cellular immunity to VZV. VZV-induced neuronal destruction and inflammation causes the principal problems of pain, interference with activities of daily living and reduced quality of life in older adults. To address these problems, the optimal treatment of herpes zoster requires early antiviral therapy and careful pain management. For patients who develop PHN, evidence-based pharmacotherapy using topical lidocaine patch, gabapentin, pregabalin, tricyclic antidepressants, and/or opiates can reduce pain burden. The live attenuated zoster vaccine is effective in reducing pain burden and preventing herpes zoster and PHN in older adults. PMID:17631237

Neurological Consequences of Cytomegalovirus Infection

MedlinePlus

... viruses that causes cold sores (herpes simplex virus), infectious mononucleosis (Epstein-Barr virus), and chickenpox/shingles (varicella zoster ... viruses that causes cold sores (herpes simplex virus), infectious mononucleosis (Epstein-Barr virus), and chickenpox/shingles (varicella zoster ...

Long Term Persistence of IgE Anti-Varicella Zoster Virus in Pediatric and Adult Serum Post Chicken Pox Infection and after Vaccination with Varicella Virus Vaccine.

PubMed

Smith-Norowitz, Tamar A; Josekutty, Joby; Silverberg, Jonathan I; Lev-Tov, Hadar; Norowitz, Yitzchok M; Kohlhoff, Stephan; Nowakowski, Maja; Durkin, Helen G; Bluth, Martin H

2009-12-01

The production of IgE specific to different viruses (HIV-1, Parvovirus B19, RSV), and the ability for IgE anti-HIV-1 to suppress HIV-1 production in vitro, strongly suggest an important role for IgE and/or anti viral specific IgE in viral pathogenesis. Previous studies in our laboratory were the first to report the presence of IgE anti-varicella zoster virus (VZV) in an adolescent patient with shingles. However, the presence and long term persistence of IgE anti VZV antibodies has not been studied in adults. The presence of serum IgE in addition to IgE and IgG anti-VZV antibody in sera were studied in children (N=12) (0-16 y/o) and adults (N=9) (32-76 y/o) with either a past history of (wild type) chicken pox (N=7 children, 9 adults) or 5 years after vaccination with varicella zoster (N=2 children) (Varicella virus vaccine live, Oka/Merck), as well as in non-infected subjects (N=3 children). Of the patients who had a positive history of chicken pox 13 of 16 (81%) contained IgE anti-VZV antibodies; they were both serum IgEHi (>100 IU/ml) and IgELo (<100 IU/ml). Of the patients who were vaccinated, IgE anti-VZV antibodies were undetected. In contrast, serum from the patients without a history of chicken pox or vaccination did not make either IgE or IgG anti-VZV antibodies. This is the first demonstration of the existence of IgE anti-VZV antibodies, and its long-term persistence in serum of previously infected subjects. Future studies regarding the functional role of anti-viral IgE and its relationship to VZV are warranted.

Seroepidemiologic Survey of Varicella-Zoster Virus in Korean Adults Using Glycoprotein Enzyme Immuno Assay and Fluorescent Antibody to Membrane Antigen Test

PubMed Central

Kim, Yun Hwa; Hwang, Ji Young; Lee, Kyung Min; Choi, Jin Hee; Lee, Tae Yoon; Choi, Jong Soo

2011-01-01

Background Herpes zoster (HZ) occurs mainly in the elderly and Korea is rapidly becoming an aging society. Therefore, it is important to know the immune status against varicella-zoster virus (VZV) in Korean adults to prevent the disease. Objective The aim of this study was to survey the immune status of Korean adults over 40 years of age against VZV. Methods Antibody titer was measured using a VaccZyme™ VZV glycoprotein enzyme immunoassay (gpEIA) (Binding Site, UK). Fluorescent antibody to membrane antigen (FAMA) test was performed to measure the seropositive rate. Results HZ incidence in the 214 adults enrolled in this study was 10.3%. The gpEIA geometric mean titer (GMT) was 490 mIU/ml and 90.2% of the subjects had a protective level of gpEIA antibody titer against varicella. The average gpEIA GMT of adults who previously had HZ was 1,122 mIU/ml, which was higher than the average gpEIA GMT of 457 mIU/ml in adults who had not had HZ. The FAMA positive rate was 98.6%. Conclusion Most (90.2%) Korean adults ≥40-years-of-age have a protective level of gpEIA antibody against varicella and 98.6% were FAMA seropositive. The GMT of gpEIA antibody was significantly increased with age, and was higher in adults with a history of HZ. PMID:21738361

Zeroing in on zoster: a tale of many disorders produced by one virus

PubMed Central

Galetta, Kristin M.; Gilden, Don

2015-01-01

While herpes zoster infection has been recognized since antiquity, chickenpox (varicella) was confused with smallpox until the 1800s, when both illnesses became better understood. In the 20th century, varicella zoster virus (VZV) was shown to cause varicella upon primary (first-time) infection and herpes zoster (shingles) after reactivation of latent VZV. Scientific progress over the past 50 years has rapidly advanced the understanding and prevention of disease produced by VZV. Combined imaging and virological studies continue to reveal the protean neurological, ocular and visceral disorders produced by VZV. PMID:26454371

Varicella-Zoster Virus Gastritis: Case Report and Review of the Literature.

PubMed

Nohr, Erik W; Itani, Doha M; Andrews, Christopher N; Kelly, Margaret M

2017-08-01

We report varicella-zoster virus (VZV) gastritis in a 70-year-old woman postchemotherapy for lymphoma, presenting with abdominal pain, vomiting, and delirium without rash. A gastric biopsy demonstrated viral inclusions but posed a diagnostic challenge as immunohistochemistry for cytomegalovirus and herpes simplex virus were negative, and VZV immunohistochemistry was not available. The patient developed a vesicular rash 7 days after her symptoms began. Molecular testing of the gastric biopsy and a skin swab both confirmed VZV infection. She also had probable involvement of her liver and pancreas based on imaging and serum chemistry, and possible central nervous system involvement. She recovered with appropriate antiviral therapy but later developed a postherpetic neuralgia, and chronic intrahepatic biliary strictures; liver biopsy demonstrated a cholangiopathy of uncertain etiology. A literature review of the pathogenesis, epidemiology and sequelae of VZV infection is included.

Varicella-Zoster Virus Proteins in Skin Lesions: Implications for a Novel Role of ORF29p in Chickenpox

PubMed Central

Annunziato, Paula W.; Lungu, Octavian; Panagiotidis, Christos; Zhang, Jing H.; Silvers, David N.; Gershon, Anne A.; Silverstein, Saul J.

2000-01-01

Skin biopsy samples from varicella-zoster virus (VZV)-infected patients examined by immunohistochemistry demonstrated VZV replication in nonepithelial cell types. ORF29p, a nonstructural nuclear protein, was found in nerves of two of six patients with chickenpox. In tissue culture, ORF29p was secreted by VZV-infected fibroblasts. Extracellular ORF29p can be taken up through endocytosis by human neurons, implying a novel role for this protein in pathogenesis. PMID:10644373

Spectral domain optical coherence tomography in the evaluation and management of infectious retinitis.

PubMed

Kurup, Sudhi P; Khan, Samira; Gill, Manjot K

2014-11-01

To describe spectral domain optical coherence tomography (SD-OCT) findings of infectious retinitis, including affected layer of retinal involvement, changes at the vitreoretinal interface, and response to therapy. Observational case series. A retrospective review of five patients with infectious retinitis: one with toxoplasmosis, three with herpetic retinitis secondary to cytomegalovirus, and one with herpetic retinitis secondary to varicella zoster virus. Each patient underwent a complete ophthalmologic examination, fundus photography, and SD-OCT imaging (Heidelberg Spectralis; Heidelberg Engineering, Heidelberg, Germany) of the affected retina at the initial visit with serial fundus photography and SD-OCT imaging at follow-up visits. Approval was obtained from the Institutional Review Board of Northwestern University. Spectral domain ocular coherence tomography of retinitis associated with Toxoplasma, cytomegalovirus, or varicella zoster virus demonstrates full-thickness disruption of the retinal architecture and overall thickening. This was in contrast to clinically imitating lesions such as cotton-wool spots, which only showed focal swelling of the inner retina. There was a clear demarcation between the area of active retinitis and unaffected retina. Inactivity was apparent when the previously affected thickened area became atrophic. The SD-OCT also demonstrated changes at the vitreoretinal interface where there was frequently a detachment of the posterior hyaloid (four of five cases) associated with overlying vitreous debris and formation of tractional changes. In the case of varicella zoster virus retinitis, this traction subsequently led to a total retinal detachment. In the assessment of infectious retinitides, SD-OCT is a helpful adjunct to clinical examination and fundus photography. It provides high-resolution detail regarding the border of infectious activity, the vitreoretinal interface, and the differentiation of lesions that can clinically mimic

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data.

PubMed

Goldman, G S; King, P G

2013-03-25

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services' Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost-benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)-these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to provide

Review of the United States universal varicella vaccination program: Herpes zoster incidence rates, cost-effectiveness, and vaccine efficacy based primarily on the Antelope Valley Varicella Active Surveillance Project data

PubMed Central

Goldman, G.S.; King, P.G.

2013-01-01

In a cooperative agreement starting January 1995, prior to the FDA's licensure of the varicella vaccine on March 17, the Centers for Disease Control and Prevention (CDC) funded the Los Angeles Department of Health Services’ Antelope Valley Varicella Active Surveillance Project (AV-VASP). Since only varicella case reports were gathered, baseline incidence data for herpes zoster (HZ) or shingles was lacking. Varicella case reports decreased 72%, from 2834 in 1995 to 836 in 2000 at which time approximately 50% of children under 10 years of age had been vaccinated. Starting in 2000, HZ surveillance was added to the project. By 2002, notable increases in HZ incidence rates were reported among both children and adults with a prior history of natural varicella. However, CDC authorities still claimed that no increase in HZ had occurred in any US surveillance site. The basic assumptions inherent to the varicella cost–benefit analysis ignored the significance of exogenous boosting caused by those shedding wild-type VZV. Also ignored was the morbidity associated with even rare serious events following varicella vaccination as well as the morbidity from increasing cases of HZ among adults. Vaccine efficacy declined below 80% in 2001. By 2006, because 20% of vaccinees were experiencing breakthrough varicella and vaccine-induced protection was waning, the CDC recommended a booster dose for children and, in 2007, a shingles vaccination was approved for adults aged 60 years and older. In the prelicensure era, 95% of adults experienced natural chickenpox (usually as children)—these cases were usually benign and resulted in long-term immunity. Varicella vaccination is less effective than the natural immunity that existed in prevaccine communities. Universal varicella vaccination has not proven to be cost-effective as increased HZ morbidity has disproportionately offset cost savings associated with reductions in varicella disease. Universal varicella vaccination has failed to

Expression of varicella-zoster virus and herpes simplex virus in normal human trigeminal ganglia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vafai, A.; Wellish, M.; Devlin, M.

1988-04-01

Lysates of radiolabeled explants from four human trigeminal ganglia were immunoprecipitated with antibodies to varicella-zoster virus (VZV) and to herpes simplex virus. Both herpes simplex virus- and VZV-specific proteins were detected in lysates of all four ganglia. Absence of reactivity in ganglion explants with monoclonal antibodies suggested that herpes simplex virus and VZV were not reactivated during the culture period. In situ hybridization studies demonstrated the presence of RNA transcripts from the VZV immediate early gene 63. This approach to the detection of herpes simplex virus and VZV expression in human ganglia should facilitate analysis of viral RNA and proteinsmore » in human sensory ganglia.« less

The Effects of School Holidays on Transmission of Varicella Zoster Virus, England and Wales, 1967–2008

PubMed Central

Jackson, Charlotte; Mangtani, Punam; Fine, Paul; Vynnycky, Emilia

2014-01-01

Background Changes in children’s contact patterns between termtime and school holidays affect the transmission of several respiratory-spread infections. Transmission of varicella zoster virus (VZV), the causative agent of chickenpox, has also been linked to the school calendar in several settings, but temporal changes in the proportion of young children attending childcare centres may have influenced this relationship. Methods We used two modelling methods (a simple difference equations model and a Time series Susceptible Infectious Recovered (TSIR) model) to estimate fortnightly values of a contact parameter (the per capita rate of effective contact between two specific individuals), using GP consultation data for chickenpox in England and Wales from 1967–2008. Results The estimated contact parameters were 22–31% lower during the summer holiday than during termtime. The relationship between the contact parameter and the school calendar did not change markedly over the years analysed. Conclusions In England and Wales, reductions in contact between children during the school summer holiday lead to a reduction in the transmission of VZV. These estimates are relevant for predicting how closing schools and nurseries may affect an outbreak of an emerging respiratory-spread pathogen. PMID:24932994

Live attenuated herpes zoster vaccine for HIV-infected adults.

PubMed

Shafran, S D

2016-04-01

Multiple guidelines exist for the use of live viral vaccines for measles-mumps-rubella (MMR), varicella and yellow fever in people with HIV infections, but these guidelines do not make recommendations regarding live attenuated herpes zoster vaccine (LAHZV), which is approved for people over 50 years in the general population. LAHZV is made with the same virus used in varicella vaccine. The incidence of herpes zoster remains increased in people with HIV infection, even when on suppressive antiretroviral therapy, and a growing proportion of HIV-infected patients are over 50 years of age. The purpose of this article is to review the use of varicella vaccine and LAHZV in people with HIV infection and to make recommendations about the use of LAHZV in adults with HIV infection. A PubMed search was undertaken using the terms 'herpes zoster AND HIV' and 'varicella AND HIV'. Reference lists were also reviewed for pertinent citations. Varicella vaccine is recommended in varicella-susceptible adults, as long as they have a CD4 count > 200 cells/μL, the same CD4 threshold used for MMR and yellow fever vaccines. No transmission of vaccine strain Varicella zoster virus has been documented in people with HIV infections with a CD4 count above this threshold. LAHZV was administered to 295 HIV-infected adults with a CD4 count > 200 cells/μL, and was safe and immunogenic with no cases of vaccine strain infection. It is recommended that LAHZV be administered to HIV-infected adults with a CD4 count above 200 cells/μL, the same CD4 threshold used for other live attenuated viral vaccines. © 2015 British HIV Association.

Herpes zoster of gingiva in an older woman: a rare case report.

PubMed

Chopra, Aditi; Sivaraman, Karthik; Thomas, Betsy S

2017-06-01

The aim of the article is to highlight the distinguishing features of secondary varicella gingival infection in an older women. Herpes zoster is an acute sporadic, painful viral infection in older people caused by the reactivation of the latent varicella zoster virus. Herpes zoster affecting the gingiva without any dermal lesions is a rare pathological condition that mimics many intraoral vesiculobullous lesions. The ambiguous nature of this condition creates a diagnostic dilemma. A 58-year-old woman presented with an acute, unilateral and persistent burning sensation and pain in the gingiva with desqaumating vesicullobulous lesion. The women was diagnosed with secondary varicella zoster infection. Herpes zoster of the gingiva could manifest as painful desquamative vesicular lesions, pulpal or other painful neuralgic condition in older individuals which need careful diagnosis before formulating appropiate treatment plan. © 2016 John Wiley & Sons A/S and The Gerodontology Association. Published by John Wiley & Sons Ltd.

Evolution of Cocirculating Varicella-Zoster Virus Genotypes during a Chickenpox Outbreak in Guinea-Bissau

PubMed Central

Gray, Eleanor R.; Kundu, Samit; Cooray, Samantha; Poulsen, Anja; Aaby, Peter; Breuer, Judith

2014-01-01

ABSTRACT Varicella-zoster virus (VZV), a double-stranded DNA alphaherpesvirus, is associated with seasonal outbreaks of varicella in nonimmunized populations. Little is known about whether these outbreaks are associated with a single or multiple viral genotypes and whether new mutations rapidly accumulate during transmission. Here, we take advantage of a well-characterized population cohort in Guinea-Bissau and produce a unique set of 23 full-length genome sequences, collected over 7 months from eight households. Comparative sequence analysis reveals that four distinct genotypes cocirculated among the population, three of which were present during the first week of the outbreak, although no patients were coinfected, which indicates that exposure to infectious virus from multiple sources is common during VZV outbreaks. Transmission of VZV was associated with length polymorphisms in the R1 repeat region and the origin of DNA replication. In two cases, these were associated with the formation of distinct lineages and point to the possible coevolution of these loci, despite the lack of any known functional link in VZV or related herpesviruses. We show that these and all other sequenced clade 5 viruses possess a distinct R1 repeat motif that increases the acidity of an ORF11p protein domain and postulate that this has either arisen or been lost following divergence of the major clades. Thus, sequencing of whole VZV genomes collected during an outbreak has provided novel insights into VZV biology, transmission patterns, and (recent) natural history. IMPORTANCE VZV is a highly infectious virus and the causative agent of chickenpox and shingles, the latter being particularly associated with the risk of painful complications. Seasonal outbreaks of chickenpox are very common among young children, yet little is known about the dynamics of the virus during person-to-person to transmission or whether multiple distinct viruses seed and/or cocirculate during an outbreak. In this

Evolution of cocirculating varicella-zoster virus genotypes during a chickenpox outbreak in Guinea-Bissau.

PubMed

Depledge, Daniel P; Gray, Eleanor R; Kundu, Samit; Cooray, Samantha; Poulsen, Anja; Aaby, Peter; Breuer, Judith

2014-12-01

Varicella-zoster virus (VZV), a double-stranded DNA alphaherpesvirus, is associated with seasonal outbreaks of varicella in nonimmunized populations. Little is known about whether these outbreaks are associated with a single or multiple viral genotypes and whether new mutations rapidly accumulate during transmission. Here, we take advantage of a well-characterized population cohort in Guinea-Bissau and produce a unique set of 23 full-length genome sequences, collected over 7 months from eight households. Comparative sequence analysis reveals that four distinct genotypes cocirculated among the population, three of which were present during the first week of the outbreak, although no patients were coinfected, which indicates that exposure to infectious virus from multiple sources is common during VZV outbreaks. Transmission of VZV was associated with length polymorphisms in the R1 repeat region and the origin of DNA replication. In two cases, these were associated with the formation of distinct lineages and point to the possible coevolution of these loci, despite the lack of any known functional link in VZV or related herpesviruses. We show that these and all other sequenced clade 5 viruses possess a distinct R1 repeat motif that increases the acidity of an ORF11p protein domain and postulate that this has either arisen or been lost following divergence of the major clades. Thus, sequencing of whole VZV genomes collected during an outbreak has provided novel insights into VZV biology, transmission patterns, and (recent) natural history. VZV is a highly infectious virus and the causative agent of chickenpox and shingles, the latter being particularly associated with the risk of painful complications. Seasonal outbreaks of chickenpox are very common among young children, yet little is known about the dynamics of the virus during person-to-person to transmission or whether multiple distinct viruses seed and/or cocirculate during an outbreak. In this study, we have

Use of a current varicella vaccine as a live polyvalent vaccine vector.

PubMed

Murakami, Kouki; Mori, Yasuko

2016-01-04

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The varicella vaccine was developed to control VZV infection in children. The currently available Oka vaccine strain is the only live varicella vaccine approved by the World Health Organization. We previously cloned the complete genome of the Oka vaccine strain into a bacterial artificial chromosome vector and then successfully reconstituted the virus. We then used this system to generate a recombinant Oka vaccine virus expressing mumps virus gene(s). The new recombinant vaccine may be an effective polyvalent live vaccine that provides protection against both varicella and mumps viruses. In this review, we discussed about possibility of polyvalent live vaccine(s) using varicella vaccine based on our recent studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

The natural history of varicella zoster virus infection in Norway: Further insights on exogenous boosting and progressive immunity to herpes zoster

PubMed Central

Marangi, Luigi; Mirinaviciute, Grazina; Flem, Elmira; Scalia Tomba, Gianpaolo; Guzzetta, Giorgio; Freiesleben de Blasio, Birgitte; Manfredi, Piero

2017-01-01

We use age-structured models for VZV transmission and reactivation to reconstruct the natural history of VZV in Norway based on available pre-vaccination serological data, contact matrices, and herpes zoster incidence data. Depending on the hypotheses on contact and transmission patterns, the basic reproduction number of varicella in Norway ranges between 3.7 and 5.0, implying a vaccine coverage between 73 and 80% to effectively interrupt transmission with a 100% vaccine efficacy against infection. The varicella force of infection peaks during early childhood (3–5 yrs) and shows a prolonged phase of higher risk during the childbearing period, though quantitative variations can occur depending on contact patterns. By expressing the magnitude of exogenous boosting as a proportion of the force of infection, it is shown that reactivation is well described by a progressive immunity mechanism sustained by a large, though possibly below 100%, degree of exogenous boosting, in agreement with findings from other Nordic countries, implying large reproduction numbers of boosting. Moreover, magnitudes of exogenous boosting below 40% are robustly disconfirmed by data. These results bring further insight on the magnitude of immunity boosting and its relationship with reactivation. PMID:28545047

Antibody-capture enzyme-linked immunosorbent assays that use enzyme-labelled antigen for detection of virus-specific immunoglobulin M, A and G in patients with varicella or herpes zoster.

PubMed Central

van Loon, A. M.; van der Logt, J. T.; Heessen, F. W.; Heeren, M. C.; Zoll, J.

1992-01-01

Antibody-capture enzyme-linked immunosorbent assays (AC-ELISA) which use enzyme-labelled antigen were developed for detection of varicella-zoster virus-(VZV) specific IgM, IgA and IgG antibody in patients with varicella or herpes zoster and in sera from healthy individuals. All 18 patients with varicella developed a VZV-IgM and a VZV-IgG response, 17 also a VZV-IgA response. In contrast, all 19 patients with herpes zoster were shown to be positive for VZV-IgA whereas only 13 of these reacted positively for VZV-IgM. A VZV-IgM response was detected in only two sera from 100 healthy individuals and an IgA response in only one. The presence of virus-specific IgA and IgG in the cerebrospinal fluid as determined by AC-ELISA was a useful indicator of VZV infection of the central nervous system. By AC-ELISA, VZV-IgG was detected predominantly in sera from patients with acute or recent VZV infection. Only 14 sera from 100 healthy individuals were positive for VZV-IgG by AC-ELISA, whereas all were positive by an indirect ELISA. These results indicate that AC-ELISA's may be useful assays for determination for acute or recurrent VZV infection, but are not suitable for determination of past infection with this virus. PMID:1312479

The Uncommon Localization of Herpes Zoster

PubMed Central

Cukic, Vesna

2016-01-01

Introduction: Herpes zoster is an acute, cutaneous viral infection caused by the reactivation of varicella-zoster virus (VZV) that is the cause of varicella. It is an acute neurological disease which can often lead to serious postherpetic neuralgia (PHN). Different nerves can be included with the skin rash in the area of its enervation especially cranial nerves (CV) and intercostal nerves. Case report: In this report we present a patient with herpes zoster which involved ulnar nerve with skin rash in the region of ulnar innervations in women with no disease previously diagnosed. The failure of her immune system may be explained by great emotional stress and overwork she had been exposed to with neglecting proper nutrition in that period. Conclusion: Herpes zoster may involve any nerve with characteristic skin rash in the area of its innervations, and failure in immune system which leads reactivation of VZV may be caused by other factors besides the underlying illness. PMID:26980938

Safety, humoral and cell-mediated immune responses to herpes zoster vaccine in subjects with diabetes mellitus.

PubMed

Hata, Atsuko; Inoue, Fukue; Yamasaki, Midori; Fujikawa, Jun; Kawasaki, Yukiko; Hamamoto, Yoshiyuki; Honjo, Sachiko; Moriishi, Eiko; Mori, Yasuko; Koshiyama, Hiroyuki

2013-09-01

To evaluate varicella zoster virus-specific cell-mediated immunity and humoral immunogenicity against the herpes zoster vaccine, which is licensed as the Live Varicella Vaccine (Oka Strain) in Japan, in elderly people with or without diabetes mellitus. A pilot study was conducted between May 2010 and November 2010 at Kitano Hospital, a general hospital in the city of Osaka in Japan. A varicella skin test, interferon-gamma enzyme-linked immunospot assay and immunoadherence hemagglutination tests were performed 0, 3, and 6 months after vaccination. Vaccine safety was also assessed using questionnaires for 42 days and development of zoster during the one-year observational period. We enrolled 10 healthy volunteers and 10 patients with diabetes mellitus aged 60-70 years. The live herpes zoster vaccine boosted virus-specific, cell-mediated and humoral immunity between elderly people, with or without diabetes. Moreover, no systemic adverse reaction was found. None of the study participants developed herpes zoster. The live herpes zoster vaccine was used safely. It effectively enhanced specific immunity to varicella zoster virus in older people with or without diabetes mellitus. Copyright © 2013 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

Global Mapping of O-Glycosylation of Varicella Zoster Virus, Human Cytomegalovirus, and Epstein-Barr Virus*

PubMed Central

Bagdonaite, Ieva; Nordén, Rickard; Joshi, Hiren J.; King, Sarah L.; Vakhrushev, Sergey Y.; Olofsson, Sigvard; Wandall, Hans H.

2016-01-01

Herpesviruses are among the most complex and widespread viruses, infection and propagation of which depend on envelope proteins. These proteins serve as mediators of cell entry as well as modulators of the immune response and are attractive vaccine targets. Although envelope proteins are known to carry glycans, little is known about the distribution, nature, and functions of these modifications. This is particularly true for O-glycans; thus we have recently developed a “bottom up” mass spectrometry-based technique for mapping O-glycosylation sites on herpes simplex virus type 1. We found wide distribution of O-glycans on herpes simplex virus type 1 glycoproteins and demonstrated that elongated O-glycans were essential for the propagation of the virus. Here, we applied our proteome-wide discovery platform for mapping O-glycosites on representative and clinically significant members of the herpesvirus family: varicella zoster virus, human cytomegalovirus, and Epstein-Barr virus. We identified a large number of O-glycosites distributed on most envelope proteins in all viruses and further demonstrated conserved patterns of O-glycans on distinct homologous proteins. Because glycosylation is highly dependent on the host cell, we tested varicella zoster virus-infected cell lysates and clinically isolated virus and found evidence of consistent O-glycosites. These results present a comprehensive view of herpesvirus O-glycosylation and point to the widespread occurrence of O-glycans in regions of envelope proteins important for virus entry, formation, and recognition by the host immune system. This knowledge enables dissection of specific functional roles of individual glycosites and, moreover, provides a framework for design of glycoprotein vaccines with representative glycosylation. PMID:27129252

Three year seroepidemiological study of varicella-zoster virus in São Paulo, Brazil.

PubMed

Yu, A L; Costa, J M; Amaku, M; Pannuti, C S; Souza, V A; Zanetta, D M; Burattini, M N; Massad, E; Azevedo, R S

2000-01-01

A serosurvey of varicella has been carried out in children attending the public school network of São Paulo city, Brazil, from 1992 to 1994. This study was performed in order to establish the age related prevalence of antibodies against varicella-zoster virus (VZV) and its age specific transmission dynamics pattern in these children. Among 2500 schools in the city of São Paulo public network, 304 were randomly selected; 7 children of a given age (ranging from 1 to 15 years) were randomly selected in each school, and blood samples were obtained by fingerprick into filter paper. Blood eluates were analyzed for the presence of antibodies to VZV by ELISA. Proportion of seropositivity were calculated for each age group. Samples consisted of 1768 individuals in 1992, 1758 in 1993, and 1817 in 1994, resulting in 5343 eluates. A high proportion of seropositive children from 1 to 3 years of age was observed, ascending until 10 years of age and reaching a plateau around 90% afterwards. VZV transmission in this community was similar along the three years of the study. In children attending public schools in the city of São Paulo, contact with VZV occurs in early childhood. If immunization against VZV is considered it should be introduced as soon as possible.

FV-100: the most potent and selective anti-varicella zoster virus agent reported to date.

PubMed

Migliore, Marco

2010-01-05

Bicyclic aryl furano pyrimidines represent the most potent anti-varicella zoster virus (VZV) agents reported to date. Lead compounds have 50% effective concentration (EC(50)) values in vitro that are in the subnanomolar range and selectivity index values that exceed 1 million. They have an absolute requirement for VZV thymidine kinase and most likely act as their phosphate forms. Some structural modification (such as aryl substitution in the base moiety) is tolerated, whereas little sugar modification is acceptable. The Cf1743 compound has proved to be significantly more potent than all reference anti-VZV compounds, as measured either by inhibition of infectious virus particles and/or viral DNA production; however, the high lipophilicity and very low water solubility of this compound gives poor oral bioavailability (<14%). Use of the modified cyclodextrin captisol and the synthesis of the 5'-monophosphate prodrug of Cf1743 has significantly improved water solubility, but does not give any enhancement in oral bioavailability. By contrast, the synthesis of the ether series does not give any further improvement in terms of solubility. The most promising prodrug to emerge to date is the hydrochloric salt of the 5'-valyl-ester, designated as FV-100. Its uptake into cells has been studied using fluorescent microscopy and biological assays, which have indicated that the compound is efficiently taken up by the cells after a short period of incubation.

Stress-Induced Subclinical Reactivation of Varicella Zoster Virus in Astronauts

NASA Technical Reports Server (NTRS)

Mehta, Satish K.; Pierson, Duane L.; Forghani, Bagher; Zerbe, Gary; Cohrs, Randall J.; Gilden, Donald H.

2003-01-01

After primary infection, varicella-zoster virus (VZV) becomes latent in ganglia. VZV reactivation occurs primarily in elderly individuals, organ transplant recipients, and patients with cancer and AIDS, correlating with a specific decline in cell-mediated immunity to VZV. VZV can also reactivate after surgical stress. To determine whether VZV can also reactivate after acute non-surgical stress, we examined total DNA extracted from 312 saliva samples of eight astronauts before, during and after space flight for VZV DNA by PCR: 112 samples were obtained 234 to 265 days before flight, 84 samples on days 2 through 13 of space flight, and 116 samples on days 1 through 15 after flight. Before space flight only one of the 112 saliva samples from a single astronaut was positive for VZV DNA. In contrast, during and after space flight, 61 of 200 (30%) saliva samples were positive in all 8 astronauts. No VZV DNA was detected in any of 88 saliva samples from 10 healthy control subjects. These data indicate that VZV can reactivate subclinically in healthy individuals after acute stress.

Evaluation of immunity to varicella zoster virus with a novel double antigen sandwich enzyme-linked immunosorbent assay.

PubMed

Liu, Jian; Chen, Chunye; Zhu, Rui; Ye, Xiangzhong; Jia, Jizong; Yang, Lianwei; Wang, Yongmei; Wang, Wei; Ye, Jianghui; Li, Yimin; Zhu, Hua; Zhao, Qinjian; Zhang, Jun; Cheng, Tong; Xia, Ningshao

2016-11-01

Varicella is a highly contagious disease caused by primary infection of Varicella zoster virus (VZV). Varicella can be severe or even lethal in susceptible adults, immunocompromised patients and neonates. Determination of the status of immunity to VZV is recommended for these high-risk populations. Furthermore, measurement of population immunity to VZV can help in developing proper varicella vaccination programmes. VZV glycoprotein E (gE) is an antigen that has been demonstrated to be a highly accurate indicator of VZV-specific immunity. In this study, recombinant gE (rgE) was used to establish a double antigen sandwich enzyme-linked immunosorbent assay (ELISA). The established sandwich ELISA showed high specificity and sensitivity in the detection of human sera, and it could detect VZV-specific antibodies at a concentration of 11.25 m IU/mL with a detection linearity interval of 11.25 to 360 m IU/mL (R 2  = 0.9985). The double gE antigen sandwich ELISA showed a sensitivity of 95.08 % and specificity of 100 % compared to the fluorescent-antibody-to-membrane-antigen (FAMA) test, and it showed a sensitivity of 100 % and a specificity of 94.74 % compared to a commercial neutralizing antibody detection kit. Thus, the established double antigen sandwich ELISA can be used as a sensitive and specific quantitative method to evaluate immunity to VZV.

[Acute illness following chicken pox: spleen infarction as a complication of varicella zoster infection].

PubMed

Teeninga, Nynke; Willemze, Annemieke J; Emonts, Marieke; Appel, Inge M

2011-01-01

Varicella zoster virus (VZV) infection can cause temporary acquired protein S or C deficiency via cross reacting antibodies and consequently inducing a hypercoagulable state. A 6-year-old girl with a history of congenital cardiac disease was seen at an Emergency Department with acute chest pain, dyspnoea and fever, seven days after developing chicken pox. Diagnostic tests revealed massive infarction of the spleen, and a protein S and C deficiency. In addition, blood cultures revealed a Lancefield group A β-haemolytic streptococcus (GABHS). The patient recovered fully after treatment with low molecular weight heparin and antibiotics. In this patient, septic emboli caused splenic infarction. Thromboembolic complications should be suspected in children with VZV who present with acute symptoms, in particular if bacterial superinfection is found.

Varicella zoster virus infections in Canadian children in the prevaccine era: A hospital-based study

PubMed Central

Kuhn, Susan; Davies, H Dele; Jadavji, Taj

1997-01-01

OBJECTIVE: To describe the clinical course of children admitted for varicella zoster virus (VZV) infections to a pediatric hospital before the release of VZV vaccine in Canada. DESIGN: Retrospective case series. SETTING: Tertiary pediatric hospital. Population studied was children aged 18 years or younger admitted to hospital between 1983 and 1992 who were discharged with a diagnosis of varicella or zoster. Of the 201 children who were identified, 36 were excluded, leaving 165 for analysis. RESULTS: There was a male:female ratio of 1.5:1 and a median age of 5.3 years (range two weeks to 18 years). The group included those who were previously healthy (70, 42.4%), immunocompromised (60, 36.4%), and those with nonimmunocompromising conditions (35, 21.2%). Comparison of immunocompetent and immunocompromised children revealed that complication of VZV infection was a more common reason for admission among the former (86 of 105, 81.9%, P<0.001), whereas treatment with acyclovir to limit dissemination was the most common reason in the latter (53 of 60, 88.3%, P<0.001). Skin and soft tissue infections were the most common complications in immunocompetent children (36 of 98) and those younger than five years (26 of 53), whereas pulmonary complications predominated among immunocompromised patients (eight of 98) and neurological complications in five- to 10-year-olds (16 of 36). Only one death (0.6%) occurred in an immunocompetent patient. Group A beta-hemolytic streptococci and Staphylococcus aureus caused equal numbers of secondary infections (92% of all isolates). CONCLUSIONS: Complications of VZV infections and secondary prophylactic antiviral treatment of immunocompromised children explain the majority of hospitalizations in this institution, and can be monitored after VZV vaccine introduction. Complications vary significantly with underlying healthy status and age. PMID:22346528

Vibrio vulnificus necrotizing fasciitis preceding herpes zoster

PubMed Central

Ha, Kelli Y.; Tyring, Stephen K.

2013-01-01

A 74-year-old white man presented with unilateral radicular pain extending across the left side of his chest and back. A diagnosis of postherpetic neuralgia, a sequela of herpes zoster, was made. Herpes zoster represents a reactivation of the varicella zoster virus that lies dormant in patients with past chickenpox. Risk factors for the disease include advanced age, stress, immunodeficiency, and immunosuppression. Treatment of herpes zoster entails traditional antiviral medications, while prevention may be achieved with a new prophylactic vaccine. PMID:23382617

Herpes zoster and the search for an effective vaccine

PubMed Central

Arnold, N.

2016-01-01

Summary Primary infection with varicella zoster virus (VZV), an exclusively human neurotrophic alphaherpsesvirus, results in varicella, known more commonly as chickenpox. Like other alphaherpesviruses, VZV establishes latency in the sensory ganglia and can reactivate to cause herpes zoster (also known as shingles), a painful and debilitating disease, especially in elderly and immunocompromised individuals. The overall incidence of herpes zoster in Europe and the United States is three per 1000 people, but increases sharply after 60 years of age to 10 per 1000 people. Zostavax® is a vaccine approved by the Federal Drug Administration for the prevention of herpes zoster. Unfortunately, this vaccine reduces the incidence of disease by only 51% and the incidence of post‐herpetic neuralgia by 66·5% when administered to those aged 60 and older. Moreover, it is contraindicated for individuals who are immunocompromised or receiving immunosuppressant treatments, although they are at higher risk for herpes zoster compared to immune‐competent older individuals. This paper reviews VZV pathogenesis, host responses and current vaccines available to prevent herpes zoster. PMID:27164323

Management of adult infectious encephalitis in metropolitan France.

PubMed

Goulenok, T; Buzelé, R; Duval, X; Bruneel, F; Stahl, J P; Fantin, B

2017-05-01

Infectious encephalitis is a severe disease leading to a high mortality and morbidity. The most frequent causes include Herpes simplex virus, Varicella Zoster virus, Listeria monocytogenes, and Mycobacterium tuberculosis. Urgent treatment is required (anti-infective therapy and nonspecific supportive care). The aim of this study was to define treatment strategy, empirical and after microbiological documentation at 48hours, through a systematic literature review. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Infected Peripheral Blood Mononuclear Cells Transmit Latent Varicella Zoster Virus Infection to the Guinea Pig Enteric Nervous System

PubMed Central

Gan, Lin; Wang, Mingli; Chen, Jason J.; Gershon, Michael D.; Gershon, Anne A.

2014-01-01

Latent wild-type (WT) and vaccine (vOka) varicella-zoster virus (VZV) are found in the human enteric nervous system (ENS). VZV also infects guinea pig enteric neurons in vitro, establishes latency and can be reactivated. We therefore determined whether lymphocytes infected in vitro with VZV secrete infectious virions and can transfer infection in vivo to the ENS of recipient guinea pigs. T lymphocytes (CD3-immunoreactive) were preferentially infected following co-culture of guinea pig or human peripheral blood mononuclear cells with VZV-infected HELF. VZV proliferated in the infected T cells and expressed immediate early and late VZV genes. Electron microscopy confirmed that VZV-infected T cells produced encapsulated virions. Extracellular virus, however, was pleomorphic, suggesting degradation occurred prior to release, which was confirmed by the failure of VZV-infected T cells to secrete infectious virions. Intravenous injection of WT- or vOka-infected PBMCs, nevertheless, transmitted VZV to recipient animals (guinea pig > human lymphocytes). Two days post-inoculation, lung and liver, but not gut, contained DNA and transcripts encoding ORFs 4, 40, 66 and 67. Twenty-eight days after infection, gut contained DNA and transcripts encoding ORFs 4 and 66 but neither DNA nor transcripts could any longer be found in lung or liver. In situ hybridization revealed VZV DNA in enteric neurons, which also expressed ORF63p (but not ORF68p) immunoreactivity. Observations suggest that VZV infects T cells, which can transfer VZV to and establish latency in enteric neurons in vivo. Guinea pigs may be useful for studies of VZV pathogenesis in the ENS. PMID:24965252

Systematic review of models assessing the economic value of routine varicella and herpes zoster vaccination in high-income countries.

PubMed

Damm, Oliver; Ultsch, Bernhard; Horn, Johannes; Mikolajczyk, Rafael T; Greiner, Wolfgang; Wichmann, Ole

2015-06-05

A systematic review was conducted to assess the cost-effectiveness of routine varicella and herpes zoster (HZ) vaccination in high-income countries estimated by modelling studies. A PubMed search was performed to identify relevant studies published before October 2013. Studies were included in the review if they (i) evaluated the cost-effectiveness of routine childhood or adolescent varicella vaccination and/or HZ vaccination targeting the elderly, and if they (ii) reported results for high-income countries. A total of 38 model-based studies were identified that fulfilled the inclusion criteria. Routine childhood or adolescent varicella vaccination was cost-effective or cost-saving from a payer perspective and always cost-saving from a societal perspective when ignoring its potential impact on HZ incidence due to reduced or absent exogenous boosting. The inclusion of the potential impact of childhood varicella vaccination on HZ led to net quality-adjusted life-year (QALY) losses or incremental cost-effectiveness ratios exceeding commonly accepted thresholds. Additional HZ vaccination could partially mitigate this effect. Studies focusing only on the evaluation of HZ vaccination reported a wide range of results depending on the selected target age-group and the vaccine price, but most found HZ vaccination to be a cost-effective or marginally cost-effective intervention. Cost-effectiveness of HZ vaccination was strongly dependent on the age at vaccination, the price of the vaccine, the assumed duration of protection and the applied cost per QALY threshold. While HZ vaccination is mostly considered cost-effective, cost-effectiveness of varicella vaccination primarily depends on the in- or exclusion of exogenous boosting in the model. As a consequence, clarification on the role of exogenous boosting is crucial for decision-making regarding varicella vaccination.

Integrating between-host transmission and within-host immunity to analyze the impact of varicella vaccination on zoster

PubMed Central

Ogunjimi, Benson; Willem, Lander; Beutels, Philippe; Hens, Niel

2015-01-01

Varicella-zoster virus (VZV) causes chickenpox and reactivation of latent VZV causes herpes zoster (HZ). VZV reactivation is subject to the opposing mechanisms of declining and boosted VZV-specific cellular mediated immunity (CMI). A reduction in exogenous re-exposure ‘opportunities’ through universal chickenpox vaccination could therefore lead to an increase in HZ incidence. We present the first individual-based model that integrates within-host data on VZV-CMI and between-host transmission data to simulate HZ incidence. This model allows estimating currently unknown pivotal biomedical parameters, including the duration of exogenous boosting at 2 years, with a peak threefold to fourfold increase of VZV-CMI; the VZV weekly reactivation probability at 5% and VZV subclinical reactivation having no effect on VZV-CMI. A 100% effective chickenpox vaccine given to 1 year olds would cause a 1.75 times peak increase in HZ 31 years after implementation. This increase is predicted to occur mainly in younger age groups than is currently assumed. DOI: http://dx.doi.org/10.7554/eLife.07116.001 PMID:26259874

Efficacy of live zoster vaccine in preventing zoster and postherpetic neuralgia.

PubMed

Gilden, D

2011-05-01

Declining cell-mediated immunity to varicella zoster virus (VZV) in elderly individuals results in virus reactivation manifest by zoster (shingles) and postherpetic neuralgia (PHN). To prevent virus reactivation, a new VZV vaccine (Zostavax; Merck) that boosts cell-mediated immunity to VZV was developed. The 3-year Shingles Prevention Study showed that Zostavax significantly reduced burden of disease because of zoster and PHN. Despite its cost-effectiveness for adults aged 65-75 years, as determined in the United States, Canada and UK, <2% of immunocompetent adults over age 60 years in the United States were immunized in 2007. This was because of a combination of lack of patient awareness of the vaccine, physicians' uncertainty about the duration of protection and different cost-sharing plans for immunization. Nevertheless, zoster vaccine is safe, effective and highly recommended for immunization of immunocompetent individuals over age 60 years with no history of recent zoster. © 2011 The Association for the Publication of the Journal of Internal Medicine.

Efficacy of live zoster vaccine in preventing zoster and postherpetic neuralgia

PubMed Central

Gilden, D.

2011-01-01

Declining cell-mediated immunity to varicella zoster virus (VZV) in elderly individuals results in virus reactivation manifest by zoster (shingles) and postherpetic neuralgia (PHN). To prevent virus reactivation, a new VZV vaccine (Zostavax, Merck) that boosts cell-mediated immunity to VZV was developed. The 3-year Shingles Prevention Study showed that Zostavax significantly reduced burden of disease due to zoster and PHN. Despite its cost-effectiveness for adults ages 65 to 75 years, as determined in the US, Canada and UK, less than 2% of immunocompetent adults over age 60 years in the US were immunized in 2007. This was due to a combination of lack of patient awareness of the vaccine, physicians’ uncertainty about the duration of protection, and different cost-sharing plans for immunization. Nevertheless, zoster vaccine is safe, effective, and highly recommended for immunization of immunocompetent individuals over age 60 years with no history of recent zoster. PMID:21294791

Differentiation of strains of varicella-zoster virus by changes in neutral lipid metabolism in infected cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jerkofsky, M.; De Siervo, A.J.

1986-03-01

Eleven isolates of varicella-zoster virus were tested for their effects on the incorporation of (/sup 14/C)acetate into lipids in infected human embryonic lung cells. By relative percent, all virus isolates demonstrated a shift from polar lipid synthesis to neutral lipid, especially triglyceride, synthesis. By data expressed as counts per minute per microgram of protein, the VZV strains could be separated into two groups: those strains which depressed lipid synthesis and those strains which did not depress, and may even have stimulated, lipid, especially triglyceride, synthesis. These results may be useful in understanding the development of lipid changes seen in childrenmore » affected with Reye's syndrome following chickenpox.« less

Species-specific differentiation of variola, monkeypox, and varicella-zoster viruses by multiplex real-time PCR assay.

PubMed

Maksyutov, Rinat A; Gavrilova, Elena V; Shchelkunov, Sergei N

2016-10-01

A method of one-stage rapid detection and differentiation of epidemiologically important variola virus (VARV), monkeypox virus (MPXV), and varicella-zoster virus (VZV) utilizing multiplex real-time TaqMan PCR assay was developed. Four hybridization probes with various fluorescent dyes and the corresponding fluorescence quenchers were simultaneously used for the assay. The hybridization probes specific for the VARV sequence contained FAM/BHQ1 as a dye/quencher pair; MPXV-specific, JOE/BHQ1; VZV-specific, TAMRA/BHQ2; and internal control-specific, Cy5/BHQ3. The specificity and sensitivity of the developed method were assessed by analyzing DNA of 32 strains belonging to orthopoxvirus and herpesvirus species. Copyright © 2016 Elsevier B.V. All rights reserved.

A Rare Presentation of Cranial Polyneuropathy Without Rash Caused by Varicella Zoster Virus

PubMed Central

Tecellioglu, Mehmet; Kamisli, Suat; Erbay, Mehmet Fatih; Kamisli, Ozden; Ozcan, Cemal

2017-01-01

Introduction: Varicella Zoster Virus (VZV) is associated with many disorders of the central and peripheral nervous systems including neuralgia, meningitis, meningoencephalitis, cerebellitis, vasculopathy, myelopathy, Ramsay-Hunt syndrome, and polyneuritis cranialis. Cranial nerves V, VI, VII, VIII, IX, X, XI, and/or XII may be affected. The neurological disorders caused by VZV usually present with rash, but may rarely present without rash. Case report: We herein present a case of polyneuritis cranialis without rash caused by VZV affecting cranial nerves VII, VIII, IX, and X. After excluding other causes of the condition, we diagnosed VZV infection based on VZV DNA in the CSF and an elevated anti-VZV IgG level in serum. The patient responded well to antiviral therapy. Conclusion: VZV infection should be kept in mind during the differential diagnosis of polyneuritis cranialis; it is important to note that VZV re-activation may occur without rash. PMID:28974853

Cutaneous varicella zoster virus infection following zoster vaccination: report of post-vaccination herpes zoster skin infection and literature review of zoster vaccination efficacy and guidelines.

PubMed

Stiff, Katherine M; Cohen, Philip R

2017-06-15

BackgroundHerpes zoster vaccine is currently recommended in the United States for immune competent individuals ≥60 years. The efficacy of the herpes zoster vaccine decreases with age and with time following vaccination.PurposeAn elderly man with herpes zoster following vaccination is described. The guidelines for vaccination and issues regarding re-vaccination are reviewed. PubMed was used to search the following terms: efficacy, elderly, herpes zoster, herpes zoster incidence, herpes zoster recurrence, and vaccination. The papers and relevant citations were reviewed. The clinical features of a patient with post-vaccination herpes zoster skin infection are presented; in addition, vaccine efficacy and guidelines are reviewed.ResultsA 91-year-old man, vaccinated for herpes zoster 10 years earlier, presented with crusted erosions on his face corresponding to the area innervated by the ophthalmic division of the left trigeminal nerve. Evaluation using polymerase chain reaction confirmed the diagnosis of herpes zoster.ConclusionsHerpes zoster vaccine decreases in efficacy with both age and number of years following vaccination. Therefore, booster shots or revaccination in the older population may be of benefit.

[Results of acyclovir treatment of chickenpox and herpes zoster in children with immune tolerance].

PubMed

Jankowska, H; Szczepańska-Putz, M; Wojnarowski, M

Acyclovir was used for the treatment of Varicella-zoster virus infections in 53 children (10 neonates and 43 children aged between 2 an 15 years) with immunological system deficiency hospitalized at the Department of the Infectious Diseases of Childhood in the Medical Academy in Warszawa. The obtained results of therapy were favourable except one fatal case of the child with visceral dissemination of the virus prior to acyclovir treatment. Compared with other antiviral agents used by the authors previously, acyclovir proved to be the most effective.

Is ultra-violet radiation the main force shaping molecular evolution of varicella-zoster virus?

PubMed Central

2011-01-01

Background Varicella (chickenpox) exhibits a characteristic epidemiological pattern which is associated with climate. In general, primary infections in tropical regions are comparatively less frequent among children than in temperate regions. This peculiarity regarding varicella-zoster virus (VZV) infection among certain age groups in tropical regions results in increased susceptibility during adulthood in these regions. Moreover, this disease shows a cyclic behavior in which the number of cases increases significantly during winter and spring. This observation further supports the participation of environmental factors in global epidemiology of chickenpox. However, the underlying mechanisms responsible for this distinctive disease behavior are not understood completely. In a recent publication, Philip S. Rice has put forward an interesting hypothesis suggesting that ultra-violet (UV) radiation is the major environmental factor driving the molecular evolution of VZV. Discussion While we welcomed the attempt to explain the mechanisms controlling VZV transmission and distribution, we argue that Rice's hypothesis takes lightly the circulation of the so called "temperate VZV genotypes" in tropical regions and, to certain degree, overlooks the predominance of such lineages in certain non-temperate areas. Here, we further discuss and present new information about the overwhelming dominance of temperate VZV genotypes in Mexico regardless of geographical location and climate. Summary UV radiation does not satisfactorily explain the distribution of VZV genotypes in different tropical and temperate regions of Mexico. Additionally, the cyclic behavior of varicella does not shown significant differences between regions with different climates in the country. More studies should be conducted to identify the factors directly involved in viral spreading. A better understanding of the modes of transmissions exploited by VZV and their effect on viral fitness is likely to facilitate

Type I interferon inhibits varicella-zoster virus replication by interfering with the dynamic interaction between mediator and IE62 within replication compartments.

PubMed

Ku, Chia-Chi; Chang, Yi-Hsuan; Chien, Yun; Lee, Tsung-Lin

2016-01-01

Varicella-zoster virus (VZV) is the causative agent of varicella and zoster. The immediate-early protein, IE62 is the predominant VZ virion tegument protein, transactivating the expression of all kinetic classes of VZV genes. IE62 is localized to punctae that form DNA replication compartments in the nuclei of VZV infected cells. The morphological changes and the increase in the size of replication compartments that express IE62 are correlated with production of VZ virions. Mammalian Mediator serves as a coactivator of IE62 and functions by bridging DNA-binding transcription factors¸ RNA polymerase II (RNAP II) and their target DNAs for VZV replication. While VZV is highly sensitive to type I interferons (IFNs), how IFN-α inhibits early events during VZV replication is poorly understood. In this study, we performed in situ analysis to investigate the effects of IFN-α on the dynamic interactions of IE62 with the Mediator MED25 subunit and the RNAP II negative regulator cycle-dependent kinase 8 (CDK8) in VZV infected cells by confocal immunofluorescence. We found that in addition to dose-dependent inhibition of the yields of infectious virus by IFN treatment, IFN-α prominently impeded the development of large IE62(+) nuclear compartments and significantly decreased transcription of VZV genes. Both the expression level and stable recruitment of MED25 to IE62(+) replication compartments were inhibited by IFN-α. While IFN-α treatment upregulated CDK8 expression, redistribution and recruitment of CDK8 to IE62(+) replication compartments in infected cells was not affected by VZV. IFN-α exerts multiple inhibitory activities against virus infections. In this study, we provide visionary demonstration that continuous translocation of MED25 into VZV replication compartments ensures production of virions. IFN-α greatly impedes the formation of a stable complex between IE62 and the Mediator complex thereby suppresses VZV gene transcription. Our demonstration that IFN

Zoster vaccine live for the prevention of shingles in the elderly patient

PubMed Central

Zussman, Jamie; Young, Lorraine

2008-01-01

Shingles, also known as herpes zoster, is a common disease in the elderly population that is caused by reactivation of latent varicella zoster virus. Its manifestations and complications can lead to significant short- and long-term morbidity. In 2006, the United States Food and Drug Administration approved Zoster Vaccine Live (Zostavax®) for the prevention of herpes zoster in immunocompetent adults age 60 and over. The approval was based on the results of a large, multi-center clinical trial, the Shingles Prevention Study. This study showed that vaccination significantly decreased shingles incidence, burden of illness due to disease, and the development of, and severity of postherpetic neuralgia. This review offers an overview of varicella zoster virus infection and complications, a summary of the Shingles Prevention Study, and a critical analysis designed to aid the practicing physician who has questions about vaccine administration. PMID:18686747

Neuronal Subtype and Satellite Cell Tropism Are Determinants of Varicella-Zoster Virus Virulence in Human Dorsal Root Ganglia Xenografts In Vivo

PubMed Central

Zerboni, Leigh; Arvin, Ann

2015-01-01

Varicella zoster virus (VZV), a human alphaherpesvirus, causes varicella during primary infection. VZV reactivation from neuronal latency may cause herpes zoster, post herpetic neuralgia (PHN) and other neurologic syndromes. To investigate VZV neuropathogenesis, we developed a model using human dorsal root ganglia (DRG) xenografts in immunodeficient (SCID) mice. The SCID DRG model provides an opportunity to examine characteristics of VZV infection that occur in the context of the specialized architecture of DRG, in which nerve cell bodies are ensheathed by satellite glial cells (SGC) which support neuronal homeostasis. We hypothesized that VZV exhibits neuron-subtype specific tropism and that VZV tropism for SGC contributes to VZV-related ganglionopathy. Based on quantitative analyses of viral and cell protein expression in DRG tissue sections, we demonstrated that, whereas DRG neurons had an immature neuronal phenotype prior to implantation, subtype heterogeneity was observed within 20 weeks and SGC retained the capacity to maintain neuronal homeostasis longterm. Profiling VZV protein expression in DRG neurons showed that VZV enters peripherin+ nociceptive and RT97+ mechanoreceptive neurons by both axonal transport and contiguous spread from SGC, but replication in RT97+ neurons is blocked. Restriction occurs even when the SGC surrounding the neuronal cell body were infected and after entry and ORF61 expression, but before IE62 or IE63 protein expression. Notably, although contiguous VZV spread with loss of SGC support would be predicted to affect survival of both nociceptive and mechanoreceptive neurons, RT97+ neurons showed selective loss relative to peripherin+ neurons at later times in DRG infection. Profiling cell factors that were upregulated in VZV-infected DRG indicated that VZV infection induced marked pro-inflammatory responses, as well as proteins of the interferon pathway and neuroprotective responses. These neuropathologic changes observed in sensory

Altered cellular and humoral immunity to varicella-zoster virus in patients with autoimmune diseases.

PubMed

Rondaan, Christien; de Haan, Aalzen; Horst, Gerda; Hempel, J Cordelia; van Leer, Coretta; Bos, Nicolaas A; van Assen, Sander; Bijl, Marc; Westra, Johanna

2014-11-01

Patients with autoimmune diseases such as systemic lupus erythematosus (SLE) and granulomatosis with polyangiitis (Wegener's) (GPA) have a 3-20-fold increased risk of herpes zoster compared to the general population. The aim of this study was to evaluate if susceptibility is due to decreased levels of cellular and/or humoral immunity to the varicella-zoster virus (VZV). A cross-sectional study of VZV-specific immunity was performed in 38 SLE patients, 33 GPA patients, and 51 healthy controls. Levels of IgG and IgM antibodies to VZV were measured using an in-house glycoprotein enzyme-linked immunosorbent assay (ELISA). Cellular responses to VZV were determined by interferon-γ (IFNγ) enzyme-linked immunospot (ELISpot) assay and carboxyfluorescein succinimidyl ester (CFSE) dye dilution proliferation assay. Levels of IgG antibodies to VZV were increased in SLE patients as compared to healthy controls, but levels of IgM antibodies to VZV were not. Antibody levels in GPA patients did not differ significantly from levels in healthy controls. In response to stimulation with VZV, decreased numbers of IFNγ spot-forming cells were found among SLE patients (although not GPA patients) as compared to healthy controls. Proliferation of CD4+ T cells in response to stimulation with VZV was decreased in SLE patients but not GPA patients. SLE patients have increased levels of IgG antibodies against VZV, while cellular immunity is decreased. In GPA patients, antibody levels as well as cellular responses to VZV were comparable to those in healthy controls. These data suggest that increased prevalence of herpes zoster in SLE patients is due to a poor cellular response. Vaccination strategies should aim to boost cellular immunity against VZV. Copyright © 2014 by the American College of Rheumatology.

A Real-Time PCR Assay to Identify and Discriminate Among Wild-Type and Vaccine Strains of Varicella-Zoster Virus and Herpes Simplex Virus in Clinical Specimens, and Comparison With the Clinical Diagnoses

PubMed Central

Harbecke, Ruth; Oxman, Michael N.; Arnold, Beth A.; Ip, Charlotte; Johnson, Gary R.; Levin, Myron J.; Gelb, Lawrence D.; Schmader, Kenneth E.; Straus, Stephen E.; Wang, Hui; Wright, Peter F.; Pachucki, Constance T.; Gershon, Anne A.; Arbeit, Robert D.; Davis, Larry E.; Simberkoff, Michael S.; Weinberg, Adriana; Williams, Heather M.; Cheney, Carol; Petrukhin, Luba; Abraham, Katalin G.; Shaw, Alan; Manoff, Susan; Antonello, Joseph M.; Green, Tina; Wang, Yue; Tan, Charles; Keller, Paul M.

2014-01-01

A real-time PCR assay was developed to identify varicella-zoster virus (VZV) and herpes simplex virus (HSV) DNA in clinical specimens from subjects with suspected herpes zoster (HZ; shingles). Three sets of primers and probes were used in separate PCR reactions to detect and discriminate among wild-type VZV (VZV-WT), Oka vaccine strain VZV (VZV-Oka), and HSV DNA, and the reaction for each virus DNA was multiplexed with primers and probe specific for the human β-globin gene to assess specimen adequacy. Discrimination of all VZV-WT strains, including Japanese isolates and the Oka parent strain, from VZV-Oka was based upon a single nucleotide polymorphism at position 106262 in ORF 62, resulting in preferential amplification by the homologous primer pair. The assay was highly sensitive and specific for the target virus DNA, and no cross-reactions were detected with any other infectious agent. With the PCR assay as the gold standard, the sensitivity of virus culture was 53% for VZV and 77% for HSV. There was 92% agreement between the clinical diagnosis of HZ by the Clinical Evaluation Committee and the PCR assay results. PMID:19475609

[Pain in herpes zoster: Prevention and treatment].

PubMed

Calvo-Mosquera, G; González-Cal, A; Calvo-Rodríguez, D; Primucci, C Y; Plamenov-Dipchikov, P

Shingles is a painful rash that results from reactivation of latent varicella-zoster virus in the dorsal root ganglia or cranial nerves. In this article an update is presented on the prevention and pharmacological treatment of the secondary pain from the virus infection. The most effective way to prevent post-herpetic neuralgia and its consequences is the prevention of herpes itself. A live attenuated vaccine (the Oka strain varicella zoster virus) has been available for several years, and is approved in adults aged 50 years old. Although this vaccine has shown to be effective against herpes zoster and post-herpetic neuralgia, its effectiveness decreases with age and is contraindicated in patients with some form of immunosuppression. Today the recombinant vaccines provide an alternative, and may be administered to immunocompromised persons. Copyright © 2016 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

Secular trends of chickenpox among military population in Israel in relation to introduction of varicella zoster vaccine 1979-2010.

PubMed

Mimouni, Daniel; Levine, Hagai; Tzurel Ferber, Anat; Rajuan-Galor, Inbal; Huerta-Hartal, Michael

2013-06-01

Chickenpox is a contagious disease caused by the varicella zoster virus. There is scarce data on long-term trends of chickenpox and its relation to vaccinations practices. We aimed to evaluate trends of chickenpox in a military population during the period 1979-2010 and to assess temporal associations in relation with the introduction of varicella zoster vaccine to the civilian population in Israel in 2000. The archives of the Epidemiology Section of the Israel Defense Forces, where chickenpox is a notifiable disease, were reviewed for all cases of chickenpox from January 1, 1979-December 31, 2010. Annual and monthly incidence rates were calculated and analyzed in relation to vaccine introduction. Between 1979-2000, incidence rates fluctuated around 10 cases per 10,000 soldiers without a clear trend. Since 2000 there has been a dramatic 10-fold decline in incidence, especially notable since 2008, from eight per 10,000 soldiers in 2000 to the lowest rate ever recorded, in 2009, of 0.57 cases per 10,000 soldiers. A seasonal sinusoidal pattern was clearly demonstrated, with rising incidence from November to May followed by a gradual decline to October. The results of this long-term study suggest that the rates of chickenpox in the military population have significantly declined since the introduction of the vaccine to the civilian population in Israel and almost disappeared completely since 2008 as the vaccine was included in the state-funded routine childhood immunization schedule. These findings underscore the need for a strong surveillance system and will aid in determing vaccination policies.

Seroprevalence of measles, mumps, rubella, varicella-zoster and hepatitis A-C in Emirati medical students.

PubMed

Sheek-Hussein, Mohamud; Hashmey, Rayhan; Alsuwaidi, Ahmed R; Al Maskari, Fatima; Amiri, Leena; Souid, Abdul-Kader

2012-12-05

The aims of this study were to assess the seroprevalence of vaccine-preventable infections in Emirati medical students, and to provide scientific evidence for implementation of a cost-effective immunization guideline and policy for medical school admission. This prospective cohort study involved 261 (61% female) Emirati medical students (preclinical and clinical) attending the College of Medicine and Health Sciences at UAE University. Data on vaccination and history of infectious diseases were collected from participants. Blood samples were collected between July 1, 2011 and May 30, 2012 for serological testing and QuantiFERON®-TB assay. All students tested negative for infection with hepatitis C virus and human immunodeficiency virus. The prevalence of seropositivity to rubella virus was 97%, varicella-zoster virus 88%, mumps virus 84%, measles virus 54%, hepatitis B virus (HBV) 48%, and hepatitis A virus 21%. The QuantiFERON®-TB test was positive in 8% and indeterminate in 2%. Forty percent of students received HBV vaccine at birth; their HBV titers (mean ± SD) were 17.2 ± 62.9 mIU/mL (median = 1.64). The remaining 60% received it at school and their titers were 293.4 ± 371.0 mIU/mL (median = 107.7, p = 0.000). About 50% of students were susceptible to HBV and measles virus; therefore, pre-matriculation screening for antibodies against these viruses is highly recommended. Moreover, tuberculosis screening is necessary because of the high influx of expatriates from endemic areas. Students with inadequate protection should be reimmunized prior to contact with patients.

Herpes Zoster Vaccination: Controversies and Common Clinical Questions.

PubMed

Van Epps, Puja; Schmader, Kenneth E; Canaday, David H

2016-01-01

Herpes zoster, clinically referred to as shingles, is an acute, cutaneous viral infection caused by reactivation of the varicella zoster virus, the same virus that causes chickenpox. The incidence of herpes zoster and its complications increase with decline in cell-mediated immunity, including age-associated decline. The most effective management strategy for herpes zoster is prevention of the disease through vaccination in those who are most vulnerable. Despite the demonstrated efficacy in reducing the incidence and severity of herpes zoster, the uptake of vaccine remains low. Here, we will discuss the controversies that surround the live herpes zoster vaccine and address the common clinical questions that arise. We will also discuss the new adjuvanted herpes zoster vaccine currently under investigation. © 2015 S. Karger AG, Basel.

Outer nuclear membrane fusion of adjacent nuclei in varicella-zoster virus-induced syncytia.

PubMed

Wang, Wei; Yang, Lianwei; Huang, Xiumin; Fu, Wenkun; Pan, Dequan; Cai, Linli; Ye, Jianghui; Liu, Jian; Xia, Ningshao; Cheng, Tong; Zhu, Hua

2017-12-01

Syncytia formation has been considered important for cell-to-cell spread and pathogenesis of many viruses. As a syncytium forms, individual nuclei often congregate together, allowing close contact of nuclear membranes and possibly fusion to occur. However, there is currently no reported evidence of nuclear membrane fusion between adjacent nuclei in wild-type virus-induced syncytia. Varicella-zoster virus (VZV) is one typical syncytia-inducing virus that causes chickenpox and shingles in humans. Here, we report, for the first time, an interesting observation of apparent fusion of the outer nuclear membranes from juxtaposed nuclei that comprise VZV syncytia both in ARPE-19 human epithelial cells in vitro and in human skin xenografts in the SCID-hu mouse model in vivo. This work reveals a novel aspect of VZV-related cytopathic effect in the context of multinucleated syncytia. Additionally, the information provided by this study could be helpful for future studies on interactions of viruses with host cell nuclei. Copyright © 2017 Elsevier Inc. All rights reserved.

Inactivated varicella zoster vaccine in autologous haemopoietic stem-cell transplant recipients: an international, multicentre, randomised, double-blind, placebo-controlled trial.

PubMed

Winston, Drew J; Mullane, Kathleen M; Cornely, Oliver A; Boeckh, Michael J; Brown, Janice Wes; Pergam, Steven A; Trociukas, Igoris; Žák, Pavel; Craig, Michael D; Papanicolaou, Genovefa A; Velez, Juan D; Panse, Jens; Hurtado, Kimberly; Fernsler, Doreen A; Stek, Jon E; Pang, Lei; Su, Shu-Chih; Zhao, Yanli; Chan, Ivan S F; Kaplan, Susan S; Parrino, Janie; Lee, Ingi; Popmihajlov, Zoran; Annunziato, Paula W; Arvin, Ann

2018-05-26

Recipients of autologous haemopoietic stem-cell transplants (auto-HSCT) have an increased risk of herpes zoster and herpes zoster-related complications. The aim of this study was to establish the efficacy and safety of an inactivated varicella zoster vaccine for the prevention of herpes zoster after auto-HSCT. In this randomised, double-blind, placebo-controlled phase 3 trial, participants were recruited from 135 medical centres (ie, stem-cell transplant centres and hospitals) in North America, South America, Europe, and Asia. Patients were eligible if they were aged 18 years or older, scheduled to receive an auto-HSCT within 60 days of enrolment, and had a history of varicella infection or were seropositive for antibodies to varicella zoster virus, or both. Exclusion criteria included a history of herpes zoster within the previous year of enrolment, and intended antiviral prophylaxis for longer than 6 months after transplantation. Participants were randomly assigned according to a central randomisation schedule generated by the trial statistician, to receive either the inactivated-virus vaccine from one of three consistency lots, a high-antigen lot, or placebo, stratified by age (<50 vs ≥50 years) and intended duration of antiviral prophylaxis after transplantation (≤3 months vs >3 to ≤6 months). Participants, investigators, trial staff, and the funder's clinical and laboratory personnel were masked to group assignment. Participants were given four doses of inactivated vaccine or placebo, with the first dose 5-60 days before auto-HSCT, and the second, third, and fourth doses at about 30, 60, and 90 days after transplantation. The primary efficacy endpoint was the incidence of herpes zoster, confirmed by PCR or adjudication by a masked clinical committee, or both, assessed in all participants randomly assigned to the vaccine consistency lot group or placebo group who received at least one dose of vaccine and had auto-HSCT. Safety was assessed in all

Clinical and immunologic features of recurrent herpes zoster (HZ).

PubMed

Nakamura, Yuki; Miyagawa, Fumi; Okazaki, Aiko; Okuno, Yoshinobu; Mori, Yasuko; Iso, Hiroyasu; Yamanishi, Koichi; Asada, Hideo

2016-11-01

Recurrent herpes zoster (HZ) is thought to be rare, but there have been few large-scale studies of recurrent HZ. We conducted a large-scale prospective cohort study to characterize recurrent HZ. We examined 12,522 participants aged 50 years or older in Shozu County and followed them up for 3 years. We compared the incidence of HZ and postherpetic neuralgia, severity of skin lesions and acute pain, cell-mediated immunity, and varicella-zoster virus-specific antibody titer between primary and recurrent HZ. A total of 401 participants developed HZ: 341 with primary HZ and 60 with recurrent HZ. Skin lesions and acute pain were significantly milder and the incidence of postherpetic neuralgia was lower in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Varicella-zoster virus skin test induced a stronger reaction in patients aged 50 to 79 years with recurrent HZ than in those with primary HZ. Information on previous HZ episodes was self-reported by participants, so it could not be confirmed that they actually had a history of HZ. Recurrent HZ was associated with milder clinical symptoms than primary HZ, probably because of stronger varicella-zoster virus-specific cell-mediated immunity in the patients with recurrence. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Three-Dimensional Normal Human Neutral Progenitor Tissue-Like Assemblies: A Model for Persistent Varicella-Zoster Virus Infection and Platform to Study Oxidate Stress and Damage in Multiple Hit Scenarios

NASA Technical Reports Server (NTRS)

Goodwin, Thomas J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpes virus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex three-dimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6]. By combining the RFs of microgravity, radiation, and viral infection we will demonstrate that living in the space environment leads to significant physiological consequences for the peripheral and subsequently the central nervous system (PNS, CNS) associated with OSaD generation and consequentially endangers long-duration and exploration-class missions.

Vaccine-strain herpes zoster found in the trigeminal nerve area in a healthy child: A case report.

PubMed

Iwasaki, Sayaka; Motokura, Kouji; Honda, Yoshitaka; Mikami, Masamitsu; Hata, Daisuke; Hata, Atsuko

2016-12-01

A previously healthy 2-year-old girl, vaccinated for varicella at 17 months, was admitted because of left-sided facial herpes zoster caused by vaccine-strain varicella-zoster virus (VZV). She recovered fully with no complication after intravenous treatment using acyclovir. Earlier reports have described that herpes zoster (HZ) rashes caused by vaccine-strain VZV tend to occur on the dermis corresponding to the skin area where the varicella vaccine was received. However, rashes appeared on this girl only in the trigeminal nerve area, which is unrelated to the vaccinated site. Results underscore the importance of distinguishing vaccine-strain VZV from wild-type VZV whenever encountering HZ cases after vaccination, even in immunocompetent children, irrespective of the skin lesion site. Monitoring vaccine-strain HZ incidence rates is expected to elucidate many aspects of varicella vaccine safety. Copyright © 2016 Elsevier B.V. All rights reserved.

Varicella zoster virus in the temporal artery of a patient with giant cell arteritis.

PubMed

Nagel, Maria A; Khmeleva, Nelly; Boyer, Philip J; Choe, Alexander; Bert, Robert; Gilden, Don

2013-12-15

We recently detected varicella zoster virus (VZV) in the temporal arteries (TA) of 5/24 patients with clinically suspect giant cell arteritis (GCA) whose TAs were GCA-negative pathologically; in those GCA-negative, VZV+TAs, virus antigen predominated in the arterial adventitia, but without medial necrosis and multinucleated giant cells. During our continuing search for VZV antigen in GCA-negative TAs, in the TA of one subject, we found abundant VZV antigen, as well as VZV DNA, in multiple regions (skip areas) of the TA spanning 350 μm, as well as in skeletal muscle adjacent to the infected TA. Additional pathological analysis of sections adjacent to those containing viral antigen revealed inflammation involving the arterial media and abundant multinucleated giant cells characteristic of GCA. Detection of VZV in areas of the TA with pathological features of GCA warrants further correlative pathological-virological analysis of VZV in GCA. © 2013.

Varicella-Zoster-Mediated Radiculitis Reactivation following Cervical Spine Surgery: Case Report and Review of the Literature

PubMed Central

Drazin, Doniel; Hanna, George; Shweikeh, Faris; Jeswani, Sunil; Lovely, Leah; Sokolov, Richard; Liu, John C.

2013-01-01

Varicella-zoster virus and herpes simplex virus types 1 and 2 are neurotropic viruses that can be reactivated after a surgical or stressful intervention. Although such cases are uncommon, consequences can be debilitating, and variable treatment responses merit consideration. We describe a 41-year-old male with a history of varicella-mediated skin eruptions, who presented with continuing right arm pain, burning, and numbness in a C6 dermatomal distribution following a C5-6 anterior cervical discectomy and fusion and epidural steroid injections. The operative course was uncomplicated and he was discharged home on postoperative day 1. Approximately ten days after surgery, the patient presented to the emergency department complaining of severe pain in his right upper extremity and a vesicular rash from his elbow to his second digit. He was started on Acyclovir and discharged home. On outpatient follow-up, his rash had resolved though his pain continued. The patient was started on a neuromodulating agent for chronic pain. This case adds to the limited literature regarding this rare complication, brings attention to the symptoms for proper diagnosis and treatment, and emphasizes the importance of prompt antiviral therapy. We suggest adding a neuromodulating agent to prevent long-term sequelae and resolve acute symptoms. PMID:24251050

Safety and immunogenicity of an AS01-adjuvanted varicella-zoster virus subunit candidate vaccine against herpes zoster in adults >=50 years of age.

PubMed

Chlibek, Roman; Bayas, José M; Collins, Harry; de la Pinta, Maria Luisa Rodriguez; Ledent, Edouard; Mols, Johann F; Heineman, Thomas C

2013-12-15

An adjuvanted varicella-zoster virus glycoprotein E (gE) subunit vaccine candidate for herpes zoster is in development. In this trial we compared the safety, reactogenicity, and immunogenicity of the vaccine antigen combined with different adjuvant doses. This was a phase II, observer-blind, randomized, multinational study. Adults ≥50 years old were randomized 4:4:2:1 to be vaccinated at months 0 and 2 with gE combined with a higher (AS01B) or lower (AS01E) dose adjuvant, unadjuvanted gE, or saline. Following each dose, solicited events were recorded for 7 days and unsolicited adverse events for 30 days. Serious adverse events were collected for 1 year. Cell-mediated and humoral immune responses were assessed at baseline and following each dose. No vaccine-related severe adverse events were reported. Solicited adverse events were generally mild to moderate and transient. For all gE-based vaccines, pain was the most common local symptom and fatigue the most common general symptom. Immune responses were significantly enhanced by AS01B and AS01E compared to unadjuvanted gE and were significantly stronger for gE/AS01B than for gE/AS01E. AS01 improved the immunogenicity of gE while retaining acceptable safety and reactogenicity profiles. The enhancement of gE-specific cellular and humoral responses was adjuvant dose dependent. NCT00802464.

[Herpes zoster of the trigeminal nerve: a case report and review of the literature].

PubMed

Carbone, V; Leonardi, A; Pavese, M; Raviola, E; Giordano, M

2004-01-01

Herpes zoster (shingles) is caused when the varicella zoster virus that has remained latent since an earlier varicella infection (chicken-pox) is reactivated. Herpes Zoster is a less common and endemic disease than varicella: factors causing reactivation are still not well known, but it occurs in older and/or immunocompromised individuals. Following reactivation, centrifugal migration of herpes zoster virus (HZV) occurs along sensory nerves to produce a characteristic painful cutaneous or mucocutaneous vesicular eruption that is generally limited to the single affected dermatome. Herpes zoster may affect any sensory ganglia and its cutaneous nerve: the most common sites affected are thoracic dermatomes (56%), followed by cranial nerves (13%) and lumbar (13%), cervical (11%) and sacral nerves (4%). Among cranial nerves, the trigeminal and facial nerves are the most affected due to reactivation of HZV latent in gasserian and geniculated ganglia. The 1st division of the trigeminal nerve is commonly affected, whereas the 2nd and the 3rd are rarely involved. During the prodromal stage, the only presenting symptom may be odontalgia, which may prove to be a diagnostic challenge for the dentist, since many diseases can cause orofacial pain, and the diagnosis must be established before final treatment. A literature review of herpes zoster of the trigeminal nerve is presented and the clinical presentation, differential diagnosis and treatment modalities are underlined. A case report is presented.

A pseudoreceptor modelling study of the varicella-zoster virus and human thymidine kinase binding sites

NASA Astrophysics Data System (ADS)

Greenidge, Paulette A.; Merz, Alfred; Folkers, Gerd

1995-12-01

A representative range of pyrimidine nucleoside analogues that are known to inhibit herpes simplex virus (HSV) replication have been used to construct receptor binding site models for the varicella-zoster virus (VZV), thymidine kinase (TK) and human TK1. Given a set of interacting ligands, superimposed in such a manner as to define a pharmacophore, the pseudoreceptor modelling technique Yak provides a means of building binding site models of macromolecules for which no three-dimensional experimental structures are available. Once the models have been evaluated by their ability to reproduce experimental binding data [Vedani et al., J. Am. Chem. Soc., 117 (1995) 4987], they can be used for predictive purposes. Calculated and experimental values of relative binding affinity are compared. Our models suggest that the substitution of one residue may be sufficient to determine ligand subtype affinity.

Secular trends of chickenpox among military population in Israel in relation to introduction of varicella zoster vaccine 1979–2010

PubMed Central

Mimouni, Daniel; Levine, Hagai; Tzurel Ferber, Anat; Rajuan-Galor, Inbal; Huerta-Hartal, Michael

2013-01-01

Chickenpox is a contagious disease caused by the varicella zoster virus. There is scarce data on long-term trends of chickenpox and its relation to vaccinations practices. We aimed to evaluate trends of chickenpox in a military population during the period 1979–2010 and to assess temporal associations in relation with the introduction of varicella zoster vaccine to the civilian population in Israel in 2000. The archives of the Epidemiology Section of the Israel Defense Forces, where chickenpox is a notifiable disease, were reviewed for all cases of chickenpox from January 1, 1979–December 31, 2010. Annual and monthly incidence rates were calculated and analyzed in relation to vaccine introduction. Between 1979–2000, incidence rates fluctuated around 10 cases per 10,000 soldiers without a clear trend. Since 2000 there has been a dramatic 10-fold decline in incidence, especially notable since 2008, from eight per 10,000 soldiers in 2000 to the lowest rate ever recorded, in 2009, of 0.57 cases per 10,000 soldiers. A seasonal sinusoidal pattern was clearly demonstrated, with rising incidence from November to May followed by a gradual decline to October. The results of this long-term study suggest that the rates of chickenpox in the military population have significantly declined since the introduction of the vaccine to the civilian population in Israel and almost disappeared completely since 2008 as the vaccine was included in the state-funded routine childhood immunization schedule. These findings underscore the need for a strong surveillance system and will aid in determing vaccination policies. PMID:23412473

Incidence and case-fatality of varicella-zoster virus infection among pediatric cancer patients in developing countries.

PubMed

Ojha, Rohit P; Stallings-Smith, Sericea; Aviles-Robles, Martha J; Gomez, Sergio; Somarriba, María Mercedes; Caniza, Miguela A

2016-04-01

Limited evidence is available about varicella-zoster virus (VZV) infection among pediatric cancer patients in developing countries, which raises questions about the generalizability of VZV vaccine recommendations for pediatric cancer patients (derived from developed countries) to these settings. We assessed the incidence and case-fatality of VZV infection at three institutions in developing countries (Argentina, Mexico, and Nicaragua). Individuals eligible for our study were aged <20 years and actively receiving cancer-directed therapy. We estimated a summary incidence rate (IR) and case-fatality risk with corresponding 95 % confidence limits (CL) of VZV infection across sites using random-effects models. Our study population comprised 511 pediatric cancer patients, of whom 64 % were aged <10 years, 58 % were male, and 58 % were diagnosed with leukemia. We observed a total of 10 infections during 44,401 person-days of follow-up across the 3 sites (IR = 2.3, 95 % CL 1.2, 4.2). The summary case-fatality risk was 10 % (95 % CL 1.4, 47 %) based on one death. Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. VZV vaccine recommendations for pediatric cancer patients in developed countries may be generalizable to developing countries. • Current recommendations, based on evidence from pediatric cancer patients in developed countries, contraindicate varicella-zoster virus (VZV) vaccination until completion of cancer-directed therapy and recovery of immune function. • The generalizability of these VZV vaccine recommendations to pediatric cancer patients in developing countries is unknown because of limited information about the incidence and case-fatality of VZV in these settings. What is New: • Our results suggest low incidence and case-fatality of VZV infections among pediatric cancer patients in three developing countries. • VZV vaccine recommendations based on evidence from

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus.

PubMed

Hur, Jian

2015-06-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention.

Seroepidemiology of varicella among elementary school children in northern Taiwan.

PubMed

Lin, Ming-Ru; Kuo, Ching-Chia; Hsieh, Yu-Chia; Huang, Ya-Ling; Huang, Yu-Chiau; Hung, Yung-Tai; Huang, Yhu-Chering

2017-06-01

In Taiwan, varicella vaccine was included in the expanded program of immunization since 2004. A seroepidemiologic study in the postvaccine era is helpful to evaluate the efficiency of current varicella vaccination strategies. We used a multistage stratified systematic sampling design to classify 29 administrative districts of New Taipei City into five strata. In 2013, a total of 936 students from 14 primary schools were recruited and had blood drawn for serology tests for varicella-zoster virus-immunoglobulin-G via indirect chemiluminescence immunoassays. A history of clinical varicella and information on varicella vaccination status were obtained. Overall, the seroprevalence was 64.1%. For the five strata, the seropositive rate ranged from 54.2% (Stratum 5) to 71.7% (Stratum 2) with no significant difference. For each participating school, the seropositive rate ranged from 44.4% to 72.9% with a statistically significant difference (p < 0.005). For school children in each grade, seropositive rate increased significantly from 53.2% for Grade 1 to 71.8% for Grade 3 (p = 0.005) and increased steadily from 61.2% for Grade 4 to 71.2% for Grade 6 (p = 0.17). A positive correlation was observed between the seropositive rate and geometric mean titers (p = 0.035). Geometric mean titers and the rate of a history of clinical varicella were positively correlated with increasing class grades. Nine years after the introduction of the varicella vaccine into the expanded program of immunization in Taiwan, around two-thirds of elementary schoolchildren were seropositive for varicella-zoster virus. Further surveillance studies on clinical varicella cases are worthwhile to determine whether a second dose of varicella vaccine is needed in Taiwan. Copyright © 2015. Published by Elsevier B.V.

Varicella outbreak in Sudanese refugees from Calais.

PubMed

Lesens, O; Baud, O; Henquell, C; Lhermet Nurse, A; Beytout, J

2016-05-01

We describe an outbreak of varicella in 31 Sudanese refugees (all except one were male, mean age: 26 ± 1), from the Calais migrant camp and sheltered in a French transit area. The attack rate was 39%. Adults are scantly immunized against varicella zoster virus in East Africa and may be exposed to epidemics once in France. © International Society of Travel Medicine, 2016. All rights reserved. Published by Oxford University Press. For permissions, please e-mail: journals.permissions@oup.com.

Detection of varicella-zoster virus antigens in lesional skin of zosteriform lichen planus but not in that of linear lichen planus.

PubMed

Mizukawa, Y; Horie, C; Yamazaki, Y; Shiohara, T

2012-01-01

Distinctions between 'linear lichen planus' (LP) and 'zosteriform LP' are difficult to determine solely based on clinical findings. The aim of this study is to determine whether the presence of the varicella-zoster virus (VZV) antigens could be used to differentiate the zosteriform LP from the linear LP. We immunohistochemically investigated the presence of in vivo localization of VZV antigens in 8 LP lesions (zosteriform LP: n = 5, linear LP: n = 3). We describe 2 cases of zosteriform LP without apparent prior episodes of herpes zoster, in whom VZV antigens were detected in the eccrine epithelium. Further analysis showed that VZV antigens were exclusively detected in the eccrine epithelium in the zosteriform LP lesions, but not in the linear LP lesions. Etiological differences exist between zosteriform LP and linear LP. The presence of VZV antigens in lesional skin of the former indicates a possible triggering role of this virus in the pathogenesis of this variant. Copyright © 2012 S. Karger AG, Basel.

Sacral herpes-zoster infection presenting as sciatic pain.

PubMed

Ablin, J; Symon, Z; Mevorach, D

1996-06-01

Acute herpes-zoster infection is a painful dermatomal lesion that can be manifested by a wide array of neurologic symptoms. We present a 55-year-old female with non-Hodgkin's lymphoma, who developed a left sciatic pain involving the S roots. Two weeks later, the patient developed fever and vesicular rash over the left gluteal area. Herpes-zoster infection was diagnosed and confirmed by the presence of immunoglobulin M (IgM) antibodies against varicella-zoster. The pain and rash resolved, after treatment with acyclovir. In the appropriate clinical setting, sacral herpes-zoster infection ought to be considered in the differential diagnosis of new-onset sciatic pain.

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation.

PubMed

Kennedy, Peter G E; Rovnak, Joel; Badani, Hussain; Cohrs, Randall J

2015-07-01

Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an 'end-less' state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is increasing

Sacral Herpes Zoster Associated with Voiding Dysfunction in a Young Patient with Scrub Typhus

PubMed Central

2015-01-01

When a patient presents with acute voiding dysfunction without a typical skin rash, it may be difficult to make a diagnosis of herpes zoster. Here, we present a case of scrub typhus in a 25-year-old man with the complication of urinary dysfunction. The patient complained of loss of urinary voiding sensation and constipation. After eight days, he had typical herpes zoster eruptions on the sacral dermatomes and hypalgesia of the S1-S5 dermatomes. No cases of dual infection with varicella zoster virus and Orientia tsutsugamushi were found in the literature. In the described case, scrub typhus probably induced sufficient stress to reactivate the varicella zoster virus. Early recognition of this problem is imperative for prompt and appropriate management, as misdiagnosis can lead to long-term urinary dysfunction. It is important that a diagnosis of herpes zoster be considered, especially in patients with sudden onset urinary retention. PMID:26157595

Susceptibility to measles, rubella, mumps, and varicella-zoster viruses among healthcare workers.

PubMed

Aypak, Cenk; Bayram, Yasemin; Eren, Hayriye; Altunsoy, Adalet; Berktaş, Mustafa

2012-01-01

It is important to identify and immunize susceptible healthcare workers to prevent and control hospital infections. Our aim was to evaluate the specific antibodies against the measles, mumps, and rubella viruses and the varicella zoster virus among healthcare workers in a tertiary-care hospital. A total of 284 healthcare workers (89 men and 195 women; mean age, 33.5 ± 11 years), including 111 nurses, 87 physicians, 34 laboratory technicians, and 52 members of the housekeeping staff, of Van Training and Research Hospital were enrolled in this study. Antibodies were detected with an enzyme-linked immunosorbent assay. The numbers of workers with serological susceptibility to mumps, measles, rubella, or chicken pox were 26 (9.2%), 18 (6.3%), 7 (2.5%), and 5 (1.8%), respectively. Although the difference was not statistical significant, the rate of seroprevalence of antibodies was lowest for measles (90.8%; p>0.05). Susceptibility to measles, mumps, and rubella, and chicken pox was more prevalent among young healthcare workers (p<0.001). Not all healthcare workers born before 1957 were immune to these vaccine-preventable diseases. These data confirm that screening and vaccination of susceptible healthcare workers is essential regardless of age.

[Four cases of urinary dysfunction associated with sacral herpes zoster].

PubMed

Matsuo, Tomohiro; Oba, Kojiro; Miyata, Yasuyoshi; Igawa, Tsukasa; Sakai, Hideki

2014-02-01

Herpes zoster is caused by the infection of Varicella-Zoster virus. The anatomical distribution of herpes zoster in the sacral area is only 6. 9%1). Moreover, the onset rate of herpes zoster with urinary dysfunction is 0.6%1). The lesion sites of herpes zoster which cause urinary dysfunction are almost lumber and sacral areas. We describe four cases of sacral herpes zoster with urinary dysfunction in this report. All patients were elderly people (66-84 years old), and all patients were administered anti-virus drugs and alpha 1-adrenergic receptor blockers. Because of urinary retention, three patients have performed clean intermittent self-catheterization (CIC) for several weeks. As the lesions of herpes zoster healed, each patient recovered from urinary dysfunction.

Varicella Pneumonia Complicating Pregnancy: A Report of Seven Cases

PubMed Central

Schutte, Teresa J.; Rogers, Louise C.

1996-01-01

Background: Pneumonia is the most common complication of varicella-zoster infection in adults and has potentially devastating effects when complicating pregnancy. Due to the significant morbidity and mortality associated with this complication during pregnancy and the small number of reported cases in the literature, we present this report to help educate physicians who care for pregnant women. Cases: Seven patients are presented in this report. These patients presented at various stages in pregnancy, from 17 to 31 weeks of gestation. Three of the patients had unremarkable hospital courses. Three of the patients had hospital stays over 21 days in duration. One patient died from complications of varicella pneumonia after 31 days of hospitalization. The obstetric outcomes of the 7 patients described include 1 non-viable delivery at 20 weeks gestation, 3 term deliveries, 2 preterm deliveries, and 1 patient who has not yet delivered. All of the patients presented were treated with intravenous acyclovir therapy. Of the patients described, 3 required intubation and ventilatory support. Other complications encountered include disseminated intravascular coagulation (DIC), adult respiratory distress syndrome (ARDS), metabolic encephalopathy, pneumothorax, superimposed bacterial pneumonia, and sepsis. Conclusion: The course and treatment of varicella pneumonia complicating pregnancy are discussed. Current recommendations regarding the use of varicella-zoster immune globulin (VZIG) are also reviewed. PMID:18476122

Herpes zoster: A clinicocytopathological insight.

PubMed

Shah, Snehal; Singaraju, Sasidhar; Einstein, A; Sharma, Ashish

2016-01-01

Herpes zoster or shingles is reactivation of the varicella zoster virus that had entered the cutaneous nerve endings during an earlier episode of chicken pox traveled to the dorsal root ganglia and remained in a latent form. This condition is characterized by occurrence of multiple, painful, unilateral vesicles and ulceration which shows a typical single dermatome involvement. In this case report, we present a patient with herpes zoster involving the mandibular division of the trigeminal nerve, with unilateral vesicles over the right side of lower third of face along the trigeminal nerve tract, with intraoral involvement of buccal mucosa, labial mucosa and the tongue of the same side. Cytopathology revealed classic features of herpes infection including inclusion bodies, perinuclear halo and multinucleated cells.

Management of varicella zoster virus retinitis in AIDS

PubMed Central

Moorthy, R.; Weinberg, D.; Teich, S.; Berger, B.; Minturn, J.; Kumar, S.; Rao, N.; Fowell, S.; Loose, I.; Jampol, L.

1997-01-01

AIMS/BACKGROUND—Varicella zoster virus retinitis (VZVR) in patients with AIDS, also called progressive outer retinal necrosis (PORN), is a necrotising viral retinitis which has resulted in blindness in most patients. The purposes of this study were to investigate the clinical course and visual outcome, and to determine if the choice of a systemic antiviral therapy affected the final visual outcome in patients with VZVR and AIDS.
METHODS—A review of the clinical records of 20 patients with VZVR from six centres was performed. Analysis of the clinical characteristics at presentation was performed. Kruskall-Wallis non-parametric one way analysis of variance (KWAOV) of the final visual acuities of patients treated with acyclovir, ganciclovir, foscarnet, or a combination of foscarnet and ganciclovir was carried out.
RESULTS—Median follow up was 6 months (range 1.3-26 months). On presentation, 14 of 20 patients (70%) had bilateral disease, and 75% (15 of 20 patients) had previous or concurrent extraocular manifestations of VZV infection. Median initial and final visual acuities were 20/40 and hand movements, respectively. Of 39 eyes involved, 19 eyes (49%) were no light perception at last follow up; 27 eyes (69%) developed rhegmatogenous retinal detachments. Patients treated with combination ganciclovir and foscarnet therapy or ganciclovir alone had significantly better final visual acuity than those treated with either acyclovir or foscarnet (KWAOV: p = 0.0051).
CONCLUSIONS—This study represents the second largest series, the longest follow up, and the first analysis of visual outcomes based on medical therapy for AIDS patients with VZVR. Aggressive medical treatment with appropriate systemic antivirals may improve long term visual outcome in patients with VZVR. Acyclovir appears to be relatively ineffective in treating this disease.

 PMID:9135381

A 70-year-old woman with shingles: review of herpes zoster.

PubMed

Whitley, Richard J

2009-07-01

Herpes zoster is a common late complication of varicella-zoster virus exposure and can be further complicated by postherpetic neuralgia. Ms A is a 70-year-old woman with shingles and Ramsay-Hunt syndrome who presented to the emergency department with a few days of earache followed by pain in the back of her head. Using her case as a springboard, the diagnosis, natural history, and treatment of herpes zoster and postherpetic neuralgia in immunocompetent older adults are reviewed, in addition to the effectiveness of the herpes zoster vaccine.

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62.

PubMed

Kim, Seong K; Shakya, Akhalesh K; Kim, Seongman; O'Callaghan, Dennis J

2016-01-15

The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62, EHV-1 IEP, and HSV

Functional Characterization of the Serine-Rich Tract of Varicella-Zoster Virus IE62

PubMed Central

Shakya, Akhalesh K.; Kim, Seongman; O'Callaghan, Dennis J.

2015-01-01

ABSTRACT The immediate early 62 protein (IE62) of varicella-zoster virus (VZV), a major viral trans-activator, initiates the virus life cycle and is a key component of pathogenesis. The IE62 possesses several domains essential for trans-activation, including an acidic trans-activation domain (TAD), a serine-rich tract (SRT), and binding domains for USF, TFIIB, and TATA box binding protein (TBP). Transient-transfection assays showed that the VZV IE62 lacking the SRT trans-activated the early VZV ORF61 promoter at only 16% of the level of the full-length IE62. When the SRT of IE62 was replaced with the SRT of equine herpesvirus 1 (EHV-1) IEP, its trans-activation activity was completely restored. Herpes simplex virus 1 (HSV-1) ICP4 that lacks a TAD very weakly (1.5-fold) trans-activated the ORF61 promoter. An IE62 TAD-ICP4 chimeric protein exhibited trans-activation ability (10.2-fold), indicating that the IE62 TAD functions with the SRT of HSV-1 ICP4 to trans-activate viral promoters. When the serine and acidic residues of the SRT were replaced with Ala, Leu, and Gly, trans-activation activities of the modified IE62 proteins IE62-SRTΔSe and IE62-SRTΔAc were reduced to 46% and 29% of wild-type activity, respectively. Bimolecular complementation assays showed that the TAD of IE62, EHV-1 IEP, and HSV-1 VP16 interacted with Mediator 25 in human melanoma MeWo cells. The SRT of IE62 interacted with the nucleolar-ribosomal protein EAP, which resulted in the formation of globular structures within the nucleus. These results suggest that the SRT plays an important role in VZV viral gene expression and replication. IMPORTANCE The immediate early 62 protein (IE62) of varicella-zoster virus (VZV) is a major viral trans-activator and is essential for viral growth. Our data show that the serine-rich tract (SRT) of VZV IE62, which is well conserved within the alphaherpesviruses, is needed for trans-activation mediated by the acidic trans-activation domain (TAD). The TADs of IE62

[Seroprevalence of rubella virus, varicella zoster virus, cytomegalovirus and parvovirus B19 among pregnant women in the Sousse region, Tunisia].

PubMed

Hannachi, N; Marzouk, M; Harrabi, I; Ferjani, A; Ksouri, Z; Ghannem, H; Khairi, H; Hidar, S; Boukadida, J

2011-02-01

The aim of the study is to evaluate seroprevalence of rubella virus (RV), cytomegalovirus (CMV), varicella zoster virus (VZV), and parvovirus B19 (PB19) in 404 Tunisian pregnant women, and to determine reliability of maternal past history of eruption. Sociodemographic characteristics, risk factors, and past history of eruption were collected through a questionnaire. Serologic tests were performed using enzyme immunoassays. Risk factors were analyzed using univariate and multivariate logistic regression models. Seroprevalences were 79.7% for rubella, 96.3% for CMV, 80.9% for VZV, and 76.2% for PB19. In multivariate analysis, the number of persons per room (> 2) in the house during childhood was associated with CMV infection (P = 0.004), irregular professional husband's activity was correlated with VZV infection (P = 0.04), and an age of more than 30 years was associated with PB19 infection (P = 0.02). History of rubella, varicella, and PB19 infection was unknown for, respectively, 55.8%, 20%, and 100% of women. False history of rubella and varicella were found for 7.4% and 15% of women, respectively. The positive and negative predictive values (PPV and NPV) of rubella history were, respectively, 92.6% and 17.2%, and were, respectively, 84.9% and 20.9% for varicella history. Susceptibility to RV, VZV, and PB19 infection remains high in pregnancy in our population. Preventive strategies against congenital rubella must be reinforced. Vaccination against VZV should be considered in seronegative women. Systemic CMV screening is not warranted in our country where high immunity is acquired probably in childhood. Since maternal history of eruption is not reliable, we recommend serologic testing to determine immune status of women.

Progressive outer retinal necrosis (PORN) in AIDS patients: a different appearance of varicella-zoster retinitis.

PubMed

Pavesio, C E; Mitchell, S M; Barton, K; Schwartz, S D; Towler, H M; Lightman, S

1995-01-01

Retinal infections caused by the varicella-zoster virus (VZV) have been reported in immunocompetent and immunocompromised individuals. Two cases of a VZV-related retinitis are described with the characteristic features of the recently described progressive outer retinal necrosis (PORN) syndrome. Both patients suffered from the acquired immunodeficiency syndrome (AIDS) with greatly reduced peripheral blood CD4+ T lymphocyte counts, and presented with macular retinitis without vitritis. The disease was bilateral in one case and unilateral in the other. The clinical course was rapidly progressive with widespread retinal involvement and the development of rhegmatogenous retinal detachment with complete loss of vision in the affected eyes despite intensive intravenous antiviral therapy. VZV DNA was identified in vitreous biopsies, by molecular techniques based on the polymerase chain reaction (PCR), in both patients. At present, the use of very high-dose intravenous acyclovir may be the best therapeutic option in these patients for whom the visual prognosis is poor. Intravitreal antiviral drugs could also contribute to the management of these cases.

A systematic review of the cost effectiveness of herpes zoster vaccination.

PubMed

Szucs, Thomas D; Pfeil, Alena M

2013-02-01

The varicella zoster virus (VZV) can cause two infections: chickenpox or herpes zoster (HZ). Whereas chickenpox infections are normally mild but common among children, HZ infections are common among elderly people and can give rise to post-herpetic neuralgia (PHN), a severe and painful complication. This review aimed to summarize the literature available on the cost effectiveness of HZ vaccination and to summarize key issues for decision makers to consider when deciding on the reimbursement of HZ vaccination. We conducted a literature search of the databases PubMed and EMBASE using EndNote X4 from Thomson Reuters. The following combinations of keywords were used: 'herpes zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'herpes zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation', 'varicella zoster vaccine' AND 'cost(-)effectiveness' or AND 'economic evaluation', and 'varicella zoster vaccination' AND 'cost(-)effectiveness' or AND 'economic evaluation'. A total of 11 studies were identified and included. Cost-effectiveness analyses of varicella zoster vaccination were excluded. The quality of the included studies ranged from 'moderate' to 'moderate to good' according to the British Medical Journal guidelines of Drummond and Jefferson and the Quality of Health Economic Studies (QHES) score of Ofman et al. Most studies evaluated the cost effectiveness of universal HZ vaccination in adults aged 50 years or 60 years and older. Data sources and model assumptions regarding epidemiology, utility estimates and costs varied between studies. All studies calculated costs per QALY, which allows comparing costs of interventions in different diseases. The costs per QALY gained and the incremental cost-effectiveness ratio (ICER) differed between studies depending on the age at vaccination, duration of vaccine efficacy, cost of vaccine course and economic perspective. All but one of the studies concluded that most vaccination

Serological Susceptibility to Varicella among U.S. Immigration and Customs Enforcement Detainees

PubMed Central

Varan, Aiden K.; Lederman, Edith R.; Stous, Shanon S.; Elson, Diana; Freiman, Jennifer L.; Marin, Mona; Lopez, Adriana S.; Stauffer, William M.; Joseph, Rachael H.; Waterman, Stephen H.

2018-01-01

U.S. Immigration and Customs Enforcement (ICE) is responsible for detaining unauthorized aliens during immigration proceedings. During 2014–2015, adult ICE detainees at a California facility were invited to complete a survey concerning self-reported varicella history and risk factors. Participants underwent serological testing for varicella-zoster virus (VZV) IgG; susceptible individuals were offered varicella vaccination. Among 400 detainees with available serology results, 48 (12%) were susceptible to varicella. Self-reported varicella history was negatively associated with susceptibility (adjusted odds ratio [aOR]=0.16; 95% CI=0.07, 0.35). Among 196 detainees reporting a positive history, 95% had VZV IgG levels suggestive of varicella immunity. Among 44 susceptible detainees offered vaccination, 86% accepted. Given relatively high varicella susceptibility, targeted screening and vaccination among ICE detainees lacking a positive history might reduce varicella transmission risks. PMID:28945148

Reactivation of Herpes Zoster Keratitis With Corneal Perforation After Zoster Vaccination.

PubMed

Jastrzebski, Andre; Brownstein, Seymour; Ziai, Setareh; Saleh, Solin; Lam, Kay; Jackson, W Bruce

2017-06-01

We present a case of reactivated herpes zoster keratouveitis of 6 years duration with corneal perforation requiring penetrating keratoplasty shortly after inoculation with herpes zoster vaccine (Zostavax, Merck, Quebec, Canada). Retrospective case report. A 67-year-old woman with a 5-year history of recurrent unilateral herpes zoster keratouveitis in her right eye presented with another recurrence 2 weeks after Zostavax vaccination. Three months later, she developed descemetocele and 2 months afterward, corneal perforation, which was managed by penetrating keratoplasty. Immunohistopathological examination disclosed positive staining for varicella zoster virus in most of the keratocytes adjacent to the descemetocele and perforation, most vividly in the deeper two-thirds of the stroma where the keratocytes were most dense, but not in corneal epithelium or endothelium. Electron microscopic examination showed universally severely degenerated corneal keratocytes in the corneal stroma adjacent to the perforation with variable numbers of herpes virus capsids present in half of these cells. Only a rare normal-appearing keratocyte was identified in the more peripheral corneal stroma. We present a case of reactivation of herpes keratouveitis shortly after vaccination with Zostavax in a patient with previous herpes zoster ophthalmicus. We demonstrate, for the first time, ultrastructural evidence consistent with inactive virus capsids in diffusely degenerated keratocytes in the extracted corneal tissue.

Incidence and use of resources for chickenpox and herpes zoster in Latin America and the Caribbean--a systematic review and meta-analysis.

PubMed

Bardach, Ariel; Cafferata, María Luisa; Klein, Karen; Cormick, Gabriela; Gibbons, Luz; Ruvinsky, Silvina

2012-12-01

Varicella-zoster virus causes chickenpox and herpes zoster. More than 90% of varicella cases occur in childhood. The aim of this study was to gather all relevant information on epidemiology and resource use in Latin America and the Caribbean since 2000. Epidemiologic studies published since 2000 with at least 50 cases of varicella or herpes zoster, or at least 10 cases of congenital disease were included. Gray literature was also searched. Outcomes included incidence, admission rate, mortality and case-fatality ratio. Use of resources and both direct and indirect costs associated were extracted. From the 495 records identified, 23 were included in the meta-analysis to report varicella-zoster virus outcomes and 3 in the herpes zoster analysis. The global pooled varicella incidence in subjects under 15 years of age was 42.9 cases per 1000 individuals per year (95% confidence interval: 26.9-58.9); children under 5 years of age were the most affected. Pooled general admission rate was 3.5 per 100,000 population (95% confidence interval: 2.9-4.1) and median hospitalization was 5-9 days. The most common varicella complications reported in studies were skin infections (3-61%), followed by respiratory infections (0-15%) and neurologic problems (1-5%). Direct costs averaged (2011/international dollar [I$]) $2040 per admission (range, I$ 298-5369) and I$70 per clinical visit (range, 11-188 I$). Limited information was available on the outcomes studied. Improvements in the surveillance of ambulatory cases are required to obtain a better epidemiologic picture. As of 2011, only 2 countries introduced the vaccine in national immunization programs in Latin America and the Caribbean.

Errant processing and structural alterations of genomes present in a varicella-zoster virus vaccine.

PubMed Central

Vlazny, D A; Hyman, R W

1985-01-01

Five minority populations of aberrant, varicella-zoster virus (VZV)-derived genomes were identified among the encapsidated DNAs obtained from the nuclear and cytoplasmic fractions of an in vitro infection initiated with a lyophilized sample of the BIKEN VZV vaccine (strain Oka). These were (i) VZV genomes, present within nuclear but not cytoplasmic viral capsids, which had been cleaved at a specific site within the short segment and which were, therefore, 3.15 megadaltons (approximately 4% of the VZV genome length) short of full length; (ii) highly deleted, repetitive VZV genomes which contained the errant cleavage site but not the usual VZV genome terminal sequences; (iii) VZV genomes into which multiples of 1 through 5 defective genome repeat units had been inserted into a homologous site; (iv) VZV genomes with additions of 0.1 or 0.18 megadaltons of DNA at both the terminal and internal ends of the short segment; and (v) VZV DNA which had lost the HindIII restriction site at map position 0.11. Images PMID:2993670

Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

PubMed

Hornberger, John; Robertus, Katherine

2006-09-05

The Shingles Prevention Study showed that a varicella-zoster virus (VZV) vaccine administered to adults 60 years of age or older reduced the incidence of herpes zoster from 11.12 to 5.42 cases per 1000 person-years. Median follow-up was 3.1 years, and relative risk reduction was 51.3% (95% CI, 44.2% to 57.6%). To assess the extent to which clinical and cost variables influence the cost-effectiveness of VZV vaccination for preventing herpes zoster in immunocompetent older adults. Decision theoretical model. English-language data published to March 2006 identified from MEDLINE on herpes zoster rates, vaccine effectiveness, quality of life, medical resource use, and unit costs. Immunocompetent adults 60 years of age or older with a history of VZV infection. Lifetime. U.S. societal. Varicella-zoster virus vaccination versus no vaccination. Incremental quality-adjusted survival and cost per quality-adjusted life-year (QALY) gained. By reducing incidence and severity of herpes zoster, vaccination can increase quality-adjusted survival by 0.6 day compared with no vaccination. One scenario in which vaccination costs less than 100,000 dollars per QALY gained is when 1) the unit cost of vaccination is less than 200 dollars, 2) the age at vaccination is less than 70 years, and 3) the duration of vaccine efficacy is more than 30 years. Vaccination would be more cost-effective in "younger" older adults (age 60 to 64 years) than in "older" older adults (age > or =80 years). Longer life expectancy and a higher level of vaccine efficacy offset a lower risk for herpes zoster in the younger group. Other factors influencing cost-effectiveness include quality-of-life adjustments for acute zoster, unit cost of the vaccine, risk for herpes zoster, and duration of vaccine efficacy. The effectiveness of VZV vaccination remains uncertain beyond the median 3.1-year duration of follow-up in the Shingles Prevention Study. Varicella-zoster virus vaccination to prevent herpes zoster in older

A comparison of herpes simplex virus type 1 and varicella-zoster virus latency and reactivation

PubMed Central

Kennedy, Peter G. E.; Rovnak, Joel; Badani, Hussain

2015-01-01

Herpes simplex virus type 1 (HSV-1; human herpesvirus 1) and varicella-zoster virus (VZV; human herpesvirus 3) are human neurotropic alphaherpesviruses that cause lifelong infections in ganglia. Following primary infection and establishment of latency, HSV-1 reactivation typically results in herpes labialis (cold sores), but can occur frequently elsewhere on the body at the site of primary infection (e.g. whitlow), particularly at the genitals. Rarely, HSV-1 reactivation can cause encephalitis; however, a third of the cases of HSV-1 encephalitis are associated with HSV-1 primary infection. Primary VZV infection causes varicella (chickenpox) following which latent virus may reactivate decades later to produce herpes zoster (shingles), as well as an increasingly recognized number of subacute, acute and chronic neurological conditions. Following primary infection, both viruses establish a latent infection in neuronal cells in human peripheral ganglia. However, the detailed mechanisms of viral latency and reactivation have yet to be unravelled. In both cases latent viral DNA exists in an ‘end-less’ state where the ends of the virus genome are joined to form structures consistent with unit length episomes and concatemers, from which viral gene transcription is restricted. In latently infected ganglia, the most abundantly detected HSV-1 RNAs are the spliced products originating from the primary latency associated transcript (LAT). This primary LAT is an 8.3 kb unstable transcript from which two stable (1.5 and 2.0 kb) introns are spliced. Transcripts mapping to 12 VZV genes have been detected in human ganglia removed at autopsy; however, it is difficult to ascribe these as transcripts present during latent infection as early-stage virus reactivation may have transpired in the post-mortem time period in the ganglia. Nonetheless, low-level transcription of VZV ORF63 has been repeatedly detected in multiple ganglia removed as close to death as possible. There is

Zoster vaccine (Zostavax): a review of its use in preventing herpes zoster and postherpetic neuralgia in older adults.

PubMed

Sanford, Mark; Keating, Gillian M

2010-02-01

Individuals who have been infected with varicella zoster virus (VZV) are at risk for developing herpes zoster and this risk appears to be related to a decline in VZV-specific cell-mediated immunity (CMI). Zostavax (zoster vaccine) is a one-dose, high-potency, live, attenuated VZV vaccine that boosts VZV-specific CMI and this is its presumed mechanism of action. Zoster vaccine is registered in the EU for use in adults aged >or=50 years for the prevention of herpes zoster and herpes zoster-related postherpetic neuralgia. In the Shingles Prevention Study, a placebo-controlled trial in adults aged >or=60 years (n = 38 546), zoster vaccine led to a sustained boost of VZV-specific CMI. Over a mean herpes zoster surveillance period of 3.1 years, zoster vaccine reduced the herpes zoster-related burden of illness by 61%, reduced the incidence of herpes zoster by 51% and reduced the incidence of postherpetic neuralgia by 67%. Zoster vaccine recipients who developed herpes zoster had a shorter illness duration and severity than placebo recipients who developed herpes zoster. Zoster vaccine had continuing efficacy in a Shingles Prevention Study subpopulation followed for 7 years post-vaccination. Zoster vaccine was generally well tolerated in older adults. While cost-effectiveness estimates in pharmacoeconomic analyses varied widely according to vaccine and herpes zoster parameter cost/benefit estimates, an analysis from a UK perspective found a zoster vaccine immunization programme in adults aged 65 years to be cost effective. In older adults, the zoster vaccine has the potential to significantly reduce the herpes zoster burden of illness by decreasing the incidence of herpes zoster or reducing its severity.

Herpes zoster as a cause of viral meningitis in immunocompetent patients.

PubMed

Kangath, Raghesh Varot; Lindeman, Tracey Einem; Brust, Karen

2013-01-09

A 30-year-old Caucasian woman, without significant medical history or immunosuppression, presented with a 7-day history of severe headache and neck pain. The patient was presumed to have tension headache versus migraine, but was admitted because her symptoms did not resolve. A lumbar puncture was performed showing lymphocytic pleocytosis suggestive of aseptic meningitis and the patient was started on broad-spectrum antibiotics and acyclovir. After admission, a rash was discovered on her left lumbar region with vesicles on top of an erythematous base. Varicella PCR was conducted on the patient's cerebrospinal fluid which was positive. Upon further history, patient was found to have previous varicella infection as a child, but no prior episodes of dermatomal zoster. Therefore, this patient was found to have aseptic meningitis and cutaneous manifestation of disseminated varicella-zoster despite immunocompetence. Antibacterial treatment was discontinued and she was continued on acyclovir for 7 days with transition to valacyclovir for 2 additional weeks with good treatment response and symptom resolution.

Incidence and Prevention of Herpes Zoster Reactivation in Patients with Autoimmune Diseases.

PubMed

Chakravarty, Eliza F

2017-02-01

Herpes zoster is the reactivation of latent varicella zoster virus usually occurring decades after initial exposure, and manifesting as a painful vesicular rash occurring along one or more dermatomes. Zoster incidence increases with age as cell mediated immunity against latent virus wanes. Epidemiological evidence suggests that individuals with underlying rheumatic diseases are at increased risk for zoster. It remains unclear whether this is due to immunosuppressive medications or from immune dysregulation of the underlying disease. A vaccine against zoster is available for individuals 50 years and older. Theoretical risks remain about using this live-attenuated virus vaccine in immunosuppressed individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

A Unique Case of Acute Cerebral Venous Sinus Thrombosis Secondary to Primary Varicella Zoster Virus Infection.

PubMed

Imam, Syed F; Lodhi, Omair Ul Haq; Fatima, Zainab; Nasim, Saneeya; Malik, Waseem T; Saleem, Muhammad Sabih

2017-09-16

Primary varicella zoster virus (VZV) infection, predominantly in the pediatric population, presents with pyrexia and a classic pruritic vesicular rash. In adults, although less common, it is more severe and linked to more complications. Neurological complications, which account for less than 1% of all VZV complications, include meningitis, encephalitis, arterial vasculopathy, and venous thrombosis. We present a case of a 39-year-old male who developed extensive cerebral venous sinus thrombosis following primary VZV infection. Venous thrombosis in VZV has been suggested to be caused by autoantibodies against protein S, pre-existing hypercoagulability, or endothelial damage. The patient was acutely managed using intravenous acyclovir and heparin. Long-term anticoagulation therapy with warfarin was continued after discharge. We concluded that clinicians should be aware of the rare complications of this common pathology so that a timely diagnosis can be made, followed by prompt management. Further studies need to be done to better understand acute cerebral venous sinus thrombosis secondary to VZV.

Chronic verrucous varicella-zoster virus infection in patients with the acquired immunodeficiency syndrome (AIDS). Histologic and molecular biologic findings.

PubMed

LeBoit, P E; Límová, M; Yen, T S; Palefsky, J M; White, C R; Berger, T G

1992-02-01

Verrucous skin lesions have been attributed to various herpes viruses in immunosuppressed patients, including those with human immunodeficiency virus infection (HIV). We examined such lesions from six HIV-infected patients to determine the range of microscopic findings present and to establish which herpesviruses were present. Verrucous epidermal hyperplasia, pseudocarcinomatous hyperplasia, and massive hyperkeratosis correlate with the warty clinical appearance of the lesions. Herpetic cytopathic changes, including multinucleated epidermal giant cells, steel-gray nuclei, necrotic acantholytic keratinocytes, and Cowdry type A nuclear inclusions were seen most prominently in the dells between papillations and in adnexal epithelium. In two cases, increased numbers of spindled cells were seen in the dermis. Immunoperoxidase staining with anti-type IV collagen antibodies demonstrated that these findings were not those of Kaposi's sarcoma, but represent a fibrotic reaction to the infection. Viral cultures of four of the cases demonstrated the presence of varicella-zoster virus, whose presence was detected by the polymerase chain reaction in paraffin-embedded lesional tissue from all six cases. Polymerase chain reaction did not show the presence of cytomegalovirus, herpes simplex, Epstein-Barr, or human papillomavirus. We conclude that these unusual verrucous lesions are a chronic manifestation of herpes zoster infection and that the reported presence of other agents in such lesions is probably coincidental.

Herpes zoster vaccine in Korea.

PubMed

Choi, Won Suk

2013-07-01

Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because of severe pain and complications, and cause considerable social and economic burden of disease. In 2012, herpes zoster vaccine was released in Korea. The efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over 60 and 69.8-72.4% among adults between 50 and 59. It is also known that preventive efficacy is maintained for at least 5 years. Although there can be local reactions such as redness, pain and swelling at the site of injection and systemic reaction such as headache and eruption after herpes zoster vaccination, most of the adverse reactions are minor and disappear within days by themselves. As it is a live vaccine, persons with severe immune-suppression and pregnant women should not be vaccinated with the vaccine. Currently, Korean Society of Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes zoster vaccine by subcutaneous route. In this article, clinical aspects and burden of disease of herpes zoster, efficacy and effects of herpes zoster vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious Diseases are discussed.

Herpes zoster vaccine in Korea

PubMed Central

2013-01-01

Herpes zoster and post-herpetic neuralgia deteriorate the quality of life because of severe pain and complications, and cause considerable social and economic burden of disease. In 2012, herpes zoster vaccine was released in Korea. The efficacy of herpes zoster vaccine is known to be 51.3-66.5% among the aged over 60 and 69.8-72.4% among adults between 50 and 59. It is also known that preventive efficacy is maintained for at least 5 years. Although there can be local reactions such as redness, pain and swelling at the site of injection and systemic reaction such as headache and eruption after herpes zoster vaccination, most of the adverse reactions are minor and disappear within days by themselves. As it is a live vaccine, persons with severe immune-suppression and pregnant women should not be vaccinated with the vaccine. Currently, Korean Society of Infectious Diseases recommended for the aged over 60 to be vaccinated with herpes zoster vaccine by subcutaneous route. In this article, clinical aspects and burden of disease of herpes zoster, efficacy and effects of herpes zoster vaccine, and herpes zoster vaccine recommendation by Korean Society of Infectious Diseases are discussed. PMID:23858399

Urinary retention, erectile dysfunction and meningitis due to sacral herpes zoster: a case report and review of the literature.

PubMed

Erol, B; Avci, A; Eken, C; Ozgok, Y

2009-01-01

Zona zoster infection is often associated with painful erythematous vesicular eruptions of the skin or mucous membranes. Varicella zoster virus which stays latent in the sensorial root ganglia causes zona zoster infection. The most recognized feature of zona zoster is the dermatomal distribution of vesicular rashes. In the present case report, we state an unusual presentation of sacral zona zoster with urinary retention, erectile dysfunction and meningitis. Copyright 2009 S. Karger AG, Basel.

A clinico-epidemiological study of herpes zoster.

PubMed

Aggarwal, S K; Radhakrishnan, S

2016-04-01

Herpes zoster is a common viral infection of skin caused by reactivation of varicella zoster virus infection from the spinal ganglia. The clinico-epidemiological patterns of this disease in an Indian setting required to be studied. A cross sectional study was conducted on all consecutive cases of herpes zoster reporting to the Dermatology Outpatient Department at a Tertiary Care Hospital in Bangalore during a period of one year from 01 Jun 2013 to 31 May 2014. Detailed history, examination, HIV screening and Tzanck smear were carried out in all cases. 84 cases of herpes zoster were seen with a mean age of 30 years. Majority (39%) of cases were seen in the 21-30 year age group. Thoracic segments were involved in 65.4%, cervical in 11.9%, cranial in 11.5%, lumbar in 8.3% and sacral segments in 3.5%. 63% of cases had zoster associated pain. One case had motor involvement.3.57% of the patients were HIV positive. This study shows a lower age incidence of herpes zoster HIV positivity and zoster associated pain as compared to other studies. The pattern of segmental involvement in herpes zoster seen in this study was similar to other studies.

Does monastic life predispose to the risk of Saint Anthony's fire (herpes zoster)?

PubMed

Gaillat, Jacques; Gajdos, Vincent; Launay, Odile; Malvy, Denis; Demoures, Bruno; Lewden, Lucie; Pinchinat, Sybil; Derrough, Tarik; Sana, Claudine; Caulin, Evelyne; Soubeyrand, Benoît

2011-09-01

The consequences of the epidemiology of varicella for zoster epidemiology are still debated. We therefore compared the frequency of herpes zoster in an adult population with virtually no varicella zoster virus (VZV) exposure with that in the general population (GP). We performed a national, multicenter, observational, exposed versus nonexposed, comparative study. The nonexposed population consisted of members of contemplative monastic orders (CMO) of the Roman Catholic Church living in 40 isolated monasteries in France. The exposed population consisted of a sample of the GP representative of the French population in terms of age group, sex, socio-occupational categories, and regions. The primary analysis population comprised 920 members of CMO (41.5% nuns; mean age, 64.2 years) and 1533 members of the GP (51.9% women; mean age, 64.6 years). The reported frequency of zoster was 16.2% among CMO and 15.1% in the GP (P = .27, adjusted for sex and age). The reported mean age of onset of zoster was 54.8 and 48.6 years, respectively (P = .06). This study failed to demonstrate an increased risk or earlier onset of zoster in members of CMO not exposed to VZV, compared with that in the GP. Although adults highly exposed to VZV could have a reduced risk of zoster, compared with the GP, our results suggest that the opposite is not true: adults not exposed to VZV are not at increased risk of zoster when compared with the GP, challenging the relevance of the assumptions and forecasts of current epidemiological models.

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association.

PubMed

Procop, Gary W; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D; Blandford, Alexander; Wilson, Deborah A; Hoffman, Gary S

2017-01-01

It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls.

Skin infections in pregnancy.

PubMed

Müllegger, Robert R; Häring, Nina S; Glatz, Martin

2016-01-01

A wide array of infectious diseases can occur in pregnancy. Their acquisition, clinical presentation, and course during gestation may be altered due to an impairment of the maternal cellular immunity. Some infectious diseases can lead to serious consequences for the mother or the offspring, including congenital malformations. This review describes in detail the clinical presentation, course, management, and associated maternal and fetal risks of selected viral (varicella-zoster virus infections, condylomata acuminata), fungal (candida vulvovaginitis), bacterial (Lyme borreliosis), and parasitic (scabies) infections. The treatment options are critically reviewed. First-line therapies include acyclovir and varicella-zoster virus immunoglobulin for varicella-zoster virus infections, surgical modalities for genital warts, topical clotrimazole and oral fluconazole for Candida vulvovaginitis, amoxicillin and cefuroxime for Lyme borreliosis, and permethrin for scabies. A synopsis of maternal and fetal risks of other important infections is also included. Copyright © 2016 Elsevier Inc. All rights reserved.

Evaluation of efficacy and effectiveness of live attenuated zoster vaccine.

PubMed

Gabutti, G; Valente, N; Sulcaj, N; Stefanati, A

2014-12-01

Herpes zoster (HZ) is a viral disease characterized by a dermatologic and neurologic involvement caused by the reactivation of the latent varicella zoster virus (VZV) acquired during primary infection (varicella). HZ incidence increases with age and is related to waning specific cell-mediated immunity (CMI). The most frequent complication of HZ is post-herpetic neuralgia (PHN) characterized by chronic pain lasting at least 30 days, with impact on patients' quality of life. Available treatments are quite unsatisfactory in reducing pain and length of the disease. The evaluation of the epidemiology, the debilitating complications (PHN), the suboptimal available treatments and the costs related to the diagnosis and clinical/therapeutic management of HZ patients have been the rationale for the search of an adequate preventive measure against this disease. The target of this intervention is to reduce the frequency and severity of HZ and related complications by stimulating CMI. Prevention has recently become possible with the live attenuated vaccine Oka/Merck, with an antigen content at least 10-fold higher than the antigen content of pediatric varicella vaccines. Clinical studies show a good level of efficacy and effectiveness, particularly against the burden of illness and PHN in all age classes. Accordingly to the summary of the characteristics of the product the zoster vaccine is indicated for the prevention of HZ and PHN in individuals 50 years of age or older and is effective and safe in subjects with a positive history of HZ.

Performance characteristics of a quantitative, standardised varicella zoster IgG time resolved fluorescence immunoassay (VZV TRFIA) for measuring antibody following natural infection.

PubMed

Chris Maple, P A; Gray, Jim; Brown, Kevin; Brown, David

2009-04-01

Infection by Varicella Zoster virus (VZV) during pregnancy has been associated with adverse foetal development and more severe disease in the mother. Accurate determination of VZV immunity in pregnant women exposed to VZV, with no history of chickenpox, guides therapeutic interventions. The accepted gold standard assay for the determination of immunity/protection against Varicella Zoster virus was for many years the fluorescent antibody to membrane antigen (FAMA) assay which is labour intensive and subjective. A validated alternative is the Merck glycoprotein EIA (Merck Sharp & Dohme Research Laboratories, West Point, PA, USA) which reports VZV IgG levels in enzyme units per ml (EU/ml) because an internal, non-international reference serum is used as calibrator. Comparison of different VZV IgG detection assays is hampered by a lack of an agreed cut-off in standardised units. A time resolved fluorescence immunoassay (TRFIA) for VZV IgG using British Standard VZV antibody has been developed and standardised. The limit of detection of VZV IgG by this assay was of the order 39-78mIU/ml. Following comparison with the Merck glycoprotein EIA and the application of the USA Advisory Committee on Immunization Practices recommended 5.0EU/ml cut-off the following standardised cut-offs in mIU/ml are proposed. A VZV TRFIA IgG cut-off of less than 100mIU/ml VZV IgG equates with susceptibility and an equivocal range of 100mIU/ml to less than 150mIU/ml is proposed. VZV IgG levels of 150mIU/ml, or greater, are indicative of natural infection at some time and the ability to mount a protective immune response is inferred.

Decrease in varicella incidence after implementation of the 2-dose recommendation for varicella vaccine in New Hampshire.

PubMed

Daly, Elizabeth R; Anderson, Ludmila; Dreisig, John; Dionne-Odom, Jodie

2013-09-01

Varicella is a common infectious disease, for which 2-dose vaccination was recommended in 2006. Varicella case and vaccination data in New Hampshire were analyzed to assess impact of this recommendation on disease incidence and clinical characteristics. Varicella incidence decreased after the 2-dose recommendation, with greatest reductions in ages 5-19 years. Continued vaccination efforts should further reduce disease.

Going Out on a Limb: Do Not Delay Diagnosis of Necrotizing Fasciitis in Varicella Infection.

PubMed

Sturgeon, Jonathan P; Segal, Laura; Verma, Anita

2015-07-01

Necrotizing fasciitis (NF) is a rare complication of varicella zoster (chicken pox) infection. Its diagnosis can be delayed or missed, which increases mortality and morbidity, because it initially presents similarly to cellulitis. We present the case of a 5-year-old boy who presented with a swollen leg, the difficulties in the diagnosis of NF, and a review of the literature. Necrotizing fasciitis complicating varicella zoster in children is associated with 3.4% mortality, although this rises to 13.6% in streptococcal toxic shock syndrome. Seventy-one percent of cases are confirmed as being caused by group A β-hemolytic Streptococcus. The association of NF with chicken pox is discussed along with the difficulties in diagnosis and treatment options. Necrotizing fasciitis is a surgical emergency and should be considered by all emergency department acute care practitioners in cases of varicella in which fever is enduring and swelling or pain is disproportionate. Because of the difficulty in diagnosis, senior opinion should be sought early.

Seroepidemiology of Varicella and value of self-reported history of Varicella infection in Iranian medical students.

PubMed

Allami, Abbas; Mohammadi, Navid; Najar, Azade

2014-04-01

We conducted this study to assess the seroprevalence of Varicella zoster virus (VZV) antibodies in a group of Iranian medical sciences students that were at risk of Varicella and the value of self-reported history as a predictor of immunity. 255 medical, nursing and obstetrics students who had not entered as a student or worked in a hospital from 3 different schools were enrolled in the study in 2012 (Qazvin province, Iran). Demographics and other information as well as the history of Varicella were obtained through a self-administered questionnaire. Blood samples were collected to determine the Varicella IgG levels via an enzyme-linked immunosorbent assay. A statistical analysis was performed by calculating prevalences and their 95% confidence intervals. Sensitivity, specificity, positive and negative predictive values, Cohen's kappa and positive and negative likelihood ratios of recalled history were determined. p < 0.05 was considered statistically significant. The mean age of participants was 21.3 ± 4.3 years. Seropositivity rate was 74.5%. The relationships between marital status, number of family members, and acquired VZV history with immunity against the virus were statistically significant. The overall rate of reported history was 57%. The positive and negative predictive values of self-reported history of Varicella were 91% and 47.3%, respectively. Immunization of students of Iranian medical sciences seems logical in the near future. Also, they should be tested for Varicella immunity regardless of the history of previous infection.

Mutations in RNA Polymerase III genes and defective DNA sensing in adults with varicella-zoster virus CNS infection.

PubMed

Carter-Timofte, Madalina E; Hansen, Anders F; Christiansen, Mette; Paludan, Søren R; Mogensen, Trine H

2018-05-01

Recently, deficiency in the cytosolic DNA sensor RNA Polymerase III was described in children with severe primary varicella-zoster virus (VZV) infection in the CNS and lungs. In the present study we examined adult patients with VZV CNS infection caused by viral reactivation. By whole exome sequencing we identified mutations in POL III genes in two of eight patients. These mutations were located in the coding regions of the subunits POLR3A and POLR3E. In functional assays, we found impaired expression of antiviral and inflammatory cytokines in response to the POL III agonist Poly(dA:dT) as well as increased viral replication in patient cells compared to controls. Altogether, this study provides significant extension on the current knowledge on susceptibility to VZV infection by demonstrating mutations in POL III genes associated with impaired immunological sensing of AT-rich DNA in adult patients with VZV CNS infection.

Penile herpes zoster: an unusual location for a common disease.

PubMed

Bjekic, Milan; Markovic, Milica; Sipetic, Sandra

2011-01-01

Herpes zoster is a common dermatological condition which affects up to 20% of the population, most frequently involving the thoracic and facial dermatomes with sacral lesions occurring rarely and only a few reported cases of penile shingles. We report two cases of unusual penile clinical presentations of varicella zoster virus infection in immunocompetent men. The patients presented with grouped clusters of vesicles and erythema on the left side of penile shaft and posterior aspect of the left thigh and buttock, involving s2-s4 dermatomes. The lesions resolved quickly upon administration of oral antiviral therapy. Penile herpes zoster should not be overlooked in patients with unilateral vesicular rash.

Rapid Detection of the Varicella Zoster Virus

NASA Technical Reports Server (NTRS)

Lewis, Michelle P.; Harding, Robert

2011-01-01

1.Technology Description-Researchers discovered that when the Varicella Zoster Virus (VZV) reactivates from latency in the body, the virus is consistently present in saliva before the appearance of skin lesions. A small saliva sample is mixed with a specialized reagent in a test kit. If the virus is present in the saliva sample, the mixture turns a red color. The sensitivity and specificity emanates from an antibody-antigen reaction. This technology is a rapid, non-invasive, point of-of-care testing kit for detecting the virus from a saliva sample. The device is easy to use and can be used in clinics and in remote locations to quickly detect VZV and begin treatment with antiviral drugs. 2.Market Opportunity- RST Bioscience will be the first and only company to market a rapid, same day test kit for the detection of VZV in saliva. The RST detection test kit will have several advantages over existing, competitive technology. The test kit is self contained and laboratory equipment is not required for analysis of the sample. Only a single saliva sample is required to be taken instead of blood or cerebral spinal fluid. The test kit is portable, sterile and disposable after use. RST detection test kits require no electrical power or expensive storage equipment and can be used in remote locations. 3.Market Analysis- According to the CDC, it is estimated that 1 million cases of shingles occur each year in the U.S. with more than half over the age of sixty. There is a high demand for rapid diagnostics by the public. The point-of-care testing (POCT) market is growing faster than other segments of in vitro diagnostics. According to a July 2007 InteLab Corporation industry report the overall market for POCT was forecast to increase from $10.3 billion in 2005 to $18.7 billion by 2011. The market value of this test kit has not been determined. 4.Competition- The VZV vaccine prevents 50% of cases and reduces neuralgia by 66%. The most popular test detects VZV-specific IgM antibody

Varicella zoster virus myelitis in two elderly patients: diagnostic value of nested polymerase chain reaction assay and antibody index for cerebrospinal fluid specimens.

PubMed

Takahashi, Teruyuki; Tamura, Masato; Miki, Kenji; Yamaguchi, Mai; Kanno, Akira; Nunomura, Satoshi; Ra, Chisei; Tamiya, Takashi; Kamei, Satoshi; Takasu, Toshiaki

2013-01-01

Myelitis is one of the rarest neurological complications of the varicella zoster virus (VZV) infection. Focal muscle weakness with or without sensory disturbance occurs in approximately 5% of the cases after acute VZV infection, with complete recovery in 50-70%. This report describes two rare cases of elderly patients with VZV myelitis secondary to dermatomal zoster rash. Patient 1 was a 79-year-old woman who developed paraplegia, numbness and decreased sensation in the left arm and below thoracic (Th)-10 after sacral zoster. Spinal cord MRI showed a high-signal-intensity lesion at the cervical spinal nerve 2 on a T2-weighted image. Patient 2 was a 73-year-old man who developed right flaccid leg weakness and urinary retention after right dorsal Th 5-8 zoster. Spinal cord MRI showed a high-signal-intensity lesion at Th 3-4 on a T2-weighted image. In both cases, although the conventional single polymerase chain reaction (PCR) assays all showed negative results, the original nested PCR assay detected VZV DNA in the cerebrospinal fluid (CSF) specimen collected on admission. In addition, the anti-VZV IgG antibody by enzyme immunoassay and antibody index were elevated in the CSF specimens during the clinical courses of both patients. On the basis of these findings, both patients were diagnosed with VZV myelitis and were treated with high-dose acyclovir and corticosteroid. This combined treatment was appropriate and effective for the improvement of their functional outcomes. The detection of VZV DNA in CSF by nested PCR assay and the evaluation of the antibody index to VZV had significant diagnostic value.

Sequential retinal necrosis secondary to varicella zoster in unrecognised long-standing HIV infection: patient safety report.

PubMed

Ning, Brigid Ky; Kelly, Simon P; Chu, Celia; Morgan, Emile

2018-03-21

A retired woman with left ophthalmic shingles of over 2 years' duration attended with bilateral vision loss and systemic upset. Acute retinal necrosis with detachment was detected on right fundus examination. Cataract in left eye precluded funduscopy. Ocular ultrasonography revealed fibrotic retinal detachment in the left eye. MRI brain and orbits also showed signals of retinal detachment. No abnormal MRI signal within the optic nerve or brain was found. Varicella zoster virus was detected in ocular aqueous and blood samples. High-dose intravenous acyclovir was administered. HIV test was positive with a very low CD4 count. Antiretroviral medications were prescribed. There was no recovery of vision. She was certified as blind, and social services were involved in seeking to provide alterations to her home in view of her severe disability. This case highlights the importance of suspecting HIV in patients with severe or chronic ophthalmic shingles. Images and implications for clinical practice are presented. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cost-effectiveness of varicella vaccine against herpes zoster and post-herpetic neuralgia for elderly in Japan.

PubMed

Hoshi, Shu-Ling; Kondo, Masahide; Okubo, Ichiro

2017-05-31

The extended use of varicella vaccine in adults aged 50 and older against herpes zoster (HZ) was recently approved in Japan, which has raised the need to evaluate its value for money. We conducted a cost-effectiveness analysis with Markov modelling to evaluate the efficiency of varicella vaccine immunisation programme for the elderly in Japan. Four strategies with different ages to receive a shot of vaccine were set, namely: (1) 65-84, (2) 70-84, (3) 75-84 and (4) 80-84years old (y.o.). Incremental cost-effectiveness ratios (ICERs) compared with no programme from societal perspective were calculated. The health statuses following the target cohort are as follows: without any HZ-related disease, acute HZ followed by recovery, post-herpetic neuralgia (PHN) followed by recovery, post HZ/PHN, and general death. The transition probabilities, utility weights to estimate quality-adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Costs of per course of vaccination were assumed at ¥10,000 (US$91). The model with one-year cycle runs until the surviving individual reached 100 y.o. ICERs ranged from ¥2,812,000/US$25,680 to ¥3,644,000/US$33,279 per QALY gained, with 65-84 y.o. strategy having the lowest ICER and 80-84 y.o. strategy the highest. None of the alternatives was strongly dominated by the other, while 80-84 y.o. and 70-84 y.o. strategy were extendedly dominated by 65-84 y.o. Probabilistic sensitivity analyses showed that the probabilities that ICER is under ¥5,000,000/US$45,662 per QALY gained was at 100% for 65-84 y.o., 70-84 y.o., 75-84 y.o. strategy, respectively, and at 98.4% for 80-84 y.o. We found that vaccinating individuals aged 65-84, 70-84, 75-84, and 80-84 with varicella vaccine to prevent HZ-associated disease in Japan can be cost-effective from societal perspective, with 65-84 y.o. strategy as the optimal alternative. Results are supported by one-way sensitivity analyses and probabilistic sensitivity

Varicella Zoster Virus and Large Vessel Vasculitis, the Absence of an Association

PubMed Central

Procop, Gary W.; Eng, Charis; Clifford, Alison; Villa-Forte, Alexandra; Calabrese, Leonard H.; Roselli, Eric; Svensson, Lars; Johnston, Douglas; Pettersson, Gosta; Soltesz, Edward; Lystad, Lisa; Perry, Julian D.; Blandford, Alexander; Wilson, Deborah A.; Hoffman, Gary S.

2017-01-01

Objective It is controversial whether microorganisms play a role in the pathogenesis of large and medium vessel vasculitides (eg, giant cell arteritis [GCA], Takayasu arteritis [TAK] and focal idiopathic aortitis [FIA]). Recent studies have reported the presence of Varicella Zoster Virus (VZV) within formalin-fixed, paraffin-embedded temporal arteries and aortas of about three-quarters or more of patients with these conditions, and in a minority of controls. In a prospective study, we sought to confirm these findings using DNA extracted from vessels that were harvested under surgically aseptic conditions and snap frozen. Methods and Results DNA samples extracted from 11 surgically sterile temporal arteries and 31 surgically sterile thoracic aortas were used in an attempt to identify the vessel-associated VZV genome. Two different validated PCR methods were used. Thirty-one thoracic aorta aneurysm specimens included biopsies from 8 patients with GCA, 2 from patients with TAK, 6 from patients with FIA, and 15 from patients without vasculitis, who had non-inflammatory aneurysms. Eleven temporal artery biopsies were collected from 5 patients with GCA and 6 controls. The presence of VZV was not identified in either the specimens from patients with large vessel vasculitis or from the controls. Conclusions Using surgically sterile snap-frozen specimens, we were unable to confirm recent reports of the presence of VZV in either aortas or temporal arteries from patients with large vessel vasculitis or controls. PMID:28758156

Varicella-zoster virus infections in patients treated with fingolimod: risk assessment and consensus recommendations for management.

PubMed

Arvin, Ann M; Wolinsky, Jerry S; Kappos, Ludwig; Morris, Michele I; Reder, Anthony T; Tornatore, Carlo; Gershon, Anne; Gershon, Michael; Levin, Myron J; Bezuidenhoudt, Mauritz; Putzki, Norman

2015-01-01

Varicella-zoster virus (VZV) infections increasingly are reported in patients with multiple sclerosis (MS) and constitute an area of significant concern, especially with the advent of more disease-modifying treatments in MS that affect T-cell-mediated immunity. To assess the incidence, risk factors, and clinical characteristics of VZV infections in fingolimod-treated patients and provide recommendations for prevention and management. Rates of VZV infections in fingolimod clinical trials are based on pooled data from the completed controlled phases 2 and 3 studies (3916 participants) and ongoing uncontrolled extension phases (3553 participants). Male and female patients aged 18 through 55 years (18-60 years for the phase 2 studies) and diagnosed as having relapsing-remitting MS were eligible to participate in these studies. In the postmarketing setting, reporting rates since 2010 were evaluated. In clinical trials, patients received fingolimod at a dosage of 0.5 or 1.25 mg/d, interferon beta-1a, or placebo. In the postmarketing setting, all patients received fingolimod, 0.5 mg/d (total exposure of 54,000 patient-years at the time of analysis). Calculation of the incidence rate of VZV infection per 1000 patient-years was based on the reporting of adverse events in the trials and the postmarketing setting. Overall, in clinical trials, VZV rates of infection were low but higher with fingolimod compared with placebo (11 vs 6 per 1000 patient-years). A similar rate was confirmed in the ongoing extension studies. Rates reported in the postmarketing settings were comparable (7 per 1000 patient-years) and remained stable over time. Disproportionality in reporting herpes zoster infection was higher for patients receiving fingolimod compared with those receiving other disease-modifying treatments (empirical Bayes geometric mean, 2.57 [90% CI, 2.26-2.91]); the proportion of serious herpes zoster infections was not higher than the proportion for other treatments (empirical

[Seroprevalence of varicella-zoster virus in children with cancer in six hospitals in Santiago, Chile].

PubMed

Izquierdo, Giannina; Zubieta, Marcela; Martínez G, María J; Alvarez, Ana M; Aviles, Carmen L; Becker, Ana; Peña, Mónica; Salgado, Carmen; Silva, Pamela; Topelberg, Santiago; Tordecilla, Juan; Varas, Mónica; Villarroel, Milena; Viviani, Tamara; Santolaya, María E

2012-12-01

Infections with varicella-zoster virus (VVZ) in immunocompromised children imply a high mortality. There is no data about VVZ seroprevalence in children with cancer in our country. To determine the prevalence of VVZ antibodies in children with cancer who have undergone chemotherapy or have undergone a hematopoietic stem cell transplant. collaborative, multicenter study. Serum samples were collected from 281 children with cancer and episodes of febrile neutropenia from 6 hospitals belonging to the public health network in the Metropolitan Region between June 2004 and August 2006. These samples were stored at -70 ° C, and 200 of them were randomly chosen and analyzed to determine VVZ IgG (ELISA). 179 samples from 179 children, 65% male. Ninety eighth/179 (55%) were positive, 72/179 (40%) negative and 9/179 (5%) indeterminate. Stratified by age, seropositive percentage was: 1 to 4 years 32%, 5-9 years 42%, 10-14 years 78%, over 15 years 88%. Forty percent of children treated for cancer are seronegative to VVZ infection, a frequency that decreases with age. These results support the adoption of preventive measures to avoid infection in this population of children at risk of developing a serious and possibly fatal illness.

Challenges with controlling varicella in prison settings: experience of California, 2010 to 2011.

PubMed

Leung, Jessica; Lopez, Adriana S; Tootell, Elena; Baumrind, Nikki; Mohle-Boetani, Janet; Leistikow, Bruce; Harriman, Kathleen H; Preas, Christopher P; Cosentino, Giorgio; Bialek, Stephanie R; Marin, Mona

2014-10-01

This article describes the epidemiology of varicella in one state prison in California during 2010 and 2011, control measures implemented, and associated costs. Eleven varicella cases were reported, of which nine were associated with two outbreaks. One outbreak consisted of three cases and the second consisted of six cases with two generations of spread. Among exposed inmates serologically tested, 98% (643/656) were varicella-zoster virus seropositive. The outbreaks resulted in > 1,000 inmates exposed, 444 staff exposures, and > $160,000 in costs. The authors documented the challenges and costs associated with controlling and managing varicella in a prison setting. A screening policy for evidence of varicella immunity for incoming inmates and staff and vaccination of susceptible persons has the potential to mitigate the impact of future outbreaks and reduce resources necessary to manage cases and outbreaks. © The Author(s) 2014.

Epidemiology, treatment and prevention of herpes zoster: A comprehensive review.

PubMed

Koshy, Elsam; Mengting, Lu; Kumar, Hanasha; Jianbo, Wu

2018-01-01

Herpes zoster is a major health burden that can affect individuals of any age. It is seen more commonly among individuals aged ≥50 years, those with immunocompromised status, and those on immunosuppressant drugs. It is caused by a reactivation of varicella zoster virus infection. Cell-mediated immunity plays a role in this reactivation. Fever, pain, and itch are common symptoms before the onset of rash. Post-herpetic neuralgia is the most common complication associated with herpes zoster. Risk factors and complications associated with herpes zoster depend on the age, immune status, and the time of initializing treatment. Routine vaccination for individuals over 60 years has shown considerable effect in terms of reducing the incidence of herpes zoster and post-herpetic neuralgia. Treatment with antiviral drugs and analgesics within 72 hours of rash onset has been shown to reduce severity and complications associated with herpes zoster and post-herpetic neuralgia. This study mainly focuses on herpes zoster using articles and reviews from PubMed, Embase, Cochrane library, and a manual search from Google Scholar. We cover the incidence of herpes zoster, gender distribution, seasonal and regional distribution of herpes zoster, incidence of herpes zoster among immunocompromised individuals, incidence of post-herpetic neuralgia following a zoster infection, complications, management, and prevention of herpes zoster and post-herpetic neuralgia.

Entrapment of viral capsids in nuclear PML cages is an intrinsic antiviral host defense against varicella-zoster virus.

PubMed

Reichelt, Mike; Wang, Li; Sommer, Marvin; Perrino, John; Nour, Adel M; Sen, Nandini; Baiker, Armin; Zerboni, Leigh; Arvin, Ann M

2011-02-03

The herpesviruses, like most other DNA viruses, replicate in the host cell nucleus. Subnuclear domains known as promyelocytic leukemia protein nuclear bodies (PML-NBs), or ND10 bodies, have been implicated in restricting early herpesviral gene expression. These viruses have evolved countermeasures to disperse PML-NBs, as shown in cells infected in vitro, but information about the fate of PML-NBs and their functions in herpesvirus infected cells in vivo is limited. Varicella-zoster virus (VZV) is an alphaherpesvirus with tropism for skin, lymphocytes and sensory ganglia, where it establishes latency. Here, we identify large PML-NBs that sequester newly assembled nucleocapsids (NC) in neurons and satellite cells of human dorsal root ganglia (DRG) and skin cells infected with VZV in vivo. Quantitative immuno-electron microscopy revealed that these distinctive nuclear bodies consisted of PML fibers forming spherical cages that enclosed mature and immature VZV NCs. Of six PML isoforms, only PML IV promoted the sequestration of NCs. PML IV significantly inhibited viral infection and interacted with the ORF23 capsid surface protein, which was identified as a target for PML-mediated NC sequestration. The unique PML IV C-terminal domain was required for both capsid entrapment and antiviral activity. Similar large PML-NBs, termed clastosomes, sequester aberrant polyglutamine (polyQ) proteins, such as Huntingtin (Htt), in several neurodegenerative disorders. We found that PML IV cages co-sequester HttQ72 and ORF23 protein in VZV infected cells. Our data show that PML cages contribute to the intrinsic antiviral defense by sensing and entrapping VZV nucleocapsids, thereby preventing their nuclear egress and inhibiting formation of infectious virus particles. The efficient sequestration of virion capsids in PML cages appears to be the outcome of a basic cytoprotective function of this distinctive category of PML-NBs in sensing and safely containing nuclear aggregates of aberrant

Do HIV-positive adult immigrants need to be screened for measles-mumps-rubella and varicella zoster virus immunization?

PubMed

Llenas-García, Jara; Rubio, Rafael; Hernando, Asunción; Arrazola, Pilar; Pulido, Federico

2013-08-01

A systematic screening for measles, mumps, rubella (MMR) and varicella zoster virus (VZV) in HIV-positive adult immigrants in Spain was evaluated, and factors associated with MMR and VZV vaccines' indication were studied. Every HIV-positive immigrant was tested for VZV and MMR-IgG. MMR vaccine was indicated to patients with lymphocytes CD4+ >200 cells/mm³ and a negative measles-IgG, a negative mumps-IgG and/or a negative rubella-IgG. VZV vaccine was indicated to every VZV-IgG negative patient with CD4+ >400 cells/mm³. In total, 289 patients were screened; seroprevalence was 95.2%, 92.2%, 70.3% and 89.3% for VZV, measles, mumps and rubella IgG, respectively. Having a negative VZV-IgG was statistically associated with coming from sub-Saharan Africa (prevalence ratio [PR]: 6.52; 95% CI: 1.71-24.84; p=0.006), while having secondary education was a protective factor (PR: 0.25; 95% CI: 0.07-0.97; p=0.045). Fourteen patients (4.8%) had indication of VZV vaccine; vaccination was feasible in 21.4% of them at first visit. Eighty-one patients (29.7%) had indication of MMR vaccine, most of them due to mumps-IgG negative (53.1%) or rubella-IgG negative (24.7%). Age < 30 years at first visit was the only factor statistically associated with MMR vaccine indication (PR: 1.47; 95% CI: 1.02-2.11; p=0.04). According to CD4+ cell counts, vaccination was feasible in 71.6% of patients at first visit. In conclusion, more than a third of HIV-infected immigrant patients are susceptible to at least one easily preventable infectious disease. Especial attention should be given to immigrant women of childbearing age.

T-Cell Tropism of Simian Varicella Virus during Primary Infection

PubMed Central

Ouwendijk, Werner J. D.; Mahalingam, Ravi; de Swart, Rik L.; Haagmans, Bart L.; van Amerongen, Geert; Getu, Sarah; Gilden, Don; Osterhaus, Albert D. M. E.; Verjans, Georges M. G. M.

2013-01-01

Varicella-zoster virus (VZV) causes varicella, establishes a life-long latent infection of ganglia and reactivates to cause herpes zoster. The cell types that transport VZV from the respiratory tract to skin and ganglia during primary infection are unknown. Clinical, pathological, virological and immunological features of simian varicella virus (SVV) infection of non-human primates parallel those of primary VZV infection in humans. To identify the host cell types involved in virus dissemination and pathology, we infected African green monkeys intratracheally with recombinant SVV expressing enhanced green fluorescent protein (SVV-EGFP) and with wild-type SVV (SVV-wt) as a control. The SVV-infected cell types and virus kinetics were determined by flow cytometry and immunohistochemistry, and virus culture and SVV-specific real-time PCR, respectively. All monkeys developed fever and skin rash. Except for pneumonitis, pathology produced by SVV-EGFP was less compared to SVV-wt. In lungs, SVV infected alveolar myeloid cells and T-cells. During viremia the virus preferentially infected memory T-cells, initially central memory T-cells and subsequently effector memory T-cells. In early non-vesicular stages of varicella, SVV was seen mainly in perivascular skin infiltrates composed of macrophages, dendritic cells, dendrocytes and memory T-cells, implicating hematogenous spread. In ganglia, SVV was found primarily in neurons and occasionally in memory T-cells adjacent to neurons. In conclusion, the data suggest the role of memory T-cells in disseminating SVV to its target organs during primary infection of its natural and immunocompetent host. PMID:23675304

Varicella epidemiology in Latin America and the Caribbean.

PubMed

Ávila-Agüero, Maria L; Beltrán, Sandra; Castillo, José Brea Del; Castillo Díaz, María Esther; Chaparro, Luis Eduardo; Deseda, Carmen; Debbag, Roberto; Espinal, Carlos; Falleiros-Arlant, Luiza Helena; González Mata, Antonio José; Macías Parra, Mercedes; Marques-Rosa, Fabiano; Catalina Pírez, María; Vázquez-Rivera, Mirella

2018-02-01

The Latin American Society of Pediatric Infectious Diseases (SLIPE), with the support of the Americas Health Foundation (AHF), has developed a position paper on varicella prevention in Latin America and Caribbean countries (LAC). This article summarizes the most relevant aspects of varicella in LAC, and emphasizes the need to include the varicella vaccine in the national immunization programs in the Region and evaluate its impact disease burden. Areas covered: A systematic review was conducted of the medical evidence published and presented at various regional medical conferences on the disease burden in LAC, the advances made by prevention programs, the available vaccines in the Region, and their immunogenicity, efficacy, effectiveness, and safety. The different national varicella-prevention vaccination programs were reviewed, as was available information regarding the impact of these programs on the epidemiology of varicella in those countries implementing a varicella vaccine strategy. Following that initial publication, an update was conducted, including data from additional countries in the Region. Expert commentary: Varicella is a vaccine-preventable infectious disease, considered a 'benign disease' because of lower complication rates when compared with measles, pertussis. The incorporation of a two-dose varicella vaccine in national immunization schedules in all countries throughout LAC would be of great benefit to the health of the children.

Antibody persistence for 3 years following two doses of tetravalent measles-mumps-rubella-varicella vaccine in healthy children.

PubMed

Knuf, Markus; Zepp, Fred; Helm, Klaus; Maurer, Hartwig; Prieler, Albrecht; Kieninger-Baum, Dorothee; Douha, Martine; Willems, Paul

2012-03-01

Two doses of a varicella-containing vaccine in healthy children <12 years are suggested to induce better protection than a single dose. Persistence of immunity against measles, mumps, rubella, and varicella as well as varicella breakthrough cases were assessed 3 years after two-dose measles, mumps, rubella, and varicella (MMRV) vaccination or concomitant MMR (Priorix™) and varicella (Varilrix™) vaccination. Four hundred ninety-four healthy children, 12-18 months old at the time of the first dose, received either two doses of MMRV vaccine (GlaxoSmithKline Biologicals) 42-56 days apart (MMRV, N = 371) or one dose of MMR and varicella vaccines administered simultaneously at separate sites, followed by another MMR vaccination 42-56 days later (MMR + V, N = 123). Three hundred-four subjects participated in 3-year follow-up for persistence of immunity and occurrence of breakthrough varicella (MMRV, N = 225; MMR + V, N = 79). Antibodies were measured by ELISA (measles, mumps, rubella) and immunofluorescence (varicella). Contacts with individuals with varicella or zoster and cases of breakthrough varicella disease were recorded. Three years post-vaccination seropositivity rates in subjects seronegative before vaccination were: MMRV-measles, 98.5% (geometric mean titer [GMT] = 3,599.6); mumps, 97.4% (GMT = 1,754.5); rubella, 100% (GMT = 51.9); varicella, 99.4% (GMT = 225.5); MMR + V-measles, 97.0% (GMT = 1,818.8); mumps, 93.8% (GMT = 1,454.6); rubella, 100% (GMT = 53.8); and varicella, 96.8% (GMT = 105.8). Of the subjects, 15-20% reported contact with individuals with varicella/zoster each year. After 3 years, the cumulative varicella breakthrough disease rate was 0.7% (two cases) in the MMRV group and 5.4% (five cases) in the MMR + V group. Immunogenicity of the combined MMRV vaccine was sustained 3 years post-vaccination. (208136/041/NCT00406211).

Mitochondrial Haplogroups as a Risk Factor for Herpes Zoster.

PubMed

Levinson, Rebecca T; Hulgan, Todd; Kalams, Spyros A; Fessel, Joshua P; Samuels, David C

2016-10-01

Background.  Herpes zoster, or shingles, is a common, painful reactivation of latent varicella zoster virus infection. Understanding host factors that predispose to herpes zoster may permit development of more effective prevention strategies. Our objective was to examine mitochondrial haplogroups as a potential host factor related to herpes zoster incidence. Methods.  Study participants were drawn from BioVU, a deoxyribonucleic acid (DNA) biobank connected to deidentified electronic medical records (EMRs) from Vanderbilt University Medical Center. Our study used 9691 Caucasian individuals with herpes zoster status determined by International Classification of Diseases, Ninth Revision codes 053-053.9. Cases and controls were matched on sex and date of birth within 5 years. Mitochondrial haplogroups were defined from mitochondrial DNA variants genotyped on the Illumina 660W or Illumina Infinium Human-Exome Beadchip. Sex and date of birth were extracted from the EMR. Results.  European mitochondrial haplogroup H had a protective association with herpes zoster status (odds ratio [OR] = .82; 95% confidence interval [CI], .71-.94; P = .005), whereas haplogroup clade IWX was a risk factor for herpes zoster status (OR = 1.38; 95% CI, 1.07-1.77; P = .01). Conclusions.  Mitochondrial haplogroup influences herpes zoster risk. Knowledge of a patient's mitochondrial haplogroup could allow for a precision approach to the management of herpes zoster risk through vaccination strategies and management of other modifiable risk factors.

Providers' lack of knowledge about herpes zoster in HIV-infected patients is among barriers to herpes zoster vaccination.

PubMed

Aziz, M; Kessler, H; Huhn, G

2013-06-01

Identification of perceptions about herpes zoster (HZ) disease, vaccine effectiveness and safety, and vaccine recommendations may impact immunization practices of physicians for HIV-infected patients. A survey was used to quantify knowledge of HZ as well as determine physician immunization perceptions and practices. There were 272/1700 respondents (16%). Correct answers for the incidence of varicella zoster virus (VZV) infection in adults and incidence of HZ in HIV-infected patients were recorded by 14% and 10% of providers, respectively. Providers reported poor knowledge of the incidence of disease recurrence in HIV-infected patients (41% correct), potency of HZ vaccine (47.5% correct) and mechanism of protection against reactivation of VZV (66% correct). Most (88%) agreed that HZ was a serious disease, and 73% believed that the burden of disease made vaccination important. A majority (75%) did not vaccinate HIV patients with HZ vaccine regardless of antiretroviral therapy status. Barriers to administration included safety concerns, concern that vaccine would not prevent HZ, risk of HZ dissemination, reimbursement issues and lack of Infectious Diseases Society of America (IDSA) guidelines. Only 38% of providers agreed that CDC guidelines were clear and 50% believed that clinical trials were needed prior to use of HZ vaccine in HIV-infected patients. Education about HZ is needed among HIV providers. Providers perceived vaccination as important, but data on vaccine safety and clear guidance from the CDC on this issue are lacking.

Use of a bacterial expression vector to map the varicella-zoster virus major glycoprotein gene, gC.

PubMed Central

Ellis, R W; Keller, P M; Lowe, R S; Zivin, R A

1985-01-01

The genome of varicella-zoster virus (VZV) encodes at least three major glycoprotein genes. Among viral gene products, the gC gene products are the most abundant glycoproteins and induce a substantial humoral immune response (Keller et al., J. Virol. 52:293-297, 1984). We utilized two independent approaches to map the gC gene. Small fragments of randomly digested VZV DNA were inserted into a bacterial expression vector. Bacterial colonies transformed by this vector library were screened serologically for antigen expression with monoclonal antibodies to gC. Hybridization of the plasmid DNA from a gC antigen-positive clone revealed homology to the 3' end of the VZV Us segment. In addition, mRNA from VZV-infected cells was hybrid selected by a set of VZV DNA recombinant plasmids and translated in vitro, and polypeptide products were immunoprecipitated by convalescent zoster serum or by monoclonal antibodies to gC. This analysis revealed that the mRNA encoding a 70,000-dalton polypeptide precipitable by anti-gC antibodies mapped to the HindIII C fragment, which circumscribes the entire Us region. We conclude that the VZV gC glycoprotein gene maps to the 3' end of the Us region and is expressed as a 70,000-dalton primary translational product. These results are consistent with the recently reported DNA sequence of Us (A.J. Davison, EMBO J. 2:2203-2209, 1983). Furthermore, glycosylation appears not to be required for a predominant portion of the antigenicity of gC glycoproteins. We also report the tentative map assignments for eight other VZV primary translational products. Images PMID:2981365

Meta-Analysis of Infectious Agents and Depression

PubMed Central

Wang, Xiao; Zhang, Liang; Lei, Yang; Liu, Xia; Zhou, Xinyu; Liu, Yiyun; Wang, Mingju; Yang, Liu; Zhang, Lujun; Fan, Songhua; Xie, Peng

2014-01-01

Depression is a debilitating psychiatric disorder and a growing global public health issue. However, the relationships between microbial infections and depression remains uncertain. A computerized literature search of Medline, ISI Web of Knowledge, PsycINFO, and the Cochrane Library was conducted up to May 2013, and 6362 studies were initially identified for screening. Case-control studies detected biomarker of microorganism were included. Based on inclusion and exclusion criteria, 28 studies were finally included to compare the detection of 16 infectious agents in unipolar depressed patients and healthy controls with a positive incident being defined as a positive biochemical marker of microbial infection. A customized form was used for data extraction. Pooled analysis revealed that the majority of the 16 infectious agents were not significantly associated with depression. However, there were statistically significant associations between depression and infection with Borna disease virus, herpes simplex virus-1, varicella zoster virus, Epstein-Barr virus, and Chlamydophila trachomatis. PMID:24681753

Prevention strategies for herpes zoster and post-herpetic neuralgia

PubMed Central

Levin, Myron J.; Gershon, Anne A.; Dworkin, Robert H.; Brisson, Marc; Stanberry, Lawrence

2017-01-01

SUMMARY Impairment of varicella zoster virus (VZV)-specific cell-mediated immunity, including impairment due to immunosenescence, is associated with an increased risk of developing herpes zoster (HZ), whereas levels of anti-VZV antibodies do not correlate with HZ risk. This crucial role of VZV-specific cell-mediated immunity suggests that boosting these responses by vaccination will be an effective strategy for reducing the burden of HZ. Other strategies focus on preventing the major complication of HZ – post-herpetic neuralgia. These strategies include pre-emptive treatment with drugs such as tricyclic antidepressants, anticonvulsants and analgesics. PMID:20510262

A Case of Peri-Anal Varicella and Review of the Literature

ERIC Educational Resources Information Center

Barrett, Sabrina; Burgess, Scott

2011-01-01

Grouped vesicle on an erythematous base suggests a herpes virus infection and located within the anogenital region raises the possibility of sexual assault. The following case and review highlight the need to consider infection by varicella zoster virus in such cases and emphasises the importance of a prompt and accurate diagnosis.

Susceptibility to varicella-zoster infection in individuals 1 to 29 years of age in Mexico.

PubMed

Alvarez y Muñoz, M T; Torres, J; Damasio-Santana, L; Gómez, A; Fernández-Quintanilla, G; Tapia-Conyer, R; Muñoz, O

1999-01-01

The prevalence of varicella zoster virus (VZV) infection has been poorly studied in Latin America. The aim of this work was to study the seroprevalence of antibody to VZV infection in Mexico. Infection was determined in 3,737 individuals. Samples were collected during a national serologic survey performed during 1987-1988 and represented individuals 1- to 29-years-old from all socioeconomic levels and from rural and urban communities throughout the country. Antibodies anti-VZV were measured with a commercially available enzyme-linked immunosorbent assay (VARELISA Merck, Germany). In the population studied, 464 individuals (12.4%) were seronegative or susceptible to infection, whereas about 17.0% of individuals 1- to 19-years-old were susceptible to infection. Between the ages of 20 to 24 years, 8.4% were susceptible and between 25 to 29 years, 5.0% of persons were still susceptible to infection. Socioeconomic level, density of population, crowding, and gender were not found as risk factors for susceptibility to VZV infection in adolescents and young adults. Low educational level was found as a risk factor for susceptibility. High proportions of adolescents and young adults in Mexico are susceptible to VZV infection and should receive special attention when designing vaccination programs.

Contacts with children and young people and adult risk of suffering herpes zoster.

PubMed

Salleras, M; Domínguez, A; Soldevila, N; Prat, A; Garrido, P; Torner, N; Borrás, E; Salleras, L

2011-10-13

We carried out a matched case-control study to analyze the possible association between exposure to the children and the risk of suffering herpes-zoster in adulthood. Cases of herpes zoster in immunocompetent healthy patients aged ≥ 25 years seen in the dermatology department of the Sagrado Corazón Hospital in 2007-2008 were matched with four controls. Data were analyzed using conditional logistic regression. 153 cases and 604 matched controls were included. Contacts with children were significantly associated with a reduction in the risk of suffering herpes zoster in adulthood (adjusted OR 0.56 [0.37-0.85]). Herpes-zoster vaccination in immunocompetent people aged ≥ 50 years could counteract the possible negative effects of mass varicella vaccination in childhood on the epidemiology of herpes zoster in adults. Copyright © 2011 Elsevier Ltd. All rights reserved.

Safety, tolerability, and immunogenicity of zoster vaccine in subjects on chronic/maintenance corticosteroids.

PubMed

Russell, Amy F; Parrino, Janie; Fisher, Chester L; Spieler, Wolfgang; Stek, Jon E; Coll, Kathleen E; Su, Shu-Chih; Xu, Jin; Li, Xiaoming; Schlienger, Katia; Silber, Jeffrey L

2015-06-17

This randomized, placebo-controlled study assessed the safety, tolerability, and immunogenicity of live virus zoster vaccine (ZV) in individuals receiving chronic/maintenance systemic corticosteroid therapy (daily dose equivalent of 5-20mg prednisone) for ≥2 weeks prior to vaccination and ≥6 weeks postvaccination. Subjects were followed for adverse experiences (AEs), exposure to varicella or herpes zoster (HZ), or development of varicella/varicella-like or HZ/HZ-like rashes for 42 days postvaccination (primary safety follow-up period) and for serious AEs (SAEs) through Day 182 postvaccination (secondary follow-up period). Varicella-zoster virus (VZV) antibody titers by glycoprotein enzyme-linked immunosorbent assay (gpELISA) were measured at baseline and at Week 6 postvaccination. The proportions of subjects reporting systemic AEs and SAEs were similar in both groups. A higher percentage of subjects reported injection-site AEs in the ZV group (21.5%) than in the placebo group (12.1%). One SAE of ophthalmic HZ (onset Day 16 postvaccination) was reported in the ZV group and deemed vaccine-related by the study investigator; however, PCR testing confirmed the presence of wild-type (not vaccine strain) VZV. Geometric mean titer (GMT) at 6 weeks postvaccination was higher for ZV recipients than placebo recipients, with estimated geometric mean fold rises (GMFR) of 2.3 (CI: 2.0, 2.7) and 1.1 (CI: 1.0, 1.2) respectfully. In adults ≥60 years old on chronic/maintenance corticosteroids, ZV was generally well tolerated and immunogenic. The VZV-specific gpELISA antibody GMT at 6 weeks postvaccination and the GMFR from baseline to 6 weeks postvaccination were higher in the ZV group than in the placebo group. Copyright © 2015 Elsevier Ltd. All rights reserved.

Herpes Zoster Ophthalmicus.

PubMed

Johnson, Julie L; Amzat, Rianot; Martin, Nicolle

2015-09-01

Herpes zoster is a commonly encountered disorder. It is estimated that there are approximately 1 million new cases of herpes zoster in the United States annually, with an incidence of 3.2 per 1000 person-years. Patients with HIV have the greatest risk of developing herpes zoster ophthalmicus compared with the general population. Other risk factors include advancing age, use of immunosuppressive medications, and primary infection in infancy or in utero. Vaccination against the virus is a primary prevention modality. Primary treatments include antivirals, analgesics, and anticonvulsants. Management may require surgical intervention and comanagement with pain specialists, psychiatrists, and infectious disease specialists. Copyright © 2015 Elsevier Inc. All rights reserved.

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus: No association with subclinical viral reactivations or lupus disease activity.

PubMed

Rondaan, C; van Leer, C C; van Assen, S; Bootsma, H; de Leeuw, K; Arends, S; Bos, N A; Westra, J

2018-07-01

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia.

Novel polyvalent live vaccine against varicella-zoster and mumps virus infections.

PubMed

Matsuura, Masaaki; Somboonthum, Pranee; Murakami, Kouki; Ota, Megumi; Shoji, Masaki; Kawabata, Kenji; Mizuguchi, Hiroyuki; Gomi, Yasuyuki; Yamanishi, Koichi; Mori, Yasuko

2013-10-01

The varicella-zoster virus (VZV) Oka vaccine strain (vOka) is a highly immunogenic and safe live vaccine that has long been used worldwide. Because its genome is large, making it suitable for inserting foreign genes, vOka is considered a candidate vector for novel polyvalent vaccines. Previously, a recombinant vOka, rvOka-HN, that expresses mumps virus (MuV) hemagglutinin-neuraminidase (HN) was generated by the present team. rvOka-HN induces production of neutralizing antibodies against MuV in guinea pigs. MuV also expresses fusion (F) protein, which is important for inducing neutralizing antibodies, in its viral envelope. To induce a more robust immune response against MuV than that obtained with rvOka-HN, here an rvOka expressing both HN and F (rvOka-HN-F) was generated. However, co-expression of HN and F caused the infected cells to form syncytia, which reduced virus titers. To reduce the amount of cell fusion, an rvOka expressing HN and a mutant F, F(S195Y) were generated. Almost no syncytia formed among the rvOka-HN-F(S195Y)-infected cells and the growth of rvOka-HN-F(S195Y) was similar to that of the original vOka clone. Moreover, replacement of serine 195 with tyrosine had no effect on the immunogenicity of F in mice and guinea pigs. Although obvious augmentation of neutralizing antibody production was not observed after adding F protein to vOka-HN, the anti-F antibodies did have neutralizing activity. These data suggest that F protein contributes to induction of immune protection against MuV. Therefore this recombinant virus is a promising candidate vaccine for polyvalent protection against both VZV and MuV. © 2013 The Societies and Wiley Publishing Asia Pty Ltd.

[Antibody titers against measles, rubella, mumps and varicella-zoster viruses in medical students].

PubMed

Yoshida, Noriko; Tsumura, Naoki; Toyomasu, Koji; Sagawa, Kimitaka

2007-01-01

It is important to identify and immunize susceptible students who have clinical practice to prevent and control hospital infections. The antibody titers to measles, rubella, mumps and varicella viruses were measured in 1,139 students(417 men, 722 women, average age 21.3+/-2.7 yr old)including 510 medical students, 442 nursing students and 187 students of the School of Medical Technology in Kurume University. Antibodies against measles virus were detected by particle agglutination assay(PA), those against rubella virus by hemagglutination inhibition assay(HI), and those against mumps and varicella viruses by enzyme-linked immunosorbent assay(EIA). The serological susceptibilities to measles, rubella, mumps and varicella viruses were 112(9.8%), 112(9.8%), 163(14.3%)and 73(6.4%), respectively. The serological susceptibilities to measles, rubella and mumps viruses in male students were not different from those in female students. The susceptibility to varicella virus in female students was significantly higher than that in male students. After susceptible students were recommended to have vaccinations against each virus, the vaccination rate of the students without antibody was 99.1%. The history of infection and vaccination against the viruses were examined by self-recorded questionnaires in 406 students from all disciplines. The serological susceptibility of students with positive vaccination history was 11.1% for measles, 6.8% for rubella, 18.3% for mumps, and 4.9% for varicella. The serological susceptibility of students with a positive infection history was 5.7% for measles, 3.4% for rubella, 2.9% for mumps, and 4.9% for varicella. In the self-recorded questionnaire, the rate of unknown infection and vaccination histories were 57.5% and 71.6% for measles, 52.5% and 68.4% for rubella, 34.3% and 75.6% for mumps, and 27.1% and 80.5% for varicella, respectively. In conclusion, these data confirm that it is essential to assess immune status against measles, rubella

Close correlation of herpes zoster-induced voiding dysfunction with severity of zoster-related pain: A single faculty retrospective study.

PubMed

Fujii, Mizue; Takahashi, Ichiro; Honma, Masaru; Ishida-Yamamoto, Akemi

2015-11-01

Herpes zoster (HZ), a common vesiculo-erythematous skin disease associated with reactivation of varicella zoster virus in the cranial nerve, dorsal root, and autonomic ganglia, is accompanied by several related symptoms represented by postherpetic neuralgia. Among them, involvement of vesicorectal dysfunction is relatively rare. The vesicorectal symptom can usually be recovered in transient course, but is quite important in terms of impaired quality of life. Male individuals affected with HZ and skin lesions on sacral dermatome have been reported as independent risk factors of zoster-related voiding dysfunction. In this study, urinary symptoms were focused upon and six patients with zoster-related voiding dysfunction at a single faculty of dermatology in Japan from 2009 to 2014 were retrospectively analyzed. All patients showed HZ lesions on the sacral area and the urinary symptom recovered in approximately 2 months (14 days to 7 months). The term of treatment for zoster-associated urinary dysfunction was positively correlated with that for zoster-related pain without significance (r = 0.661, P = 0.153). Average treatment term for pain relief of sacral HZ accompanied by voiding dysfunction (91.3 ± 76.44 days) was significantly longer than that of sacral HZ without urinary symptom (18.9 ± 20.42 days) (P = 0.032). These results suggested that zoster-related voiding dysfunction would mainly be involved in sacral HZ and closely associated with severity of zoster-related pain. Dermatologists should be aware that severe zoster-related pain accompanied by sacral HZ, which is related to prolonged treatment of pain relief, can be a predictive factor of voiding dysfunction. © 2015 Japanese Dermatological Association.

Family history of zoster and risk of developing herpes zoster.

PubMed

Tseng, Hung Fu; Chi, Margaret; Hung, Peggy; Harpaz, Rafael; Schmid, D Scott; LaRussa, Philip; Sy, Lina S; Luo, Yi; Holmquist, Kimberly; Takhar, Harpreet; Jacobsen, Steven J

2018-01-01

Studies have investigated a possible association between family history of HZ and the occurrence of HZ. However, the results were inconclusive and susceptible to bias. We evaluated this association in an elderly population. The matched case-control study conducted at Kaiser Permanente Southern California in 2012-2015 included 656 incident HZ patients ≥60 whose skin lesion tested positive for varicella zoster virus by polymerase chain reaction. Half of the HZ patients were vaccinated with zoster vaccine as achieved by stratified sampling. The controls were randomly selected and 1:1 matched to the cases on sex, age (±1year), and zoster vaccination (±3 months of the case's vaccination date). Conditional logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Having any blood relative with a history of HZ was associated with a slightly increased risk of HZ (adjusted OR=1.37, 95% CI 1.05-1.79). The adjusted OR associated with having one and two categories of first-degree blood relatives with a history of HZ was 1.30 (95% CI: 0.97-1.73) and 2.53 (95% CI: 1.17-5.44), respectively. Our results suggested a weak association between the development of HZ and a positive family history of HZ among the elderly population. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Vaccination against herpes zoster in developed countries

PubMed Central

Drolet, Mélanie; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Johnson, Robert W.; Patrick, David; Mansi, James A.; Brisson, Marc

2013-01-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine’s duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y. PMID:23324598

Herpes simplex and varicella zoster CNS infections: clinical presentations, treatments and outcomes.

PubMed

Kaewpoowat, Quanhathai; Salazar, Lucrecia; Aguilera, Elizabeth; Wootton, Susan H; Hasbun, Rodrigo

2016-06-01

To describe the clinical manifestations, cerebrospinal fluid (CSF) characteristics, imaging studies and prognostic factors of adverse clinical outcomes (ACO) among adults with herpes simplex virus (HSV) or varicella zoster virus (VZV) CNS infections. Retrospective review of adult patients with positive HSV or VZV polymerase chain reaction on CSF from an observational study of meningitis or encephalitis in Houston, TX (2004-2014), and New Orleans, LA (1999-2008). Ninety-eight adults patients were identified; 25 had encephalitis [20 (20.4 %) HSV, 5 (5.1 %) VZV], and 73 had meningitis [60 (61.1 %) HSV and 13 (13.3 %) VZV]. HSV and VZV had similar presentations except for nausea (P < 0.01) and rash (P < 0.001). The CSF profile did not differ between HSV and VZV infection. Abnormal neuroimaging findings were found in 11.6 % (10/86) brain CTs and 21.3 % (16/75) brain MRIs. The EEG was abnormal in 57.9 % (11/19). Sixteen patients (16.3 %) had an ACO (10 HSV encephalitis, 3 VZV encephalitis and 3 VZV meningitis). Intravenous acyclovir administered within 48 h was protective against an ACO [OR 0.19 (0.04-0.80), P = 0.02). However, on logistic regression only Charlson comorbidity score >1 and an encephalitis presentation were independently associated with an ACO. The treatment for HSV meningitis was variable, and all patients had a good clinical outcome. Alpha herpes CNS infections due to HSV and VZV infections have similar clinical and laboratory manifestations. ACO was observed more frequently in those patients with comorbidities and an encephalitis presentation.

Herpes zoster: Risk and prevention during immunomodulating therapy.

PubMed

Tran, Cong Tri; Ducancelle, Alexandra; Masson, Charles; Lunel-Fabiani, Françoise

2017-01-01

Herpes zoster can be serious or incapacitating, particularly in patients whose immune system is compromised by a disease or treatment. Immunomodulating drugs can increase the risk of infection. Well-established risk factors include advanced age and glucocorticoid therapy. The data are somewhat conflicting for medications such as methotrexate, tofacitinib, TNFα antagonists (infliximab, adalimumab, etanercept, certolizumab, and golimumab), abatacept, tocilizumab, and rituximab. Nevertheless, the risk of herpes zoster is increased in patients taking biological agents, because of the underlying diseases and/or effects of the drugs. A live attenuated herpes zoster vaccine has been proven effective and safe in immunocompetent individuals. At present, however, it is not recommended for patients with immunodeficiencies, including those taking biological drugs, as no studies have assessed its risk/benefit ratio in this population. This situation may change in the near future, as recent data support the effectiveness and safety of the herpes zoster vaccine in patients who take biotherapies or have other causes of immunodeficiency. Alternative approaches designed to protect these patients from herpes zoster and its complications are also under evaluation. There is a need to define the indications of the herpes zoster vaccine in terms of the target population, timing, modalities, and frequency, according to the underlying chronic systemic disease, age group, varicella-zoster virus status, and exposure to therapeutic agents. Copyright © 2016 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.

Serosurveillance of varicella and hepatitis B infection after reported cases in medical students and the relationship between past varicella disease history and immunity status.

PubMed

Suwanpakdee, Detchvijitr; Laohapand, Chalida; Moolasart, Visal; Lomtong, Prasong; Krairojananan, Nat; Srisawat, Phutsapong; Watanaveeradej, Veerachai

2012-05-01

To identify seroprevalence of varicella and the relationship with their histories of experiences of varicella diseases and to provide appropriate immunization against varicella, mumps, measles, rubella and hepatitis B to medical students. All of the medical students were eligible for participation after informed consents. Immunization history against varicella, mumps, measles, rubella (MMR) and hepatitis B were obtained from a questionnaire. A blood sample was obtained from each student for IgG antibody against VZV by ELISA. Medical students with an uncertain history or no documentation of hepatitis B vaccination were tested for HBsAg and anti-HBcIgG by ELISA. There were 383 medical students enrolled. The mean age at enrollment was 21.6 years (median 21.4 years; range 18-25.8 years). Of 383 medical students, 372 (97.2%) had documents of receiving MMR immunizations. The blood samples were obtained from 374 of 383 (97.6%) medical students to identify the immunity against varicella zoster virus (VZV) and the seroprevalence rate was 92%. Using VZVIgG antibody detection as a standard test, history of experience of varicella disease provided positive predictive value of 99.3% (148/149). Of 383 medical students, 277 (72.3%) were tested for hepatitis B markers and 243 (87.7%) students showed negative results. The prevalence of HBsAg carriers was 0.01% (4/383). Suboptimal immunities against vaccine preventable diseases could be demonstrated in the medical students including varicella and hepatitis B. New recommendations of immunizations against varicella, MMR and hepatitis B viruses for a particular group of the population were provided.

Fatal varicella in immigrants from tropical countries: Case reports and forensic perspectives.

PubMed

Guadagnini, Gianni; Lo Baido, Simone; Poli, Francesca; Govi, Annamaria; Borin, Sveva; Fais, Paolo; Pelotti, Susi

2018-05-01

The primary Varicella Zoster Virus (VZV) infection results in varicella, a generally benign, self-limiting disease in immunocompetent children. Despite the usual course a possible fatal evolution of the primary infection is observed predominantly in immunocompromised subjects and in adults, especially emigrating from tropical regions. Two cases of fatal varicella have been investigated and discussed. Death occurred in two patients over 40 years of age, coming from South Asia and receiving chronic immunosuppressive therapy. The forensic expert must be cautious and consider all clinical records in managing fatal varicella cases, bearing in mind risk factors and pre-existing conditions such as age, geographical provenance and pathological comorbidity, which may lead to a bad prognosis irrespective of therapies. Based on the severe and fatal course observed in the reported cases, an extension of the immunization program appears advisable for immigrants from tropical countries, especially before scheduled immunotherapy. Copyright © 2018 Elsevier B.V. All rights reserved.

Simian varicella virus reactivation in cynomolgus monkeys

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mahalingam, Ravi; Traina-Dorge, Vicki; Wellish, Mary

2007-11-10

SVV infection of primates closely resembles VZV infection of humans. Like VZV, SVV becomes latent in ganglionic neurons. We used this model to study the effect of immunosuppression on varicella reactivation. Cynomolgus monkeys latently infected with SVV were irradiated and treated with tacrolimus and prednisone. Of four latently infected monkeys that were immunosuppressed and subjected to the stress of transportation and isolation, one developed zoster, and three others developed features of subclinical reactivation. Another non-immunosuppressed latently infected monkey that was subjected to the same stress of travel and isolation showed features of subclinical reactivation. Virus reactivation was confirmed not onlymore » by the occurrence of zoster in one monkey, but also by the presence of late SVV RNA in ganglia, and the detection of SVV DNA in non-ganglionic tissue, and SVV antigens in skin, ganglia and lung.« less

Eye and Periocular Skin Involvement in Herpes Zoster Infection

PubMed Central

Kalogeropoulos, Chris D.; Bassukas, Ioannis D.; Moschos, Marilita M.; Tabbara, Khalid F.

2015-01-01

Herpes zoster ophthalmicus (HZO) is a clinical manifestation of the reactivation of latent varicella zoster virus (VZV) infection and is more common in people with diminished cell-mediated immunity. Lesions and pain correspond to the affected dermatomes, mostly in first or second trigeminal branch and progress from maculae, papules to vesicles and form pustules, and crusts. Complications are cutaneous, visceral, neurological, ocular, but the most debilitating is post-herpetic neuralgia. Herpes zoster ophthalmicus may affect all the ophthalmic structures, but most severe eye-threatening complications are panuveitis, acute retinal necrosis (ARN) and progressive outer retinal necrosis (PORN) as well. Antiviral medications remain the primary therapy, mainly useful in preventing ocular involvement when begun within 72 hours after the onset of the rash. Timely diagnosis and management of HZO are critical in limiting visual morbidity. Vaccine in adults over 60 was found to be highly effective to boost waning immunity what reduces both the burden of herpes zoster (HZ) disease and the incidence of post-herpetic neuralgia (PHN). PMID:27800502

Vaccines for preventing herpes zoster in older adults.

PubMed

Gagliardi, Anna M Z; Andriolo, Brenda N G; Torloni, Maria R; Soares, Bernardo G O

2016-03-03

Herpes zoster, also known as 'shingles', is a neurocutaneous disease characterised by the reactivation of the latent varicella zoster virus (VZV), the virus that causes chickenpox when immunity to VZV declines. It is an extremely painful condition that can last many weeks or months and it can significantly compromise the quality of life of affected individuals. The natural process of aging is associated with a reduction in cellular immunity and this predisposes older people to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production avoiding viral reactivation. The Food and Drug Administration has approved a herpes zoster vaccine with an attenuated active virus for clinical use among older adults, which has been tested in large populations. A new adjuvanted recombinant VZV subunit zoster vaccine has also been tested. It consists of recombinant VZV glycoprotein E and a liposome-based AS01B adjuvant system. This new vaccine is not yet available for clinical use. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. For this 2015 update, we searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE (1948 to the 3rd week of October 2015), EMBASE (2010 to October 2015), CINAHL (1981 to October 2015) and LILACS (1982 to October 2015). Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also performed 'Risk of bias' assessment. We identified 13 studies involving 69,916 participants. The largest study included 38,546 participants. All studies were conducted in high-income countries and included only healthy Caucasian individuals ≥ 60 years of age without immunosuppressive comorbidities. Ten studies used live attenuated varicella zoster virus (VZV

Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography.

PubMed

Grose, Charles

2012-09-01

The goal of this minireview is to provide an overview of varicella-zoster virus (VZV) phylogenetics and phylogeography when placed in the broad context of geologic time. Planet Earth was formed over 4 billion years ago, and the supercontinent Pangaea coalesced around 400 million years ago (mya). Based on detailed tree-building models, the base of the phylogenetic tree of the Herpesviridae family has been estimated at 400 mya. Subsequently, Pangaea split into Laurasia and Gondwanaland; in turn, Africa rifted from Gondwanaland. Based on available data, the hypothesis of this minireview is that the ancestral alphaherpesvirus VZV coevolved in simians, apes, and hominins in Africa. When anatomically modern humans first crossed over the Red Sea 60,000 years ago, VZV was carried along in their dorsal root ganglia. Currently, there are five VZV clades, distinguishable by single nucleotide polymorphisms. These clades likely represent continued VZV coevolution, as humans with latent VZV infection left Arabia and dispersed into Asia (clades 2 and 5) and Europe (clades 1, 3, and 4). The prototype VZV sequence contains nearly 125,000 bp, divided into 70 open reading frames. Generally, isolates within a clade display >99.9% identity to one another, while members of one clade compared to a second clade show 99.8% identity to one another. Recently, four different VZV genotypes that do not segregate into the previously defined five clades have been identified, a result indicating a wider than anticipated diversity among newly collected VZV strains around the world.

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review.

PubMed

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field.

Herpes Zoster Risk Reduction through Exposure to Chickenpox Patients: A Systematic Multidisciplinary Review

PubMed Central

Ogunjimi, Benson; Van Damme, Pierre; Beutels, Philippe

2013-01-01

Varicella-zoster virus (VZV) causes chickenpox and may subsequently reactivate to cause herpes zoster later in life. The exogenous boosting hypothesis states that re-exposure to circulating VZV can inhibit VZV reactivation and consequently also herpes zoster in VZV-immune individuals. Using this hypothesis, mathematical models predicted widespread chickenpox vaccination to increase herpes zoster incidence over more than 30 years. Some countries have postponed universal chickenpox vaccination, at least partially based on this prediction. After a systematic search and selection procedure, we analyzed different types of exogenous boosting studies. We graded 13 observational studies on herpes zoster incidence after widespread chickenpox vaccination, 4 longitudinal studies on VZV immunity after re-exposure, 9 epidemiological risk factor studies, 7 mathematical modeling studies as well as 7 other studies. We conclude that exogenous boosting exists, although not for all persons, nor in all situations. Its magnitude is yet to be determined adequately in any study field. PMID:23805224

[S1 Herpes zoster localization: acute urinary retention in woman].

PubMed

Vella, Marco; Mastrocinque, Giuseppe; Romeo, Salvatore; Giammanco, Giovanni; Melloni, Darwin

2011-01-01

Acute urinary retention in women is rare. The varicella-zoster virus causes inflammatory lesions of the sensory-root ganglions, meninges and, less frequently, spinal cord. Herpes zoster has been reported to affect, although rarely, lower urinary tract innervations, and acute urinary retention can be thought to occur in the presence of sacral dermatome involvement. Usually it is located in S2-4 dermatome and the prognosis for acute urinary retention is benign resolving in about 20 days. We present a case in which the S1 dermatome was involved and acute urinary retention developed. After 10 days of specific therapy and self-catheterization the problem resolved.

Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

PubMed

Cho, Bum-Joo; Kim, Ji-Soo; Hwang, Jeong-Min

2013-12-01

A 55-year-old woman presented with diplopia following painful skin eruptions on the right upper extremity. On presentation, she was found to have 35 prism diopters of esotropia and an abduction limitation in the left eye. Two weeks later, she developed blepharoptosis and anisocoria with a smaller pupil in the right eye, which increased in the darkness. Cerebrospinal fluid analysis showed pleocytosis and a positive result for immunoglobulin G antibody to varicella zoster virus. She was diagnosed to have zoster meningitis with Horner's syndrome and contralateral abducens nerve palsy. After intravenous antiviral and steroid treatments, the vesicular eruptions and abducens nerve palsy improved. Horner's syndrome and diplopia resolved after six months. Here we present the first report of Horner's syndrome and contralateral abducens nerve palsy associated with zoster meningitis.

Long-term effectiveness of varicella vaccine: a 14-Year, prospective cohort study.

PubMed

Baxter, Roger; Ray, Paula; Tran, Trung N; Black, Steve; Shinefield, Henry R; Coplan, Paul M; Lewis, Edwin; Fireman, Bruce; Saddier, Patricia

2013-05-01

Varicella vaccine was licensed in the United States in 1995 for individuals ≥12 months of age. A second dose was recommended in the United States in June 2006. Varicella incidence and vaccine effectiveness were assessed in a 14-year prospective study conducted at Kaiser Permanente Northern California. A total of 7585 children vaccinated with varicella vaccine in their second year of life in 1995 were followed up prospectively for breakthrough varicella and herpes zoster (HZ) through 2009. A total of 2826 of these children received a second dose in 2006-2009. Incidences of varicella and HZ were estimated and compared with prevaccine era rates. In this cohort of vaccinated children, the average incidence of varicella was 15.9 per 1000 person-years, nine- to tenfold lower than in the prevaccine era. Vaccine effectiveness at the end of the study period was 90%, with no indication of waning over time. Most cases of varicella were mild and occurred early after vaccination. No child developed varicella after a second dose. HZ cases were mild, and rates were lower in the cohort of vaccinated children than in unvaccinated children during the prevaccine era (relative risk: 0.61 [95% confidence interval: 0.43-0.89]). This study confirmed that varicella vaccine is effective at preventing chicken pox, with no waning noted over a 14-year period. One dose provided excellent protection against moderate to severe disease, and most cases occurred shortly after the cohort was vaccinated. The study data also suggest that varicella vaccination may reduce the risks of HZ in vaccinated children.

Detection of herpes simplex virus and varicella-zoster virus in clinical swabs: frequent inhibition of PCR as determined by internal controls.

PubMed

Bezold, G; Volkenandt, M; Gottlöber, P; Peter, R U

2000-12-01

PCR-based detection of microorganisms is widely used for diagnostic purposes. Most routine PCR applications do not control for inhibition of PCR, thus leading to false-negative results. One hundred eighteen swab samples obtained from skin and mucosa were investigated for the presence of herpes simplex virus (HSV), varicella-zoster virus (VZV), and the control gene betaglobin by internally controlled PCR with purified and unpurified DNA in parallel. With unpurified DNA, inhibition of PCR was detected in 23% of betaglobin PCRs, 25% of VZV PCRs, and 16% of HSV PCRs versus 3% each for purified DNA. Approximately 20% of the samples with positive results for HSV or VZV had negative or inhibited results using unpurified DNA. These results indicate that PCR from clinical swab specimens should be performed exclusively with internal controls because the positive control alone cannot exclude PCR inhibition in individual samples. Purification of DNA will decrease, but not exclude, PCR inhibition.

Update on herpes zoster vaccination

PubMed Central

Shapiro, Marla; Kvern, Brent; Watson, Peter; Guenther, Lyn; McElhaney, Janet; McGeer, Allison

2011-01-01

Abstract Objective To answer frequently asked questions surrounding the use of the new herpes zoster (HZ) vaccine. Sources of information Published results of clinical trials and other studies, recommendations from the Canadian National Advisory Committee on Immunization, and the US Advisory Committee on Immunization Practices; data were also obtained from the vaccine’s Health Canada–approved product monograph. Main message Herpes zoster results from reactivation of the varicella-zoster virus; postherpetic neuralgia (PHN) is its most common and serious complication. The incidence of PHN after HZ is directly related to age, with 50% of affected individuals older than 60 years experiencing persistent and unrelieved pain. The live virus HZ vaccine reduces the incidence of HZ by about 50% and the occurrence of PHN by two-thirds, with vaccinated individuals experiencing attenuated or shortened symptoms. The vaccine is contraindicated in many immunocompromised patients and might not be effective in patients taking antiviral medications active against the HZ virus. Physicians should be aware of the different recommendations for these groups. Conclusion The HZ vaccine is a safe and effective preventive measure for reducing the overall burden and severity of HZ in older adults. The vaccine appears to be cost-effective when administered to adults aged 60 years and older. PMID:21998225

Simultaneous Cocirculation of Both European Varicella-Zoster Virus Genotypes (E1 and E2) in Mexico City▿

PubMed Central

Rodríguez-Castillo, Araceli; Vaughan, Gilberto; Ramírez-González, José Ernesto; Escobar-Gutiérrez, Alejandro

2010-01-01

Full-length genome analysis of varicella-zoster virus (VZV) has shown that viral strains can be classified into seven different genotypes: European (E), Mosaic (M), and Japanese (J), and the E and M genotypes can be further subclassified into E1, E2, and M1 through 4, respectively. The distribution of the main VZV genotypes in Mexico was described earlier, demonstrating the predominance of E genotype, although other genotypes (M1 and M4) were also identified. However, no information regarding the circulation of either E genotype in the country is available. In the present study, we confirm the presence of both E1 and E2 genotypes in the country and explore the possibility of coinfection as the triggering factor for increased virulence among severe cases. A total of 61 different European VZV isolates collected in the Mexico City metropolitan area from 2005 to 2006 were typed by using a PCR method based on genotype-specific primer amplification. Fifty isolates belonged to the E1 genotype, and the eleven remaining samples were classified as E2 genotypes. No coinfection with both E genotypes was identified among these specimens. We provide here new information on the distribution of VZV genotypes circulating in Mexico City. PMID:20220168

Pangaea and the Out-of-Africa Model of Varicella-Zoster Virus Evolution and Phylogeography

PubMed Central

2012-01-01

The goal of this minireview is to provide an overview of varicella-zoster virus (VZV) phylogenetics and phylogeography when placed in the broad context of geologic time. Planet Earth was formed over 4 billion years ago, and the supercontinent Pangaea coalesced around 400 million years ago (mya). Based on detailed tree-building models, the base of the phylogenetic tree of the Herpesviridae family has been estimated at 400 mya. Subsequently, Pangaea split into Laurasia and Gondwanaland; in turn, Africa rifted from Gondwanaland. Based on available data, the hypothesis of this minireview is that the ancestral alphaherpesvirus VZV coevolved in simians, apes, and hominins in Africa. When anatomically modern humans first crossed over the Red Sea 60,000 years ago, VZV was carried along in their dorsal root ganglia. Currently, there are five VZV clades, distinguishable by single nucleotide polymorphisms. These clades likely represent continued VZV coevolution, as humans with latent VZV infection left Arabia and dispersed into Asia (clades 2 and 5) and Europe (clades 1, 3, and 4). The prototype VZV sequence contains nearly 125,000 bp, divided into 70 open reading frames. Generally, isolates within a clade display >99.9% identity to one another, while members of one clade compared to a second clade show 99.8% identity to one another. Recently, four different VZV genotypes that do not segregate into the previously defined five clades have been identified, a result indicating a wider than anticipated diversity among newly collected VZV strains around the world. PMID:22761371

Incidence and consequences of varicella in children treated for cancer in Guatemala.

PubMed

Brown, Amy E Caruso; Asturias, Edwin J; Melgar, Mario; Antillon-Klussmann, Federico A; Mettler, Pamela; Levin, Myron J

2016-08-01

Varicella-zoster virus infection is associated with significant morbidity and mortality in immune-compromised children, despite treatment with antiviral agents. Universal varicella vaccine programs have significantly decreased this risk in many highincome countries, but in most low-income and middleincome countries, the burden of varicella in children treated for malignancy is poorly defined. We retrospectively reviewed records of children at the National Unit of Pediatric Oncology (UNOP) in Guatemala diagnosed with varicella between January 2009 and March 2013 in order to calculate incidence of varicella and evaluate morbidity, mortality, treatment interruption, and cost. Fifty-nine cases of varicella were identified. Incidence was 23.4 cases per 1000 person-years (p-y). 66.1% of cases occurred in children with leukemia (median age 5.2 years; interquantile range 3.4-7 years) and 41.0% of these occurred during maintenance therapy. Source of exposure was identified for 14/59 (23.7%) children. Most were hospitalized (71.2%) and given intravenous acyclovir (64.4%). Eight (13.6%) children required critical care, and two (3.4%) died from disseminated varicella with multiorgan failure. Chemotherapy was delayed or omitted due to varicella in 50%. No significant differences in outcomes based on nutritional and immunologic status were detected. The minimum average cost of treatment per episode was 598.75 USD. Varicella is a significant problem in children treated for cancer in Guatemala, where effective post-exposure prophylaxis is limited. In the absence of universal varicella vaccination, strategies to improve recognition of exposure and the future use of novel inactivated vaccines currently under investigation in clinical trials could mitigate this burden.

Epidemiological Study on the Incidence of Herpes Zoster in Nearby Cheonan

PubMed Central

Jung, Ho Soon; Kang, Jin Ku

2015-01-01

Background Herpes Zoster is a disease that occurs after the virus is reactivated due to infection of the varicella virus in childhood. Risk factors are advanced age, malignant neoplasm, organ transplantation, immunosuppressive agents taking are known. The purpose of this study was to investigate the relationship between the seasonal effect and other risk factors on the incidence of herpes zoster. Methods The medical records of 1,105 patients admitted to the outpatient diagnosed with herpes zoster were retrospectively examined. The patients' sex, age, dermatome, onset, underlying disease, residential areas were collected. Results The incidence of women outnumbered men and increased for those above the age of 50. The number of occurrences of herpes zoster patients was higher in the spring and summer than in winter. Unlike men, women had the most frequent outbreaks in March. The most common occurrence of dermatome is in the thoracic region. The number of occurrence was similar on the left as the right. Conclusions In this study, herpes zoster occurs more often in women than in men and more frequently occurs in women in the spring and summer. PMID:26175879

Unusually severe varicella zoster (VZV) virus viral (aseptic) meningitis in an unimmunized, immunocompetent host with chickenpox.

PubMed

Cunha, Burke A; Warren-Favorito, Heather; Mickail, Nardeen

2011-01-01

Chickenpox is caused by the varicella zoster virus (VZV) and may be more severe in adults than in children. Central nervous system (CNS) manifestations of chickenpox and VZV are uncommon, for example, encephalitis and cerebellar ataxis. Viral (aseptic) meningitis is a rare CNS complication of VZV. The cerebrospinal fluid (CSF) profile in VZV viral (aseptic) meningitis is indistinguishable from other causes of viral meningitis. The clue to most of the diagnoses of VZV aseptic meningitis is based on the temporal relationship between antecedent or concomitant chickenpox. Chickenpox is a clinical diagnosis based on the appearance and distribution of the rash. The rash of chickenpox is vesicular/pruritic and typically appears in crops over 3 successive days. VZV vesicles are fragile, superficial, and surrounded by a erythematous halo. Common nonspecific laboratory findings in chickenpox include leukopenia, thrombocytopenia, and elevated serum transaminases (serum glutamate-oxaloacetate transaminase/serum glutamate-pyruvate transaminase). The erythrocyte sedimentation rate (ESR) is not highly elevated in chickenpox. In VZV aseptic meningitis, the CSF shows a lymphocytic pleocytosis with normal protein, glucose, and lactic acid levels. CSF red blood cells are not a feature of VZV meningitis. We present the case of a healthy unimmunized adult who was hospitalized with chickenpox complicated by VZV aseptic meningitis with an unusually severe headache and nuchal rigidity that occurred during hospitalization. Copyright © 2011 Elsevier Inc. All rights reserved.

A model of lytic, latent, and reactivating varicella-zoster virus infections in isolated enteric neurons.

PubMed

Gershon, Anne A; Chen, Jason; Gershon, Michael D

2008-03-01

Because human primary afferent neurons are not readily obtained, we sought to develop a model in which the lytic, latent, and reactivating phases of varicella-zoster virus (VZV) infection were recapitulated in neurons from an animal source. Enteric neurons were obtained from the small intestine of adult guinea pigs and from the bowel of fetal mice. Latency was established when these neurons were infected by cell-free VZV in the absence of fibroblasts or other cells of mesodermal origin. In contrast, lytic infection ensued when fibroblasts were present or when the enteric neurons were infected by cell-associated VZV. Latency was associated with the expression of a limited subset of viral genes, the products of which were restricted to the cytoplasm. Lysis was associated with the expression of viral glycoproteins, nuclear translocation of latency-associated gene products, and rapid cell death. Reactivation was accomplished by expressing VZV open reading frame (ORF) 61p or herpes simplex virus ICP0 in latently infected neurons. Isolated enteric neurons from guinea pigs and mice recapitulate latent gene expression in human cranial nerve and dorsal root ganglia. Expression of latency-associated VZV gene products was detected in 88% of samples of adult human intestine, suggesting that VZV not only infects enteric neurons but also is latent in the human enteric nervous system. This in vitro model should facilitate further understanding of latency and reactivation of VZV.

Human varicella zoster virus is not present in the semen of a man affected by chickenpox during the in vitro fertilisation of his wife.

PubMed

Chan, D Y L; Lam, K K W; Lau, E Y L; Yeung, W S B; Ng, E H Y

2017-12-01

Human varicella zoster virus (VZV) is a member of the herpes virus family and affects humans only. Information about the presence of the virus in the semen samples of men affected by chickenpox is rather limited in the literature. Here, we reported a husband was affected by VZV during in vitro fertilisation treatment of his wife treated in our centre. The semen sample was checked for the presence of VZV by the PCR technique. The PCR result found no detectable viral DNA in the semen sample. The semen sample was then used for conventional IVF insemination and subsequently a healthy baby boy was born. This single case report suggests that the semen sample of men affected by chickenpox may be safe to use for assisted reproduction methods during the VZV infective period. © 2017 Blackwell Verlag GmbH.

Shingrix: The New Adjuvanted Recombinant Herpes Zoster Vaccine.

PubMed

James, Stephanie F; Chahine, Elias B; Sucher, Allana J; Hanna, Cassandra

2018-02-01

To review the immunogenicity, efficacy, and safety of the herpes zoster subunit vaccine (HZ/su) for use in adult patients for the prevention of shingles. A literature search through PubMed was conducted (June 2008 to October 2017) using the terms shingles vaccine and varicella zoster virus. References from retrieved articles and the prescribing information were also reviewed for any additional material. The literature search was limited to human studies published in English. Randomized controlled, multicenter trials were reviewed and included to evaluate the safety and efficacy of HZ/su. Literature on the epidemiology and pathology of herpes zoster virus infections and recommendations from the Advisory Committee on Immunization Practices (ACIP) were also reviewed. HZ/su is a new adjuvanted recombinant vaccine approved by the Food and Drug Administration for the prevention of herpes zoster in adults 50 years of age and older. HZ/su significantly reduced the risk of developing herpes zoster by more than 90% as compared with placebo and displayed a comparable adverse effect profile. The most common local adverse events were injection site pain, redness, and swelling, and the most common systemic adverse events were myalgia, fatigue, and headache. The ACIP recommends the routine use of HZ/su as the preferred vaccine for the prevention of herpes zoster in immunocompetent adults 50 years of age and older. Based on published immunogenicity, efficacy, and safety data, as well as the recent recommendations by the ACIP, HZ/su should be included on both hospital and community pharmacy formularies and recommended to all immunocompetent patients older than 50 years to prevent herpes zoster.

Clinical and economic impact of various strategies for varicella immunity screening and vaccination of health care personnel.

PubMed

Baracco, G J; Eisert, S; Saavedra, S; Hirsch, P; Marin, M; Ortega-Sanchez, I R

2015-10-01

Exposure to patients with varicella or herpes zoster causes considerable disruption to a health care facility's operations and has a significant health and economic impact. However, practices related to screening for immunity and immunization of health care personnel (HCP) for varicella vary widely. A decision tree model was built to evaluate the cost-effectiveness of 8 different strategies of screening and vaccinating HCP for varicella. The outcomes are presented as probability of acquiring varicella, economic impact of varicella per employee per year, and cost to prevent additional cases of varicella. Monte Carlo simulations and 1-way sensitivity analyses were performed to address the uncertainties inherent to the model. Alternative epidemiologic and technologic scenarios were also analyzed. Performing a clinical screening followed by serologic testing of HCP with negative history diminished the cost impact of varicella by >99% compared with not having a program. Vaccinating HCP with negative screen cost approximately $50,000 per case of varicella prevented at the current level of U.S. population immunity, but was projected to be cost-saving at 92% or lower immunity prevalence. Improving vaccine acceptance rates and using highly sensitive assays also optimize cost-effectiveness. Strategies relying on screening and vaccinating HCP for varicella on employment were shown to be cost-effective for health care facilities and are consistent with current national guidelines for varicella prevention. Published by Elsevier Inc.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster.

PubMed

Kim, Choon Kwan; Choi, Youn Mi; Bae, Eunsin; Jue, Mihn Sook; So, Hyung Seok; Hwang, Eung-Soo

2018-01-01

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster.

Reduced NK cell IFN-γ secretion and psychological stress are independently associated with herpes zoster

PubMed Central

Kim, Choon Kwan; Choi, Youn Mi; Bae, Eunsin; Jue, Mihn Sook; So, Hyung Seok

2018-01-01

The pathogenesis of herpes zoster is closely linked to reduced varicella-zoster virus-specific cell-mediated immunity. However, little is known about the interplay between natural killer cells and psychological stress in the pathogenesis of herpes zoster. This study aimed to investigate possible associations among natural killer cells, T cells and psychological stress in herpes zoster. Interferon-gamma secretion from natural killer cell, psychological stress events, stress cognition scale scores and cytomegalovirus-specific cell-mediated immunity were compared between 44 patients with herpes zoster and 44 age- and gender-matched control subjects. A significantly lower median level of interferon-gamma secreted by natural killer cells was observed in patients with a recent diagnosis of herpes zoster than in control subjects (582.7 pg/ml vs. 1783 pg/ml; P = 0.004), whereas cytomegalovirus-specific cell-mediated immunity was not associated with herpes zoster. Psychological stress events and high stress cognition scale scores were significantly associated in patients with herpes zoster (P<0.001 and P = 0.037, respectively). However, reduced interferon-gamma secretion from natural killer cell and psychological stress were not associated. In conclusion, patients with a recent diagnosis of herpes zoster display reduced interferon-gamma secretion from natural killer cells and frequent previous psychological stress events compared with controls. However, reduced natural killer cell activity is not an immunological mediator between psychological stress and herpes zoster. PMID:29466462

PROTECTIVE LEVELS OF VARICELLA-ZOSTER ANTIBODY DID NOT EFFECTIVELY PREVENT CHICKENPOX IN AN X-LINKED AGAMMAGLOBULINEMIA PATIENT.

PubMed

Nobre, Fernanda Aimée; Gonzalez, Isabela Garrido da Silva; de Moraes-Pinto, Maria Isabel; Costa-Carvalho, Beatriz Tavares

2015-01-01

We describe the case of an eight-year-old boy with X-linked agammaglobulinemia who developed mild varicella despite regular intravenous immunoglobulin (IVIG) therapy. He maintained protective antibody levels against varicella and the previous batches of IVIG that he received had adequate varicella-specific IgG levels. The case illustrates that IVIG may not prevent VZV infection.

Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tilden, A.B.; Cauda, R.; Grossi, C.E.

1986-06-01

Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar tomore » those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.« less

Vernet syndrome resulting from varicella zoster virus infection-a very rare clinical presentation of a common viral infection.

PubMed

Ferreira, João; Franco, Ana; Teodoro, Tiago; Coelho, Miguel; Albuquerque, Luísa

2018-03-12

Vernet syndrome is a unilateral palsy of glossopharyngeal, vagus, and accessory nerves. Varicella zoster virus (VZV) infection has rarely been described as a possible cause. A 76-year-old man presented with 1-week-long symptoms of dysphonia, dysphagia, and weakness of the right shoulder elevation, accompanied by a mild right temporal parietal headache with radiation to the ipsilateral ear. Physical examination showed signs compatible with a right XI, X, and XI cranial nerves involvement and also several vesicular lesions in the right ear's concha. He had a personal history of poliomyelitis and chickenpox. Laringoscopy demonstrated right vocal cord palsy. Brain MRI showed thickening and enhancement of right lower cranial nerves and an enhancing nodular lesion in the ipsilateral jugular foramen, in T1 weighted images with gadolinium. Cerebrospinal fluid (CSF) analysis disclosed a mild lymphocytic pleocytosis and absence of VZV-DNA by PCR analysis. Serum VZV IgM and IgG antibodies were positive. The patient had a noticeable clinical improvement after initiation of acyclovir and prednisolone therapy. The presentation of a VZV infection with isolated IX, X, and XI cranial nerves palsy is extremely rare. In our case, the diagnosis of Vernet syndrome as a result of VZV infection was made essentially from clinical findings and supported by analytical and imaging data.

Administrative Data to Explore the Role of Family History as a Risk Factor for Herpes Zoster.

PubMed

Harpaz, Rafael; Dahl, Rebecca M

2018-06-01

We used administrative data to study the impact of family history on the risk of herpes zoster (HZ). Our HZ cases and our HZ family history were both ascertained on the basis of medically attended diagnoses, without reliance on self-report or recall bias. Family history was associated with HZ risk among both siblings and parents. The strength of the association differed when the index child was latently infected with vaccine-strain vs wild-type varicella zoster virus. Copyright © 2018 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

The Glycoprotein B Cytoplasmic Domain Lysine Cluster Is Critical for Varicella-Zoster Virus Cell-Cell Fusion Regulation and Infection

PubMed Central

Arvin, Ann M.; Oliver, Stefan L.

2016-01-01

ABSTRACT The conserved glycoproteins gB and gH-gL are essential for herpesvirus entry and cell-cell fusion induced syncytium formation, a characteristic of varicella-zoster virus (VZV) pathology in skin and sensory ganglia. VZV syncytium formation, which has been implicated in the painful condition of postherpetic neuralgia, is regulated by the cytoplasmic domains of gB (gBcyt) via an immunoreceptor tyrosine-based inhibition motif (ITIM) and gH (gHcyt). A lysine cluster (K894, K897, K898, and K900) in the VZV gBcyt was identified by sequence alignment to be conserved among alphaherpesviruses, suggesting a functional role. Alanine and arginine substitutions were used to determine if the positive charge and susceptibility to posttranslational modifications of these lysines contributed to gB/gH-gL cell-cell fusion. Critically, the positive charge of the lysine residues was necessary for fusion regulation, as alanine substitutions induced a 440% increase in fusion compared to that of the wild-type gBcyt while arginine substitutions had wild-type-like fusion levels in an in vitro gB/gH-gL cell fusion assay. Consistent with these results, the alanine substitutions in the viral genome caused exaggerated syncytium formation, reduced VZV titers (−1.5 log10), and smaller plaques than with the parental Oka (pOka) strain. In contrast, arginine substitutions resulted in syncytia with only 2-fold more nuclei, a −0.5-log10 reduction in titers, and pOka-like plaques. VZV mutants with both an ITIM mutation and either alanine or arginine substitutions had reduced titers and small plaques but differed in syncytium morphology. Thus, effective VZV propagation is dependent on cell-cell fusion regulation by the conserved gBcyt lysine cluster, in addition to the gBcyt ITIM and the gHcyt. IMPORTANCE Varicella-zoster virus (VZV) is a ubiquitous pathogen that causes chickenpox and shingles. Individuals afflicted with shingles risk developing the painful condition of postherpetic

Seroepidemiology of varicella-zoster virus infection in a cosmopolitan city (Erzurum) in the eastern Turkey.

PubMed

Alp, Handan; Altinkaynak, Sevin; Ertekin, Vildan; Kiliçaslan, Buket; Giiraksin, Asuman

2005-04-01

The aim of the study was to determine VZV seroprevalence under age 30 and to identify the relationship of VZV seroprevalence and several sociodemographic characteristics of the study subjects. The results were presented in order to design a strategy for vaccination against varicella-zoster virus (VZV). It was planned to include a total of 568 subjects. The sampling method of 30 clusters recommended for field studies was used for selecting subjects of a predetermined number in the rural and urban areas in eastern Turkey. ELISA method was used to examine the blood samples for VZV seropositivity. Age, gender, place of living, educational level, family size and socioeconomic status was investigated in the study subjects. Positive VZV seroprevalence was detected in 78% of 559 subjects. Seroprevalence increased with age. Seroprevalence was 16.67% at the age of 1 year, subsequently increased to 57.58% at the age of 4 years, 70% at the age of 7 years, 92.31% at the age of 10 years and then remained 86.78-96.36% in subjects over the age of 10 years. No association was found between sociodemographic variables studied and prevalence levels of antibodies except for educational level in the 0-14 year group. These results suggest that the majority of VZV infections occur during the early childhood; the best option to reduce the circulation of wild type VZV in the population would be the immunization of young children. VZV vaccine should be introduced into the routine childhood vaccination programme in Turkey.

Autophagic flux without a block differentiates varicella-zoster virus infection from herpes simplex virus infection.

PubMed

Buckingham, Erin M; Carpenter, John E; Jackson, Wallen; Zerboni, Leigh; Arvin, Ann M; Grose, Charles

2015-01-06

Autophagy is a process by which misfolded and damaged proteins are sequestered into autophagosomes, before degradation in and recycling from lysosomes. We have extensively studied the role of autophagy in varicella-zoster virus (VZV) infection, and have observed that vesicular cells are filled with >100 autophagosomes that are easily detectable after immunolabeling for the LC3 protein. To confirm our hypothesis that increased autophagosome formation was not secondary to a block, we examined all conditions of VZV infection as well as carrying out two assessments of autophagic flux. We first investigated autophagy in human skin xenografts in the severe combined immunodeficiency (SCID) mouse model of VZV pathogenesis, and observed that autophagosomes were abundant in infected human skin tissues. We next investigated autophagy following infection with sonically prepared cell-free virus in cultured cells. Under these conditions, autophagy was detected in a majority of infected cells, but was much less than that seen after an infected-cell inoculum. In other words, inoculation with lower-titered cell-free virus did not reflect the level of stress to the VZV-infected cell that was seen after inoculation of human skin in the SCID mouse model or monolayers with higher-titered infected cells. Finally, we investigated VZV-induced autophagic flux by two different methods (radiolabeling proteins and a dual-colored LC3 plasmid); both showed no evidence of a block in autophagy. Overall, therefore, autophagy within a VZV-infected cell was remarkably different from autophagy within an HSV-infected cell, whose genome contains two modifiers of autophagy, ICP34.5 and US11, not present in VZV.

Cost-effectiveness of a vaccine to prevent herpes zoster and postherpetic neuralgia in older adults.

PubMed

Rothberg, Michael B; Virapongse, Anunta; Smith, Kenneth J

2007-05-15

A vaccine to prevent herpes zoster was recently approved by the United States Food and Drug Administration. We sought to determine the cost-effectiveness of this vaccine for different age groups. We constructed a cost-effectiveness model, based on the Shingles Prevention Study, to compare varicella zoster vaccination with usual care for healthy adults aged >60 years. Outcomes included cost in 2005 US dollars and quality-adjusted life expectancy. Costs and natural history data were drawn from the published literature; vaccine efficacy was assumed to persist for 10 years. For the base case analysis, compared with usual care, vaccination increased quality-adjusted life expectancy by 0.0007-0.0024 quality-adjusted life years per person, depending on age at vaccination and sex. These increases came almost exclusively as a result of prevention of acute pain associated with herpes zoster and postherpetic neuralgia. Vaccination also increased costs by $94-$135 per person, compared with no vaccination. The incremental cost-effectiveness ranged from $44,000 per quality-adjusted life year saved for a 70-year-old woman to $191,000 per quality-adjusted life year saved for an 80-year-old man. For the sensitivity analysis, the decision was most sensitive to vaccine cost. At a cost of $46 per dose, vaccination cost <$50,000 per quality-adjusted life year saved for all adults >60 years of age. Other variables related to the vaccine (duration, efficacy, and adverse effects), postherpetic neuralgia (incidence, duration, and utility), herpes zoster (incidence and severity), and the discount rate all affected the cost-effectiveness ratio by >20%. The cost-effectiveness of the varicella zoster vaccine varies substantially with patient age and often exceeds $100,000 per quality-adjusted life year saved. Age should be considered in vaccine recommendations.

Review of the Persistence of Herpes Zoster Vaccine Efficacy in Clinical Trials.

PubMed

Cook, Stephen J; Flaherty, Dennis K

2015-11-01

The live attenuated herpes zoster vaccine(*) was approved for the prevention of shingles in 2006. Initial Phase III clinical trials proved vaccine efficacy persisted during the study duration; however, assessment of long-term efficacy required additional studies. This article reviews efficacy data for the zoster vaccine that have been published since 2004. It focuses on studies assessing declining vaccine efficacy. MEDLINE, EMBASE, CENTRAL, and CINAHL databases were searched for zoster vaccine efficacy trials. Randomized controlled trials published from 2004 to 2015 were included in the review. Six studies were included in the review. The zoster vaccine reduced the risk of herpes zoster by 51.3% to 72.4% in 2 Phase III trials. Primary and other analyses showed the vaccine was effective at reducing the burden of illness (61.1%), postherpetic neuralgia (66.5%), disease interference on functional status (66.2%), and disease impact on health-related quality of life (55%) compared with placebo. Surveillance studies showed a decrease in vaccine efficacy for reducing the incidence of herpes zoster during follow-up years 3.3 to 7.8 (39.6% relative reduction) and 4.7 to 11.6 (21.1% relative reduction). Initial zoster vaccine efficacy is significant, but declines in post-vaccination years 3 to 11. This raises the question about the need for possible revaccination with the zoster vaccine. Clinicians should consider the declining efficacy when administering the zoster vaccine to patients. Future studies will need to address the impact of the varicella vaccine on the incidence of shingles and whether this impacts the efficacy of the zoster vaccine. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Structure of the Varicella Zoster Virus Thymidylate Synthase Establishes Functional and Structural Similarities as the Human Enzyme and Potentiates Itself as a Target of Brivudine

PubMed Central

Hew, Kelly; Dahlroth, Sue-Li; Veerappan, Saranya; Pan, Lucy Xin; Cornvik, Tobias; Nordlund, Pär

2015-01-01

Varicella zoster virus (VZV) is a highly infectious human herpesvirus that is the causative agent for chicken pox and shingles. VZV encodes a functional thymidylate synthase (TS), which is the sole enzyme that produces dTMP from dUMP de novo. To study substrate binding, the complex structure of TSVZV with dUMP was determined to a resolution of 2.9 Å. In the absence of a folate co-substrate, dUMP binds in the conserved TS active site and is coordinated similarly as in the human encoded TS (TSHS) in an open conformation. The interactions between TSVZV with dUMP and a cofactor analog, raltitrexed, were also studied using differential scanning fluorimetry (DSF), suggesting that TSVZV binds dUMP and raltitrexed in a sequential binding mode like other TS. The DSF also revealed interactions between TSVZV and in vitro phosphorylated brivudine (BVDUP), a highly potent anti-herpesvirus drug against VZV infections. The binding of BVDUP to TSVZV was further confirmed by the complex structure of TSVZV and BVDUP solved at a resolution of 2.9 Å. BVDUP binds similarly as dUMP in the TSHS but it induces a closed conformation of the active site. The structure supports that the 5-bromovinyl substituent on BVDUP is likely to inhibit TSVZV by preventing the transfer of a methylene group from its cofactor and the subsequent formation of dTMP. The interactions between TSVZV and BVDUP are consistent with that TSVZV is indeed a target of brivudine in vivo. The work also provided the structural basis for rational design of more specific TSVZV inhibitors. PMID:26630264

Herpes zoster duplex bilateralis in an immunocompetent adolescent boy: a case report and literature review.

PubMed

Yan, Chen; Laguna, Benjamin A; Marlowe, Lauren E; Keller, Michael D; Treat, James R

2014-01-01

Simultaneous involvement of herpes zoster in multiple dermatomes is uncommon, and even more so in immunocompetent individuals. We report a case wherein a healthy adolescent boy presented with herpes zoster in two distinct dermatomes, raising concern for immunodeficiency, but he was found to be immunocompetent on further testing. A 14-year-old boy with no significant past medical history developed painless vesicular eruptions in two distinct distributions. Varicella zoster virus polymerase chain reaction was positive from unroofed vesicles in both regions. Initial laboratory studies disclosed abnormalities of unknown significance in natural killer (NK) cell percentage and function. The patient was treated with appropriate antiviral therapy. Repeat studies while healthy were not suggestive of an underlying NK cell defect. There are few case reports describing herpes zoster in two or more dermatomes in children. Previously described presentations most commonly occurred in the context of primary immunodeficiency, acquired immunodeficiency, or immunosuppressive medications. Because of the rarity of this presentation in immunocompetent patients, the authors recommend a thorough immune evaluation of all children presenting with isolated multidermatomal zoster. © 2014 Wiley Periodicals, Inc.

Bronchial ulceration as a prognostic indicator for varicella pneumonia: case report and systematic literature review.

PubMed

Inokuchi, Ryota; Nakamura, Kensuke; Sato, Hajime; Shinohara, Kazuaki; Aoki, Yuta; Doi, Kent; Gunshin, Masataka; Ishii, Takeshi; Matsubara, Takehiro; Hiruma, Takahiro; Nakajima, Susumu; Yahagi, Naoki

2013-04-01

Adult varicella pneumonia is a common and serious complication of varicella zoster virus (VZV) infection in pregnant woman and immunocompromised individuals, with mortality rates of 30-50%. The poor prognosis is attributable to very aggressive disease progression and delayed onset of treatment. Here, we present a case of varicella pneumonia in a 69-year-old woman following long-term immunosuppressive treatment for kidney transplant. Respiratory failure developed within 3 d after admission for skin rash, and the patient died 28 d later despite acyclovir and foscarnet treatment. The autopsy showed extensive mucosal airway ulcerations from the pharynx to the main bronchi and numerous VZV-infected cells. We searched PubMed, Web of Science, and EMBASE (1980 through February 2012), as well as several medical report databases created by Japanese healthcare professionals, for all reported cases of varicella pneumonia for which bronchoscopy findings were documented. Twenty-four cases were included and we found that patients with limited or shallow ulcers had favorable outcomes, whereas patients with vast and deep ulcerations had fatal outcomes. These findings indicate that bronchoscopy findings, particularly those showing bronchial involvement, may be useful for evaluating varicella pneumonia. Copyright © 2012 Elsevier B.V. All rights reserved.

Burning mouth syndrome associated with varicella zoster virus.

PubMed

Nagel, Maria A; Gilden, Don

2016-07-05

We present two cases of burning mouth syndrome (BMS)-of 8-month duration in a 61-year-old woman and of 2-year duration in a 63-year-old woman-both associated with increased levels of antivaricella zoster virus (VZV) IgM antibodies in serum and with pain that improved with antiviral treatment. Combined with our previous finding of BMS due to herpes simplex virus type 1 (HSV-1) infection, we recommend evaluation of patients with BMS not only for VZV or HSV-1 DNA in the saliva, but also for serum anti-VZV and anti-HSV-1 IgM antibodies. Both infections are treatable with oral antiviral agents. 2016 BMJ Publishing Group Ltd.

Vaccination against herpes zoster in developed countries: state of the evidence.

PubMed

Drolet, Mélanie; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Johnson, Robert W; Patrick, David; Mansi, James A; Brisson, Marc

2013-05-01

Although progress has been made in the treatment of herpes zoster (HZ) and postherpetic neuralgia (PHN), available therapeutic options are only partially effective. Given evidence that a live-attenuated varicella-zoster-virus vaccine is effective at reducing the incidence of HZ, PHN and the burden of illness, policymakers and clinicians are being asked to make recommendations regarding the use of the zoster vaccine. In this report, we summarize the evidence regarding the: (1) burden of illness; (2) vaccine efficacy and safety; and (3) cost-effectiveness of vaccination, to assist evidence-based policy making and guide clinicians in their recommendations. First, there is general agreement that the overall burden of illness associated with HZ and PHN is substantial. Second, the safety and efficacy of the zoster vaccine at reducing the burden of illness due to HZ and the incidence of PHN have been clearly demonstrated in large placebo-controlled trials. However, uncertainty remains about the vaccine's duration of protection. Third, vaccination against HZ is likely to be cost-effective when the vaccine is given at approximately 65 y of age, if vaccine duration is longer than 10 y.

Incidence of varicella zoster virus infections of the central nervous system in the elderly: a large tertiary hospital-based series (2007-2014).

PubMed

Arruti, M; Piñeiro, L D; Salicio, Y; Cilla, G; Goenaga, M A; López de Munain, A

2017-06-01

The aim of the study was to describe the clinical and epidemiological characteristics of the central nervous system (CNS) infection by varicella zoster virus (VZV) in patients older than 65 years in a tertiary community hospital. We retrospectively analysed the results of cerebrospinal fluid (CSF) testing in patients older than 65 years between 2007 and 2014 with clinically suspected VZV infection with CNS involvement. Patients whose CSF samples were positive for VZV DNA were included, as were those with negative results who simultaneously presented herpes zoster and CSF or magnetic resonance imaging findings suggestive of CNS infection, and in whom other possible aetiologies had been ruled out. The study included 280 patients. The disease was considered to be caused by a VZV infection in 32 patients (11.4%), of which 23 cases were virologically confirmed (detection of VZV DNA in CSF). The most frequent diagnosis of the patients with VZV CNS infection was encephalitis (83.3%), followed by meningitis (13.3%) and cerebellitis (3.3%). The mean annual incidence of VZV CNS infection was 3.0 cases per 100,000 inhabitants. VZV was the most common cause of encephalitis and viral meningitis, ahead of herpes simplex virus (n = 9). At the time of discharge, 12 (40%) patients showed neurological sequelae. Five patients (20%) died during hospitalization, all with encephalitis. Patients with a fatal outcome had significantly higher median age and longer delay before initiating acyclovir. In conclusion, VZV was the first cause of encephalitis in our elderly population. Despite acyclovir treatment, there was a high rate of case fatality and sequelae at discharge.

Safety and immunogenicity of inactivated varicella-zoster virus vaccine in adults with hematologic malignancies receiving treatment with anti-CD20 monoclonal antibodies.

PubMed

Parrino, Janie; McNeil, Shelly A; Lawrence, Steven J; Kimby, Eva; Pagnoni, Marco F; Stek, Jon E; Zhao, Yanli; Chan, Ivan S F; Kaplan, Susan S

2017-03-27

Immunocompromised patients can experience significant morbidity and occasional mortality from complications associated with herpes zoster (HZ), but live attenuated HZ vaccine is contraindicated for these patients. Inactivated zoster vaccine (ZV IN ) is in development for prevention of HZ in immunocompromised patients. However, there are limited data in the literature regarding the effect of anti-CD20 monoclonal antibodies on vaccine-related cell-mediated immune response. This study evaluated safety and immunogenicity of ZV IN in patients with hematologic malignancies (HM) receiving anti-CD20 monoclonal antibodies (alone or in combination chemotherapy regimens) and not likely to undergo hematopoietic cell transplant (HCT) (n=80). This was an open-label, single-arm, multicenter Phase I study (NCT01460719) of a 4-dose ZV IN regimen (∼30days between doses) in patients ⩾18years old. Blood samples were collected prior to dose 1 and 28days Postdose 4 to measure varicella zoster virus (VZV)-specific T-cell responses using interferon-γ enzyme-linked immunospot (IFN-γ ELISPOT). The primary hypothesis was that ZV IN would elicit significant VZV-specific immune responses at ∼28days Postdose 4, with a geometric fold rise (GMFR) >1.0. All vaccinated patients were evaluated for adverse events (AE) through 28days Postdose 4. ZV IN elicited a statistically significant VZV-specific immune response measured by IFN-γ ELISPOT at 28days Postdose 4 (GMFR=4.34 [90% CI:3.01, 6.24], p-value<0.001), meeting the pre-specified success criterion. Overall, 85% (68/80) of patients reported ⩾1 AE, 44% (35/80) reported ⩾1 injection-site AE, and 74% (59/80) reported ⩾1 systemic AE. The majority of systemic AEs were non-serious and considered unrelated to vaccination by the investigator. Frequencies of AEs did not increase with subsequent doses of vaccine. No recipient of ZV IN had rash polymerase chain reaction (PCR) positive for VZV vaccine strain. In adults with HM receiving anti

An In Vitro Model of Latency and Reactivation of Varicella Zoster Virus in Human Stem Cell-Derived Neurons

PubMed Central

Markus, Amos; Lebenthal-Loinger, Ilana; Yang, In Hong; Kinchington, Paul R.; Goldstein, Ronald S.

2015-01-01

Varicella zoster virus (VZV) latency in sensory and autonomic neurons has remained enigmatic and difficult to study, and experimental reactivation has not yet been achieved. We have previously shown that human embryonic stem cell (hESC)-derived neurons are permissive to a productive and spreading VZV infection. We now demonstrate that hESC-derived neurons can also host a persistent non-productive infection lasting for weeks which can subsequently be reactivated by multiple experimental stimuli. Quiescent infections were established by exposing neurons to low titer cell-free VZV either by using acyclovir or by infection of axons in compartmented microfluidic chambers without acyclovir. VZV DNA and low levels of viral transcription were detectable by qPCR for up to seven weeks. Quiescently-infected human neuronal cultures were induced to undergo renewed viral gene and protein expression by growth factor removal or by inhibition of PI3-Kinase activity. Strikingly, incubation of cultures induced to reactivate at a lower temperature (34°C) resulted in enhanced VZV reactivation, resulting in spreading, productive infections. Comparison of VZV genome transcription in quiescently-infected to productively-infected neurons using RNASeq revealed preferential transcription from specific genome regions, especially the duplicated regions. These experiments establish a powerful new system for modeling the VZV latent state, and reveal a potential role for temperature in VZV reactivation and disease. PMID:26042814

RNA-seq Analysis of Host and Viral Gene Expression Highlights Interaction between Varicella Zoster Virus and Keratinocyte Differentiation

PubMed Central

Singh, Manuraj; Kanda, Ravinder K.; Yee, Michael B.; Kellam, Paul; Hollinshead, Michael; Kinchington, Paul R.; O'Toole, Edel A.; Breuer, Judith

2014-01-01

Varicella zoster virus (VZV) is the etiological agent of chickenpox and shingles, diseases characterized by epidermal skin blistering. Using a calcium-induced keratinocyte differentiation model we investigated the interaction between epidermal differentiation and VZV infection. RNA-seq analysis showed that VZV infection has a profound effect on differentiating keratinocytes, altering the normal process of epidermal gene expression to generate a signature that resembles patterns of gene expression seen in both heritable and acquired skin-blistering disorders. Further investigation by real-time PCR, protein analysis and electron microscopy revealed that VZV specifically reduced expression of specific suprabasal cytokeratins and desmosomal proteins, leading to disruption of epidermal structure and function. These changes were accompanied by an upregulation of kallikreins and serine proteases. Taken together VZV infection promotes blistering and desquamation of the epidermis, both of which are necessary to the viral spread and pathogenesis. At the same time, analysis of the viral transcriptome provided evidence that VZV gene expression was significantly increased following calcium treatment of keratinocytes. Using reporter viruses and immunohistochemistry we confirmed that VZV gene and protein expression in skin is linked with cellular differentiation. These studies highlight the intimate host-pathogen interaction following VZV infection of skin and provide insight into the mechanisms by which VZV remodels the epidermal environment to promote its own replication and spread. PMID:24497829

Real World Evidence for Regulatory Decisions: Concomitant Administration of Zoster Vaccine Live and Pneumococcal Polysaccharide Vaccine.

PubMed

Bruxvoort, Katia; Sy, Lina S; Luo, Yi; Tseng, Hung Fu

2018-04-11

The US Food and Drug Administration is charged with expanding the use of real world evidence (RWE) for regulatory decisions. As a test case for RWE to support regulatory decisions, we present the scenario of concomitant vaccination with zoster vaccine live (ZVL) and 23-valent pneumococcal polysaccharide vaccine (PPSV23). The prescribing information states that these vaccines should not be given concurrently, based on a small trial using varicella zoster virus antibody levels as a correlate of ZVL efficacy, even though ZVL protects against herpes zoster via cell-mediated immunity. We conducted an observational cohort study involving >30,000 members of Kaiser Permanente Southern California receiving concomitant ZVL and PPSV23 versus PPSV23 prior to ZVL. Occurrence of herpes zoster was assessed through electronic health records from January 1, 2007 to June 30, 2016. The adjusted hazard ratio comparing incidence rates of herpes zoster in the concomitant vaccination cohort and the prior vaccination cohort was 1.04 (95% CI: 0.92, 1.16). This RWE study provides direct evidence for a lack of vaccine interference, relying on herpes zoster occurrence rather than an intermediate marker of immunity. RWE is essential for regulators and policy makers in addressing evidentiary gaps regarding safety, effectiveness, compliance, and vaccine interactions for the new recombinant zoster vaccine.

Phosphorylation of varicella-zoster virus glycoprotein gpI by mammalian casein kinase II and casein kinase I

DOE Office of Scientific and Technical Information (OSTI.GOV)

Grose, C.; Jackson, W.; Traugh, J.A.

1989-09-01

Varicella-zoster virus (VZV) glycoprotein gpI is the predominant viral glycoprotein within the plasma membranes of infected cells. This viral glycoprotein is phosphorylated on its polypeptide backbone during biosynthesis. In this report, the authors investigated the protein kinases which participate in the phosphorylation events. Under in vivo conditions, VZV gpI was phosphorylated on its serine and threonine residues by protein kinases present within lysates of either VZV-infected or uninfected cells. Because this activity was diminished by heparin, a known inhibitor of casein kinase II, isolated gpI was incubated with purified casein kinase II and shown to be phosphorylated in an inmore » vitro assay containing ({gamma}-{sup 32}P)ATP. The same glycoprotein was phosphorylated when ({sup 32}P)GTP was substituted for ({sup 32}P)ATP in the protein kinase assay. They also tested whether VZV gpI was phosphorylated by two other ubiquitous mammalian protein kinases--casein kinase I and cyclic AMP-dependent kinase--and found that only casein kinase I modified gpI. When the predicted 623-amino-acid sequence of gpI was examined, two phosphorylation sites known to be optimal for casein kinase II were observed. In summary, this study showed that VZV gpI was phosphorylated by each of two mammalian protein kinases (casein kinase I and casein kinase II) and that potential serine-threonine phosphorylation sites for each of these two kinases were present in the viral glycoprotein.« less

Open Reading Frame S/L of Varicella-Zoster Virus Encodes a Cytoplasmic Protein Expressed in Infected Cells

PubMed Central

Kemble, George W.; Annunziato, Paula; Lungu, Octavian; Winter, Ruth E.; Cha, Tai-An; Silverstein, Saul J.; Spaete, Richard R.

2000-01-01

We report the discovery of a novel gene in the varicella-zoster virus (VZV) genome, designated open reading frame (ORF) S/L. This gene, located at the left end of the prototype VZV genome isomer, expresses a polyadenylated mRNA containing a splice within the 3′ untranslated region in virus-infected cells. Sequence analysis reveals significant differences between the ORF S/Ls of wild-type and attenuated strains of VZV. Antisera raised to a bacterially expressed portion of ORF S/L reacted specifically with a 21-kDa protein synthesized in cells infected with a VZV clinical isolate and with the original vaccine strain of VZV (Oka-ATCC). Cells infected with other VZV strains, including a wild-type strain that has been extensively passaged in tissue culture and commercially produced vaccine strains of Oka, synthesize a family of proteins ranging in size from 21 to 30 kDa that react with the anti-ORF S/L antiserum. MeWO cells infected with recombinant VZV harboring mutations in the C-terminal region of the ORF S/L gene lost adherence to the stratum and adjacent cells, resulting in an altered plaque morphology. Immunohistochemical analysis of VZV-infected cells demonstrated that ORF S/L protein localizes to the cytoplasm. ORF S/L protein was present in skin lesions of individuals with primary or reactivated infection and in the neurons of a dorsal root ganglion during virus reactivation. PMID:11070031

Inhibition of Bim Enhances Replication of Varicella-Zoster Virus and Delays Plaque Formation in Virus-Infected Cells

PubMed Central

Liu, XueQiao

2014-01-01

Programmed cell death (apoptosis) is an important host defense mechanism against intracellular pathogens, such as viruses. Accordingly, viruses have evolved multiple mechanisms to modulate apoptosis to enhance replication. Varicella-zoster virus (VZV) induces apoptosis in human fibroblasts and melanoma cells. We found that VZV triggered the phosphorylation of the proapoptotic proteins Bim and BAD but had little or no effect on other Bcl-2 family members. Since phosphorylation of Bim and BAD reduces their proapoptotic activity, this may prevent or delay apoptosis in VZV-infected cells. Phosphorylation of Bim but not BAD in VZV-infected cells was dependent on activation of the MEK/extracellular signal-regulated kinase (ERK) pathway. Cells knocked down for Bim showed delayed VZV plaque formation, resulting in longer survival of VZV-infected cells and increased replication of virus, compared with wild-type cells infected with virus. Conversely, overexpression of Bim resulted in earlier plaque formation, smaller plaques, reduced virus replication, and increased caspase 3 activity. Inhibition of caspase activity in VZV-infected cells overexpressing Bim restored levels of virus production similar to those seen with virus-infected wild-type cells. Previously we showed that VZV ORF12 activates ERK and inhibits apoptosis in virus-infected cells. Here we found that VZV ORF12 contributes to Bim and BAD phosphorylation. In summary, VZV triggers Bim phosphorylation; reduction of Bim levels results in longer survival of VZV-infected cells and increased VZV replication. PMID:24227856

Intracellular localization of varicella-zoster virus ORF39 protein and its functional relationship to glycoprotein K

DOE Office of Scientific and Technical Information (OSTI.GOV)

Govero, Jennifer; Hall, Susan; Heineman, Thomas C.

2007-02-20

Varicella-zoster virus (VZV) encodes two multiply inserted membrane proteins, open reading frame (ORF) 39 protein (ORF39p) and glycoprotein K (gK). The HSV-1 homologs of these proteins are believed to act in conjunction with each other during viral egress and cell-cell fusion, and they directly influence each other's intracellular trafficking. However, ORF39p and VZV gK have received very limited study largely due to difficulties in producing antibodies to these highly hydrophobic proteins. To overcome this obstacle, we introduced epitope tags into both ORF39p and gK and examined their intracellular distributions in transfected and infected cells. Our data demonstrate that both ORF39pmore » and gK accumulate predominately in the ER of cultured cells when expressed in the absence of other VZV proteins or when coexpressed in isolation from other VZV proteins. Therefore, the transport of VZV ORF39p and gK does not exhibit the functional interdependence seen in their HSV-1 homologs. However, during infection, the primary distributions of ORF39p and gK shift from the ER to the Golgi, and they are also found in the plasma membrane indicating that their intracellular trafficking during infection depends on other VZV-encoded proteins. During infection, ORF39p and gK tightly colocalize with VZV envelope glycoproteins B, E and H; however, the coexpression of ORF39p or gK with other individual viral glycoproteins is insufficient to alter the transport of either ORF39p or gK.« less

Global Identification of Three Major Genotypes of Varicella-Zoster Virus: Longitudinal Clustering and Strategies for Genotyping

PubMed Central

Loparev, Vladimir N.; Gonzalez, Antonio; Deleon-Carnes, Marlene; Tipples, Graham; Fickenscher, Helmut; Torfason, Einar G.; Schmid, D. Scott

2004-01-01

By analysis of a single, variable, and short DNA sequence of 447 bp located within open reading frame 22 (ORF22), we discriminated three major varicella-zoster virus (VZV) genotypes. VZV isolates from all six inhabited continents that showed nearly complete homology to ORF22 of the European reference strain Dumas were assigned to the European (E) genotype. All Japanese isolates, defined as the Japanese (J) genotype, were identical in the respective genomic region and proved the most divergent from the E strains, carrying four distinct variations. The remaining isolates carried a combination of E- and J-specific variations in the target sequence and thus were collectively termed the mosaic (M) genotype. Three hundred twenty-six isolates collected in 27 countries were genotyped. A distinctive longitudinal distribution of VZV genotypes supports this approach. Among 111 isolates collected from European patients, 96.4% were genotype E. Consistent with this observation, approximately 80% of the VZV strains from the United States were also genotype E. Similarly, genotype E viruses were dominant in the Asian part of Russia and in eastern Australia. M genotype viruses were strongly dominant in tropical regions of Africa, Indochina, and Central America, and they were common in western Australia. However, genotype M viruses were also identified as a minority in several countries worldwide. Two major intertypic variations of genotype M strains were identified, suggesting that the M genotype can be further differentiated into subgenotypes. These data highlight the direction for future VZV genotyping efforts. This approach provides the first simple genotyping method for VZV strains in clinical samples. PMID:15254207

Risk of depressive disorder among patients with herpes zoster: a nationwide population-based prospective study.

PubMed

Chen, Mu-Hong; Wei, Han-Ting; Su, Tung-Ping; Li, Cheng-Ta; Lin, Wei-Chen; Chang, Wen-Han; Chen, Tzeng-Ji; Bai, Ya-Mei

2014-05-01

Herpes zoster results from reactivation of the endogenous varicella zoster virus infection. Previous studies have shown that herpes zoster and postherpetic neuralgia were associated with anxiety, depression, and insomnia. However, no prospective study has investigated the association between herpes zoster and the development of depressive disorder. Subjects were identified through the Taiwan National Health Insurance Research Database. Patients 18 years or older with a diagnosis of herpes zoster and without a psychiatric history were enrolled in 2000 and compared with age-/sex-matched controls (1:4). These participants were followed up to the end of 2010 for new-onset depressive disorder. A total of 1888 patients with herpes zoster were identified and compared with 7552 age-/sex-matched controls in 2000. Those with herpes zoster had a higher incidence of developing major depression (2.2% versus 1.4%, p = .018) and any depressive disorder (4.3% versus 3.2%, p = .020) than did the control group. The follow-up showed that herpes zoster was an independent risk factor for major depression (hazard ratio = 1.49, 95% confidence interval = 1.04-2.13) and any depressive disorder (hazard ratio = 1.32, 95% confidence interval = 1.03-1.70), after adjusting demographic data and comorbid medical diseases. This is the first study to investigate the temporal association between herpes zoster and depressive disorder. Further studies would be required to clarify the underlying pathophysiology about this association and whether proper treatment of herpes zoster could decrease the long-term risk of depressive disorder.

HIV-positive patient with herpes zoster: a manifestation of the immune reconstitution inflammatory syndrome.

PubMed

Lutwak, Nancy; Dill, Curt

2012-01-01

Herpes zoster is a common illness that can lead to serious morbidity. There is now evidence that HIV-infected patients who have been treated with antiretroviral therapy are at greater risk of developing herpes zoster not when they are severely immunocompromised but, paradoxically, when their immune system is recovering. This is a manifestation of the immune reconstitution inflammatory syndrome. The objectives of this report are to (1) inform health care providers that HIV-infected patients may develop multiple infectious, autoimmune, and oncological manifestations after treatment with antiretroviral medication, as they have immune system reconstitution, and (2) discuss herpes zoster, one of the possible manifestations. The patient is a 68-year-old HIV-positive man who presented with herpes zoster after being treated with highly active antiretroviral therapy (HAART) when his immune system was recovering, not when he was most immunosuppressed. Emergency department physicians should be aware that HIV-infected patients treated with HAART may have clinical deterioration despite immune system strengthening. This immune reconstitution inflammatory syndrome can present with infectious, autoimmune, or oncological manifestations. Our case patient, an HIV-positive man with immune system recovery after treatment with HAART, presented with an infectious manifestation, herpes zoster.

Dynamic response of airborne infections to climate change: predictions for varicella

NASA Astrophysics Data System (ADS)

Baker, R.; Mahmud, A. S.; Metcalf, C. J. E.

2017-12-01

Characterizing how climate change will alter the burden of infectious diseases has clear applications for public health policy. Despite our uniquely detailed understanding of the transmission process for directly transmitted infections, the impact of climate variables on these infections remains understudied. We develop a novel methodology for estimating the causal relationship between climate and directly transmitted infections, which combines an epidemiological model of disease transmission with panel regression techniques. Our method allows us to move beyond correlational approaches to studying the link between climate and infectious diseases. Further, we can generate semi-mechanistic projections of incidence across climate scenarios. We illustrate our approach using 30 years of reported cases of varicella, a common airborne childhood infection, across 32 states in Mexico. We find significantly increased varicella transmission in drier conditions. We use this to map potential changes in the magnitude and variability of varicella incidence in Mexico as a result of projected changes in future climate conditions. Our results indicate that the predicted decrease in humidity in Mexico towards the end of the century will increase incidence of varicella, all else equal, and that these changes in incidence will be non-uniform across the year.

Three-Dimensional Normal Human Neural Progenitor Tissue-Like Assemblies: A Model for Persistent Varicell-Zoster Virus Infection and Platform to Study Viral Infectivity and Oxidative Stress and Damage

NASA Technical Reports Server (NTRS)

Goodwin, T. J.; McCarthy, M.; Osterrieder, N.; Cohrs, R. J.; Kaufer, B. B.

2014-01-01

The environment of space results in a multitude of challenges to the human physiology that present barriers to extended habitation and exploration. Over 40 years of investigation to define countermeasures to address space flight adaptation has left gaps in our knowledge regarding mitigation strategies partly due to the lack of investigative tools, monitoring strategies, and real time diagnostics to understand the central causative agent(s) responsible for physiologic adaptation and maintaining homeostasis. Spaceflight-adaptation syndrome is the combination of space environmental conditions and the synergistic reaction of the human physiology. Our work addresses the role of oxidative stress and damage (OSaD) as a negative and contributing Risk Factor (RF) in the following areas of combined spaceflight related dysregulation: i) radiation induced cellular damage [1], [2] ii) immune impacts and the inflammatory response [3], [4] and iii) varicella zoster virus (VZV) reactivation [5]. Varicella-zoster (VZV)/Chicken Pox virus is a neurotropic human alphaherpesvirus resulting in varicella upon primary infection, suppressed by the immune system becomes latent in ganglionic neurons, and reactivates under stress events to re-express in zoster and possibly shingles. Our laboratory has developed a complex threedimensional (3D) normal human neural tissue model that emulates several characteristics of the human trigeminal ganglia (TG) and allows the study of combinatorial experimentation which addresses, simultaneously, OSaD associated with Spaceflight adaptation and habitation [6].

Effects of Shield1 on the viral replication of varicella-zoster virus containing FKBP-tagged ORF4 and 48

PubMed Central

Li, Shuying; Liu, Zhanjun; Li, Ji; Liu, Aihua; Zhu, Lihua; Yu, Kui; Zhang, Ke

2018-01-01

The present study aimed to explore the effects of a stabilizing ligand, Shield-1, on the replication of recombinant varicella-zoster virus (VZV) containing FK506 binding protein (FKPB) tags in essential open reading frames (ORF) 4 and 48. A specific galactokinase (galK) selection method was conducted, following the addition of galK labels to VZV ORF4 and 48, using a SW102 VZV bacterial artificial chromosome (BAC) system. Subsequently, recombinant VZV containing FKPB tags in ORF4 and 48 was constructed by counterselection and homologous recombination. Recombinant viral plasmids containing FKPB-tagged VZV ORF4 and 48 were extracted and transfected into human acute retinal pigment epithelial ARPE-19 cells. The results demonstrated that the FKPB-tagged viral protein was rapidly degraded by proteases in recombinant virus-infected ARPE-19 cells. In addition, the recombinant VZVORF4-FKBP-ORF48-FKBP virus could not grow if a synthetic ligand of FKBP, Shield1, was not added to the ARPE-19 cell culture medium; however, the degradation of FKPB-tagged viral protein was prevented if Shield1 was added to the ARPE-19 cell culture medium, thereby allowing viral replication in ARPE-19 cells. These results indicated that Shield1 may regulate replication of recombinant VZVORF4-FKBP-ORF48-FKBP following transfection into human epithelial cells. PMID:29115621

The Varicella-zoster virus DNA encapsidation genes: Identification and characterization of the putative terminase subunits

PubMed Central

Visalli, Robert J.; Nicolosi, Denise M.; Irven, Karen L.; Goshorn, Bradley; Khan, Tamseel; Visalli, Melissa A.

2007-01-01

The putative DNA encapsidation genes encoded by open reading frames (ORFs) 25, 26, 30, 34, 43, 45/42 and 54 were cloned from Varicella-zoster virus (VZV) strain Ellen. Sequencing revealed that the Ellen ORFs were highly conserved at the amino acid level when compared to those of nineteen previously published VZV isolates. Additionally, RT-PCR provided the first evidence that ORF45/42 was expressed as a spliced transcript in VZV-infected cells. All seven ORFs were expressed in vitro and full length products were identified using a C-terminal V5 epitope tag. The in vitro products of the putative VZV terminase subunits encoded by ORFs 30 and 45/42 proved useful in protein-protein interaction assays. Previous studies have reported the formation of a heterodimeric terminase complex involved in DNA encapsidation for both herpes simplex virus-type 1 (HSV-1) and human cytomegalovirus (HCMV). Here we report that the C-terminal portion of exon II of ORF45/42 (ORF42-C269) interacted in GST-pull down experiments with in vitro synthesized ORF30 and ORF45/42. The interactions were maintained in the presence of anionic detergents and in buffers of increasing ionic strength. Cells transiently transfected with epitope tagged ORF45/42 or ORF30 showed primarily cytoplasmic staining. In contrast, an antiserum directed to the N-terminal portion of ORF45 showed nearly exclusive nuclear localization of the ORF45/42 gene product in infected cells. An ORF30 specific antiserum detected an 87 kDa protein in both the cytoplasmic and nuclear fractions of VZV infected cells. The results were consistent with the localization and function of herpesviral terminase subunits. This is the first study aimed at the identification and characterization of the VZV DNA encapsidation gene products. PMID:17868947

Further characterisation of a rat model of varicella zoster virus (VZV)-associated pain

PubMed Central

Hasnie, F. S.; Breuer, J.; Parker, S.; Wallace, V.; Blackbeard, J.; Lever, I.; Kinchington, P.R.; Dickenson, A. H.; Pheby, T.; Rice, A. S. C.

2007-01-01

Persistent herpes zoster-associated pain is a significant clinical problem and an area of largely unmet therapeutic need. Progress in elucidating the underlying pathophysiology of zoster-associated pain and related co-morbidity behaviour, in addition to appropriately targeted drug development has been hindered by the lack of an appropriate animal model. This study further characterises a recently developed rat model of zoster-associated hypersensitivity and investigates (a) response to different viral strains; (b) relationship between viral inoculum concentration (‘dose’) and mechanical hypersensitivity (‘response’); (c) attenuation of virus-associated mechanical hypersensitivity by clinically useful analgesic drugs; and (d) measurement of pain co-morbidity (anxiety-like behaviour) and pharmacological intervention in the open field paradigm (in parallel with models of traumatic peripheral nerve injury). VZV was propagated on fibroblast cells before subcutaneous injection into the glabrous footpad of the left hind limb of adult male Wistar rats. Control animals received injection of uninfected fibroblast cells. Hind-limb reflex withdrawal thresholds to mechanical, noxious thermal and cooling stimuli were recorded at specified intervals post-infection. Infection with all viral strains was associated with a dose-dependent mechanical hypersensitivity but not a thermal or cool hypersensitivity. Systemic treatment with intraperitoneal (i.p.) morphine (2.5mg/kg), amitriptyline (10mg/kg), gabapentin (30mg/kg), (S)-(+)-ibuprofen (20mg/kg) and the cannnabinoid WIN55,212-2 (2mg/kg) but not the antiviral, acyclovir (50mg/kg), was associated with a reversal of mechanical paw withdrawal thresholds. In the open field paradigm, virus-infected and nerve-injured animals demonstrated an anxiety-like pattern of ambulation (reduced entry into the central area of the open arena) which was positively correlated with mechanical hypersensitivity. This may reflect pain

Incidence and clinical features of herpes simplex viruses (1 and 2) and varicella-zoster virus infections in an adult Korean population with aseptic meningitis or encephalitis.

PubMed

Choi, Rihwa; Kim, Gyeong-Moon; Jo, Ik Joon; Sim, Min Seob; Song, Keun Jeong; Kim, Byoung Joon; Na, Duk L; Huh, Hee Jae; Kim, Jong-Won; Ki, Chang-Seok; Lee, Nam Yong

2014-06-01

Since there are limited data on the incidence and clinical findings of central nervous system (CNS) infection by three α-herpesviruses including human herpes simplex virus 1 (HSV-1), HSV-2 and varicella-zoster virus (VZV) in Korea, a retrospective analysis of clinical data and polymerase chain reaction (PCR) results was performed in patients who presented with suspicion of acute viral meningitis and/or encephalitis at the emergency department of a tertiary referral hospital in Seoul, Korea. During the 3-year study period, a total of 224 cerebrospinal fluid (CSF) samples from 224 patients were examined. Among the 224 patients, 135 (60.3%) patients were identified as having aseptic meningitis (n = 70, 51.9%), encephalitis (n = 41, 30.4%) or meningoencephalitis (n = 24, 17.8%) at discharge. Twenty-four (17.8%) patients were identified as having VZV meningitis (n = 16, 11.9%), VZV meningoencephalitis (n = 2, 1.5%), HSV-2 meningitis (n = 4, 3.0%), or HSV-1 encephalitis (n = 2, 1.5%). Of the 24 patients infected with the three herpesviruses, immunocompromised patients accounted for 33.3% (n = 8). Skin rashes were observed in half (n = 9) of the patients with VZV, and none with HSV-1 or HSV-2. One patient with VZV meningitis and four patients with brain parenchymal involvement had neurologic sequelae. In conclusion, three herpesviruses are important causative agents of CNS infectious disease with significant morbidity in adults, regardless of the immunologic status. Therefore, CSF should be examined for HSV-1, HSV-2, and VZV using sensitive diagnostic methods in all cases of adult patients with clinical manifestations of CNS disease in order to identify the correct etiology and to determine appropriate therapy. © 2014 Wiley Periodicals, Inc.

Reactivation of herpes zoster keratitis in an adult after varicella zoster vaccination.

PubMed

Hwang, Charles W; Steigleman, Walter A; Saucedo-Sanchez, Erika; Tuli, Sonal S

2013-04-01

In this study, the case of a patient who presented with reactivation of herpes zoster (HZ) keratitis and worsening of neurotrophic keratopathy, keratouveitis, and keratoconjunctivitis sicca after vaccination with live attenuated HZ vaccine (Zostavax) is described. This is a retrospective case review. A 63-year-old man, with a history of HZ keratouveitis and neurotrophic keratopathy that had been quiescent for 3.5 years off medication, presented with keratouveitis 2 weeks after Zostavax administration. Oral acyclovir and topical prednisolone acetate and cyclopentolate were started, with subsequent improvement in inflammation and visual acuity. However, the patient was unable to be tapered completely off the steroids. HZ keratouveitis is the result of cell-mediated immunity (CMI) directed toward viral antigens within the eye. The live attenuated HZ vaccine, Zostavax, boosts the recipient's CMI to prevent reactivation of HZ. However, patients with a history of HZ keratitis may have persistent viral antigens in their corneas and can develop recurrence of keratouveitis because of the vaccine-induced increase in CMI. Vaccination should be undertaken with caution in patients with a history of HZ ophthalmicus.

Helicase-primase inhibitor amenamevir for herpesvirus infection: Towards practical application for treating herpes zoster.

PubMed

Shiraki, K

2017-11-01

Valacyclovir and famciclovir enabled successful systemic therapy for treating herpes simplex virus (HSV) and varicella zoster virus (VZV) infection by their phosphorylation with viral thymidine kinase. Helicase-primase inhibitors (HPIs) inhibit the progression of the replication fork, an initial step in DNA synthesis to separate the double strand into two single strands. The HPIs amenamevir and pritelivir have a novel mechanism of action, once-daily administration with nonrenal excretory characteristics, and clinical efficacy for genital herpes. Amenamevir exhibits anti-VZV and anti-HSV activity while pritelivir only has anti-HSV activity. A clinical trial of amenamevir for herpes zoster has been completed, and amenamevir has been licensed and successfully used in 20,000 patients with herpes zoster so far in Japan. We have characterized the features of the antiviral action of amenamevir and, unlike acyclovir, the drug's antiviral activity is not influenced by the viral replication cycle. Amenamevir is opening a new era of antiherpes therapy. Copyright 2017 Clarivate Analytics.

Challenges in designing a Taqman-based multiplex assay for the simultaneous detection of Herpes simplex virus types 1 and 2 and Varicella-zoster virus.

PubMed

Weidmann, Manfred; Armbruster, Katrin; Hufert, Frank T

2008-08-01

To optimise molecular detection of herpesviruses an internally controlled multiplex Taqman-PCR for the detection of Herpes simplex virus 1 (HSV1), Herpes simplex virus 2 (HSV2) and Varicella-zoster virus (VZV) was developed. The selection of the dye combination working on the ABI 7700 cycler for this multiplex PCR revealed crosstalk phenomena between several combinations of reference dyes and reporter dyes. A final dye combination with CY5 as reference dye and FAM/JOE/TXR as reporter dyes was selected. The influence of the concentration of the internal positive control (IPC) concentration on the quantitative results of HSV1, HSV2 and VZV positive patient samples was analysed. The results indicate that high IPC concentrations are detrimental for the sensitivity of the multiplex assay and that the presence of the IPC molecule narrows the dynamic range of the duplex PCRs between any of the virus PCRs and the IPC-PCR. The optimised multiplex assay detecting HSV1, HSV2 and VZV using 10(3) IPC molecules showed a performance and sensitivity comparable to that of the individual assays.

Development and clinical validation of a multiplex real-time PCR assay for herpes simplex and varicella zoster virus.

PubMed

Tan, Thean Yen; Zou, Hao; Ong, Danny Chee Tiong; Ker, Khor Jia; Chio, Martin Tze Wei; Teo, Rachael Yu Lin; Koh, Mark Jean Aan

2013-12-01

Herpes simplex virus (HSV) and varicella zoster virus (VZV) are related members of the Herpesviridae family and are well-documented human pathogens causing a spectrum of diseases, from mucocutaneous disease to infections of the central nervous system. This study was carried out to evaluate and validate the performance of a multiplex real-time polymerase chain reaction (PCR) assay in detecting and differentiating HSV1, HSV2, and VZV from clinical samples. Consensus PCR primers for HSV were designed from the UL30 component of the DNA polymerase gene of HSV, with 2 separate hydrolysis probes designed to differentiate HSV1 and HSV2. Separate primers and a probe were also designed against the DNA polymerase gene of VZV. A total of 104 clinical samples were available for testing by real-time PCR, conventional PCR, and viral culture. The sensitivity and specificity of the real-time assay was calculated by comparing the multiplex PCR result with that of a combined standard of virus culture and conventional PCR. The sensitivity of the real-time assay was 100%, with specificity ranging from 98% to 100% depending on the target gene. Both PCR methods detected more positive samples for HSV or VZV, compared with conventional virus culture. This multiplex PCR assay provides accurate and rapid diagnostic capabilities for the diagnosis and differentiation of HSV1, HSV2, and VZV infections, with the presence of an internal control to monitor for inhibition of the PCR reaction.

Varicella infection modeling.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jones, Katherine A.; Finley, Patrick D.; Moore, Thomas W.

2013-09-01

Infectious diseases can spread rapidly through healthcare facilities, resulting in widespread illness among vulnerable patients. Computational models of disease spread are useful for evaluating mitigation strategies under different scenarios. This report describes two infectious disease models built for the US Department of Veteran Affairs (VA) motivated by a Varicella outbreak in a VA facility. The first model simulates disease spread within a notional contact network representing staff and patients. Several interventions, along with initial infection counts and intervention delay, were evaluated for effectiveness at preventing disease spread. The second model adds staff categories, location, scheduling, and variable contact rates tomore » improve resolution. This model achieved more accurate infection counts and enabled a more rigorous evaluation of comparative effectiveness of interventions.« less

Progression of varicella-zoster virus necrotizing retinopathy in an HIV-negative patient with transient immune deviation.

PubMed

Lim, Wee-Kiak; Chee, Soon-Phaik; Nussenblatt, Robert Burton

2005-06-01

To report a case of unilateral varicella-zoster virus (VZV) necrotizing retinopathy that progressed from outer retinitis with features of progressive outer retinal necrosis (PORN) to typical acute retinal necrosis (ARN) in an HIV-negative patient with a transient decrease in CD4 lymphocyte counts and CD4/CD8 ratio. Case report. A 41-year-old Chinese man presenting with blurred vision in the right eye was diagnosed with herpetic necrotizing retinitis without vitritis. Fundus examination revealed retinal arteritis and extensive deep whitish retinal lesions in the mid-periphery with minimal vitritis. Aqueous humor and vitreous PCR were positive for VZV. His CD4 count on presentation was depressed (239 cells/ul) and the CD4/CD8 ratio was low (0.8). The referring ophthalmologist had treated him with prednisolone 60 mg/day. At our institution, when intravenous acyclovir was started and the steroid therapy discontinued, he developed severe vitritis and the deep retinal lesions progressed to full-thickness retinitis typical of ARN. Repeat CD4 count was 512 cells/ul at day 14. In total, he was treated with 14 days of i.v. acyclovir (12 mg/kg 8-hourly) followed by oral valaciclovir 500 mg three times a day for 3 months. Prednisolone 30 mg once daily was restarted and tapered over 3 months. Despite prophylactic argon retinal photocoagulation to the edge of the retinitis, the patient developed a total retinal detachment at 3 months. VZV retinal infection in an HIV-negative patient with transient immune deviation can manifest initially as outer retinitis with features similar to PORN and progress to typical ARN when CD4 counts return to normal.

Vaccines for preventing herpes zoster in older adults.

PubMed

Gagliardi, Anna M Z; Gomes Silva, Brenda Nazaré; Torloni, Maria R; Soares, Bernardo G O

2012-10-17

Herpes zoster or, as it is commonly called, 'shingles' is a neurocutaneous disease characterised by the reactivation of varicella zoster virus (VZV), the virus that causes chickenpox, which is latent in the dorsal spinal ganglia when immunity to VZV declines. It is an extremely painful condition which can often last for many weeks or months, impairing the patient's quality of life. The natural aging process is associated with a reduction of cellular immunity which predisposes to herpes zoster. Vaccination with an attenuated form of VZV activates specific T cell production, therefore avoiding viral reactivation. A herpes zoster vaccine with an active virus has been approved for clinical use among older adults by the Food and Drug Administration and has been tested in large populations. To evaluate the effectiveness and safety of vaccination for preventing herpes zoster in older adults. We searched the following sources for relevant studies: CENTRAL 2012, Issue 7, MEDLINE (1948 to July week 1, 2012), EMBASE (2010 to July 2012), LILACS (1982 to July 2012) and CINAHL (1981 to July 2012). We also reviewed reference lists of identified trials and reviews for additional studies. Randomised controlled trials (RCTs) or quasi-RCTs comparing zoster vaccine with placebo or no vaccine, to prevent herpes zoster in older adults (mean age > 60 years). Two review authors independently collected and analysed data using a data extraction form. They also carried out an assessment of risk of bias. We identified eight RCTs with a total of 52,269 participants. Three studies were classified at low risk of bias. The main outcomes on effectiveness and safety were extracted from one clinical trial with a low risk of bias. Four studies compared zoster vaccine versus placebo; one study compared high-potency zoster vaccine versus low-potency zoster vaccine; one study compared refrigerated zoster vaccine versus frozen zoster vaccine; one study compared live zoster vaccine versus inactivated

Simultaneous detection of and differentiation between herpes simplex and varicella-zoster viruses with two fluorescent probes in the same test system.

PubMed

Brumback, B G; Farthing, P G; Castellino, S N

1993-12-01

Specimens from skin lesions were examined simultaneously for herpes simplex virus (HSV) and varicella-zoster virus (VZV) by direct specimen testing and shell vial culture in single-test systems. For direct testing, cells in a single specimen well were stained with a combination direct-indirect immunofluorescence stain by using two fluorescent tags. A total of 203 fresh specimens were tested in parallel. Of these, 100 specimens contained too few cells for the direct VZV comparison and 91 contained too few cells for the HSV comparison. After these specimens were eliminated, the sensitivities and specificities, respectively, of the dual direct test were 86.1 and 97.3% for HSV compared with single culture and 92.2 and 100% for VZV compared with single direct testing. Shell vial monolayers in the combined cultures were stained for both viruses by the same method. A total of 305 fresh specimens were cultured in parallel by dual- and single-culture methods. The sensitivities and specificities, respectively, of the combined culture compared with separate cultures were 100 and 98.4% for HSV and 87.9 and 99.2% for VZV. The combined methods gave a performance comparable to those of single tests, required less specimen volume, and were less costly to perform.

The herpes zoster subunit vaccine.

PubMed

Cunningham, Anthony L

2016-01-01

Herpes zoster (HZ) causes severe pain and rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN). HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age related or other causes of decreased T cell immunity. A concentrated live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 5-8 years. The new HZ subunit (HZ/su or Shingrix) vaccine combines a key surface VZV glycoprotein (E) with T cell boosting adjuvant (AS01B). It is highly efficacious in protection (97%) against HZ in immunocompetent subjects, with no decline in advancing age and protection maintained for >3 years. Phase I-II trials showed safety and similar immunogenicity in severely immunocompromised patients. Local injection site pain and swelling can be severe in a minority (9.5%) but is transient (2 days). The HZ/su vaccine appears very promising in immunocompetent patients in the ZoE-50 controlled trial. The unblinding of the current ZoE-50 trial and publication of results from the accompanying ZoE-70 trial will reveal more about its mechanism of action and its efficacy against PHN, particularly in subjects >70 years. Phase III trial results in immunocompromised patients are eagerly awaited.

A deterministic model for highly contagious diseases: The case of varicella

NASA Astrophysics Data System (ADS)

Acedo, L.; Moraño, J.-A.; Santonja, F.-J.; Villanueva, R.-J.

2016-05-01

The classic nonlinear Kermack-McKendrick model based upon a system of differential equations has been widely applied to model the rise and fall of global pandemic and also seasonal epidemic by introducing a forced harmonic infectivity which would change throughout the year. These methods work well in their respective domains of applicability, and for certain diseases, but they fail when both seasonality and high infectivity are combined. In this paper we consider a Susceptible-Infected-Recovered, or SIR, model with two latent states to model the propagation and evolutionary history of varicella in humans. We show that infectivity can be calculated from real data and we find a nonstandard seasonal variation that cannot be fitted with a single harmonic. Moreover, we show that infectivity for the present strains of the virus has raised following a sigmoid function in a period of several centuries. This could allow the design of vaccination strategies and the study of the epidemiology of varicella and herpes zoster.

Vaccines for post-exposure prophylaxis against varicella (chickenpox) in children and adults.

PubMed

Macartney, Kristine; Heywood, Anita; McIntyre, Peter

2014-06-23

The prevention of varicella (chickenpox) using live attenuated varicella vaccines has been demonstrated both in randomised controlled trials (RCTs) and in population-based immunisation programmes in countries such as the United States and Australia. Many countries do not routinely immunise children against varicella and exposures continue to occur. Although the disease is often mild, complications such as secondary bacterial infection, pneumonitis and encephalitis occur in about 1% of cases, usually leading to hospitalisation. The use of varicella vaccine in persons who have recently been exposed to the varicella zoster virus has been studied as a form of post-exposure prophylaxis (PEP). To assess the efficacy and safety of vaccines for use as PEP for the prevention of varicella in children and adults. We searched CENTRAL (2014, Issue 1), MEDLINE (1966 to March week 1, 2014), EMBASE (January 1990 to March 2014) and LILACS (1982 to March 2014). We searched for unpublished trials registered on the clinicaltrials.gov and WHO ICTRP websites. RCTs and quasi-RCTs of varicella vaccine for PEP compared with placebo or no intervention. The outcome measures were efficacy in prevention of clinical cases and/or laboratory-confirmed clinical cases and adverse events following vaccination. Two review authors independently extracted and analysed data using Review Manager software. We identified three trials involving 110 healthy children who were siblings of household contacts. The included trials varied in study quality, vaccine used, length of follow-up and outcomes measured and, as such, were not suitable for meta-analysis. We identified high or unclear risk of bias in two of the three included studies. Overall, 13 out of 56 vaccine recipients (23%) developed varicella compared with 42 out of 54 placebo (or no vaccine) recipients (78%). Of the vaccine recipients who developed varicella, the majority only had mild disease (with fewer than 50 skin lesions). In the three trials

Zoster duplex: a clinical report and etiologic analysis.

PubMed

Zhang, Feng; Zhou, Jin

2015-01-01

Herpes zoster (HZ) duplex is a rare disease presentation. The mechanisms of varicella zoster virus (VZV) reactivation in multiple dermal regions are unknown. To present a HZ duplex case occurring in an immunocompetent woman and to analyze the possible underlying causes of HZ duplex. We present a HZ duplex case in an immunocompetent woman and analyzed the possible contributing factors in 36 HZ duplex cases. Continuously distributed variables were categorized by numbers and percentages. In our study, 24 cases (66.7%) were from Asia, 16 cases (44.4%) were in individuals ≥ 50 years of age, and 17 cases (47.2%) occurred in immunocompromised patients. Of the 36 cases, 23 involved women (63.9%) and 13 involved men. Eighteen patients suffering from HZ duplex, 13 of which were women (72.2%), did not suffer from any chronic systemic disease or have a long history of taking drugs. HZ duplex is a rare event that can occur in both immunocompetent and immunosuppressed individuals. HZ duplex might be associated with the Asia region, advanced age, immunosuppression, and being female.

Post-licensure safety surveillance of zoster vaccine live (Zostavax®) in the United States, Vaccine Adverse Event Reporting System (VAERS), 2006-2015.

PubMed

Miller, Elaine R; Lewis, Paige; Shimabukuro, Tom T; Su, John; Moro, Pedro; Woo, Emily Jane; Jankosky, Christopher; Cano, Maria

2018-03-26

Herpes zoster (HZ), or shingles, is caused by reactivation of varicella-zoster virus in latently infected individuals. Live-attenuated HZ vaccine (zoster vaccine live, ZVL) is approved in the United States for persons aged ≥50 years and recommended by the CDC for persons ≥60 years. We analyzed U.S. reports of adverse events (AEs) following ZVL submitted to the Vaccine Adverse Event Reporting System (VAERS), a spontaneous reporting system to monitor vaccine safety, for persons vaccinated May 1, 2006, through January 31, 2015. We conducted descriptive analysis, clinical reviews of reports with selected pre-specified conditions, and empirical Bayesian data mining. VAERS received 23,092 reports following ZVL, of which 22,120 (96%) were classified as non-serious. Of reports where age was documented (n = 18,817), 83% were in persons aged ≥60 years. Reporting rates of AEs were 106 and 4.4 per 100,000 ZVL doses distributed for all reports and serious reports, respectively. When ZVL was administered alone among persons aged ≥50 years, injection site erythema (27%), HZ (17%), injection site swelling (17%), and rash (14%) were the most commonly reported symptoms among non-serious reports; HZ (29%), pain (18%), and rash (16%) were the most commonly reported symptoms among serious reports. Six reports included laboratory evidence of vaccine-strain varicella-zoster virus (Oka/Merck strain) infection; AEs included HZ, HZ- or varicella-like illness, and local reaction with vesicles. In our review of reports of death with sufficient information to determine cause (n = 46, median age 75 years), the most common causes were heart disease (n = 28), sepsis (n = 4), and stroke (n = 3). Empirical Bayesian data mining did not detect new or unexpected safety signals. Findings from our safety review of ZVL are consistent with those from pre-licensure clinical trials and other post-licensure assessments. Transient injection-site reactions, HZ, and rashes were most frequently

Compounds that target host cell proteins prevent varicella-zoster virus replication in culture, ex vivo, and in SCID-Hu mice.

PubMed

Rowe, Jenny; Greenblatt, Rebecca J; Liu, Dongmei; Moffat, Jennifer F

2010-06-01

Varicella-zoster virus (VZV) replicates in quiescent T cells, neurons, and skin cells. In cultured fibroblasts (HFFs), VZV induces host cyclin expression and cyclin-dependent kinase (CDK) activity without causing cell cycle progression. CDK1/cyclin B1 phosphorylates the major viral transactivator, and the CDK inhibitor roscovitine prevents VZV mRNA transcription. We investigated the antiviral effects of additional compounds that target CDKs or other cell cycle enzymes in culture, ex vivo, and in vivo. Cytotoxicity and cell growth arrest doses were determined by Neutral Red assay. Antiviral effects were evaluated in HFFs by plaque assay, genome copy number, and bioluminescence. Positive controls were acyclovir (400 microM) and phosphonoacetic acid (PAA, 1 mM). Test compounds were roscovitine, aloisine A, and purvalanol A (CDK inhibitors), aphidicolin (inhibits human and herpesvirus DNA polymerase), l-mimosine (indirectly inhibits human DNA polymerase), and DRB (inhibits casein kinase 2). All had antiviral effects below the concentrations required for cell growth arrest. Compounds were tested in skin organ culture at EC(99) doses; all prevented VZV replication in skin, except for aloisine A and purvalanol A. In SCID mice with skin xenografts, roscovitine (0.7 mg/kg/day) was as effective as PAA (36 mg/kg/day). The screening systems described here are useful models for evaluating novel antiviral drugs for VZV. Copyright 2010 Elsevier B.V. All rights reserved.

The prevention and management of herpes zoster.

PubMed

Cunningham, Anthony L; Breuer, Judith; Dwyer, Dominic E; Gronow, David W; Helme, Robert D; Litt, John C; Levin, Myron J; Macintyre, C Raina

2008-02-04

The burden of illness from herpes zoster (HZ) and postherpetic neuralgia (PHN) in the Australian community is high. The incidence and severity of HZ and PHN increase with age in association with a progressive decline in cell-mediated immunity to varicella-zoster virus (VZV). Antiviral medications (valaciclovir, famciclovir, aciclovir) have been shown to be effective in reducing much but not all of the morbidity associated with HZ and PHN, but are consistently underprescribed in Australia. Zoster-associated pain should be treated early and aggressively, as it is more difficult to treat once established. Clinicians should be proactive in their follow-up of individuals at high risk of developing PHN, and refer patients to a specialist pain clinic earlier, rather than later. A live, attenuated VZV vaccine (Oka/Merck strain, Zostavax [Merck Sharp & Dohme]) has proven to be efficacious in reducing the incidence of and morbidity associated with HZ and PHN in older adults. The vaccine's efficacy has been shown to persist for at least 4 years, but is likely to last a lot longer. Ongoing surveillance will determine the duration of protection and whether a booster dose is required. Clinicians should consider recommending the vaccine, which can be safely administered at the same time as the inactivated influenza vaccine, to all immunocompetent patients aged 60 years or older. Clinicians should refer to the Australian immunisation handbook for advice on the use of the live vaccine in immunosuppressed individuals.

Recombinant glycoprotein E produced in mammalian cells in large-scale as an antigen for varicella-zoster-virus serology.

PubMed

Thomsson, Elisabeth; Persson, Linn; Grahn, Anna; Snäll, Johanna; Ekblad, Maria; Brunhage, Eva; Svensson, Frida; Jern, Christina; Hansson, Gunnar C; Bäckström, Malin; Bergström, Tomas

2011-07-01

A recombinant glycoprotein E (gE) from varicella-zoster virus (VZV) was generated and produced in Chinese Hamster Ovary (CHO) cells, in the development of a specific antigen for analysis of IgG antibodies to VZV. Several stable gE-secreting clones were established and one clone was adapted to growth in serum-free suspension culture. When the cells were cultured in a perfusion bioreactor, gE was secreted into the medium, from where it could be easily purified. The recombinant gE was then evaluated as a serological antigen in ELISA. When compared to a conventional whole virus antigen, the VZV gE showed similar results in ELISA-based seroprevalence studies of 854 samples derived from blood donors, students, ischemic stroke patients and their controls, including samples with border-line results in previous analyses. Eight samples (0.9%) were discordant, all being IgG-negative by the VZV gE ELISA and positive by the whole virus ELISA. The sensitivity and specificity of the VZV gE ELISA were 99.9% and 100%, respectively, compared to 100% and 88.9% for the VZV whole virus ELISA. The elderly subjects showed similar reactivities to both antigens, while VZV gE gave lower signals in the younger cohorts, suggesting that antibodies to gE may increase with age. It was concluded that the recombinant VZV gE from CHO cells was suitable as a serological antigen for the detection of IgG antibodies specific for VZV. Copyright © 2011 Elsevier B.V. All rights reserved.

The Shozu Herpes Zoster (SHEZ) study: rationale, design, and description of a prospective cohort study.

PubMed

Takao, Yukiko; Miyazaki, Yoshiyuki; Onishi, Fumitake; Kumihashi, Hideaki; Gomi, Yasuyuki; Ishikawa, Toyokazu; Okuno, Yoshinobu; Mori, Yasuko; Asada, Hideo; Yamanishi, Koichi; Iso, Hiroyasu

2012-01-01

The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese.

The Shozu Herpes Zoster (SHEZ) Study: Rationale, Design, and Description of a Prospective Cohort Study

PubMed Central

Takao, Yukiko; Miyazaki, Yoshiyuki; Onishi, Fumitake; Kumihashi, Hideaki; Gomi, Yasuyuki; Ishikawa, Toyokazu; Okuno, Yoshinobu; Mori, Yasuko; Asada, Hideo; Yamanishi, Koichi; Iso, Hiroyasu

2012-01-01

Background The incidence and risk factors for herpes zoster have been studied in cross-sectional and cohort studies, although most such studies have been conducted in Western countries. Evidence from Asian populations is limited, and no cohort study has been conducted in Asia. We are conducting a 3-year prospective cohort study in Shozu County in Kagawa Prefecture, Japan to determine the incidence and predictive and immunologic factors for herpes zoster among Japanese. Methods The participants are followed for 3 years, and a telephone survey is conducted every 4 weeks. The participants were assigned to 1 of 3 studies. Participants in study A gave information on past history of herpes zoster and completed health questionnaires. Study B participants additionally underwent varicella-zoster virus (VZV) skin testing, and study C participants additionally underwent blood testing. If the participants develop herpes zoster, we evaluate clinical symptoms, measure cell-mediated immunity and humoral immunity using venous blood sampling, photograph skin areas with rash, conduct virus identification testing by polymerase chain reaction (PCR) and virus isolation from crust sampling, and evaluate postherpetic pain. Results We recruited 12 522 participants aged 50 years or older in Shozu County from December 2009 through November 2010. The participation rate was 65.7% of the target population. Conclusions The present study is likely to provide valuable data on the incidence and predictive and immunologic factors for herpes zoster in a defined community-based population of Japanese. PMID:22343323

Performance of a time-resolved fluorescence immunoassay for measuring varicella-zoster virus immunoglobulin G levels in adults and comparison with commercial enzyme immunoassays and Merck glycoprotein enzyme immunoassay.

PubMed

Maple, P A C; Gray, J; Breuer, J; Kafatos, G; Parker, S; Brown, D

2006-02-01

Highly sensitive and specific, quantitative assays are needed to detect varicella-zoster virus (VZV) immunoglobulin G in human sera, particularly for determining immune status and response following vaccination. A time-resolved fluorescence immunoassay (TRFIA) has been developed, and its performance was compared to that of two commercial enzyme immunoassays (EIAs) and Merck glycoprotein EIA (gpEIA). The TRFIA had equivalent sensitivity (97.8%) and high specificity (93.5%) in relation to gpEIA. A commercial (Behring) EIA compared favorably with TRFIA in terms of sensitivity (98.4%) but had lower specificity (80.7%). Another commercial EIA (Diamedix) had high specificity (97.1%) but low sensitivity (76.4%) compared to TRFIA if equivocal test results were treated as negative for VZV antibody. A novel feature of the TRFIA was that the cutoff was generated using population mixture modeling and was expressed in mIU/ml, as the assay was calibrated using the British standard VZV antibody.

Herpes zoster ophthalmicus.

PubMed

Sanjay, Srinivasan; Huang, Philemon; Lavanya, Raghavan

2011-02-01

complete. Vasculitis within the orbital apex (orbital apex syndrome) or brainstem dysfunction is postulated to be the cause of cranial nerve palsies. A vaccine of a lyophilized preparation of the oka strain of live, attenuated varicella-zoster virus is suggested for patients who are at risk of developing HZ and has been shown to boost immunity against HZ virus in older patients.

Rapid automation of a cell-based assay using a modular approach: case study of a flow-based Varicella Zoster Virus infectivity assay.

PubMed

Joelsson, Daniel; Gates, Irina V; Pacchione, Diana; Wang, Christopher J; Bennett, Philip S; Zhang, Yuhua; McMackin, Jennifer; Frey, Tina; Brodbeck, Kristin C; Baxter, Heather; Barmat, Scott L; Benetti, Luca; Bodmer, Jean-Luc

2010-06-01

Vaccine manufacturing requires constant analytical monitoring to ensure reliable quality and a consistent safety profile of the final product. Concentration and bioactivity of active components of the vaccine are key attributes routinely evaluated throughout the manufacturing cycle and for product release and dosage. In the case of live attenuated virus vaccines, bioactivity is traditionally measured in vitro by infection of susceptible cells with the vaccine followed by quantification of virus replication, cytopathology or expression of viral markers. These assays are typically multi-day procedures that require trained technicians and constant attention. Considering the need for high volumes of testing, automation and streamlining of these assays is highly desirable. In this study, the automation and streamlining of a complex infectivity assay for Varicella Zoster Virus (VZV) containing test articles is presented. The automation procedure was completed using existing liquid handling infrastructure in a modular fashion, limiting custom-designed elements to a minimum to facilitate transposition. In addition, cellular senescence data provided an optimal population doubling range for long term, reliable assay operation at high throughput. The results presented in this study demonstrate a successful automation paradigm resulting in an eightfold increase in throughput while maintaining assay performance characteristics comparable to the original assay. Copyright 2010 Elsevier B.V. All rights reserved.

Measles, rubella, mumps, and varicella seroprevalence among health care workers in Turkey: is prevaccination screening cost-effective?

PubMed

Celikbas, Aysel; Ergonul, Onder; Aksaray, Sabahat; Tuygun, Nilden; Esener, Harika; Tanir, Gonul; Eren, Sebnem; Baykam, Nurcan; Guvener, Engin; Dokuzoguz, Basak

2006-11-01

To investigate the immune status of health care workers (HCWs) against measles, rubella, mumps, and varicella zoster (MMRV) in Turkey and to define an appropriate vaccination program among HCWs. Voluntary HCWs from a children's hospital and a general hospital were included in the study between March and May 2005. The specific IgG antibodies against MMRV viruses were screened by ELISA. Three hundred sixty-three HCWs participated in the study; 186 (51%) were physicians, 118 (33%) were nurses, 36 (10%) were housekeeping staff, and 23 (6%) were medical technicians. The proportion of HCWs who had antibodies against measles was 98.6%; rubella, 98.3%; mumps, 92.2%; and varicella, 98%. No association was found between the susceptibility to at least 1 of MMRV virus infections and gender, age, duration of work, profession, and department of work in analysis either among the whole study group, or each hospital. The positive predictive value for the history of varicella was 100%, whereas it was 92% for MMR. The cost of vaccination for varicella was significantly expensive without screening before vaccination. However, there was not much difference for MMR infections. A policy based on obtaining the history of varicella infection from the staff and then screening the ones with negative history and vaccination of only seronegative HCWs was found to be appropriate.

The health and economic burden of chickenpox and herpes zoster in Belgium.

PubMed

Bilcke, J; Ogunjimi, B; Marais, C; de Smet, F; Callens, M; Callaert, K; van Kerschaver, E; Ramet, J; van Damme, P; Beutels, P

2012-11-01

Varicella-zoster virus causes chickenpox (CP) and after reactivation herpes zoster (HZ). Vaccines are available against both diseases warranting an assessment of the pre-vaccination burden of disease. We collected data from relevant Belgian databases and performed five surveys of CP and HZ patients. The rates at which a general practitioner is visited at least once for CP and HZ are 346 and 378/100 000 person-years, respectively. The average CP and HZ hospitalization rates are 5·3 and 14·2/100 000 person-years respectively. The direct medical cost for HZ is about twice as large as the direct medical cost for CP. The quality-adjusted life years lost for ambulatory CP patients consulting a physician is more than double that of those not consulting a physician (0·010 vs. 0·004). In conclusion, both diseases cause a substantial burden in Belgium.

Structural Organization and Strain Variation in the Genome of Varicella Zoster Virus

DTIC Science & Technology

1984-10-23

Zoster 6 Growth of VZV in tissue culture 9 Structure and proteins of VZV 15 Structure of HSV DNA 20 Classification of herpesviruses based on DNA...structure 28 Strain variation in herpesvirus DNA 31 VZV DNA 33 Specific aims 36 II. MATERIALS AND METHODS 38 Cells and viruses 38 Isolation of virus...endonuclease fragments by colony hybridization 106 21. Selected methods of restriction endonuclease mapping .... 109 22. Identification of

Herpes Zoster and Postherpetic Neuralgia: Practical Consideration for Prevention and Treatment

PubMed Central

2015-01-01

Herpes zoster (HZ) is a transient disease caused by the reactivation of latent varicella zoster virus (VZV) in spinal or cranial sensory ganglia. It is characterized by a painful rash in the affected dermatome. Postherpetic neuralgia (PHN) is the most troublesome side effect associated with HZ. However, PHN is often resistant to current analgesic treatments such as antidepressants, anticonvulsants, opioids, and topical agents including lidocaine patches and capsaicin cream and can persist for several years. The risk factors for reactivation of HZ include advanced age and compromised cell-mediated immunity (CMI). Early diagnosis and treatment with antiviral agents plus intervention treatments is believed to shorten the duration and severity of acute HZ and reduce the risk of PHN. Prophylactic vaccination against VZV can be the best option to prevent or reduce the incidence of HZ and PHN. This review focuses on the pathophysiology, clinical features, and management of HZ and PHN, as well as the efficacy of the HZ vaccine. PMID:26175877

Disease burden of herpes zoster in Sweden - predominance in the elderly and in women - a register based study

PubMed Central

2013-01-01

Background The herpes zoster burden of disease in Sweden is not well investigated. There is no Swedish immunization program to prevent varicella zoster virus infections. A vaccine against herpes zoster and its complications is now available. The aim of this study was to estimate the herpes zoster burden of disease and to establish a pre-vaccination baseline of the minimum incidence of herpes zoster. Methods Data were collected from the Swedish National Health Data Registers including the Patient Register, the Pharmacy Register, and the Cause of Death Register. The herpes zoster burden of disease in Sweden was estimated by analyzing the overall, and age and gender differences in the antiviral prescriptions, hospitalizations and complications during 2006-2010 and mortality during 2006-2009. Results Annually, 270 per 100,000 persons received antiviral treatment for herpes zoster, and the prescription rate increased with age. It was approximately 50% higher in females than in males in the age 50+ population (rate ratio 1.39; 95% CI, 1.22 to 1.58). The overall hospitalization rate for herpes zoster was 6.9/100,000 with an approximately three-fold increase for patients over 80 years of age compared to the age 70-79 group. A gender difference in hospitalization rates was observed: 8.1/100,000 in females and 5.6/100,000 in males. Herpes zoster, with a registered complication, was found in about one third of the hospitalized patients and the most common complications involved the peripheral and central nervous systems. Death due to herpes zoster was a rare event. Conclusions The results of this study demonstrate the significant burden of herpes zoster disease in the pre-zoster vaccination era. A strong correlation with age in the herpes zoster- related incidence, hospitalization, complications, and mortality rates was found. In addition, the study provides further evidence of the female predominance in herpes zoster disease. PMID:24330510

Varicella Zoster Virus Induces Nuclear Translocation of the Neurokinin-1 Receptor, Promoting Lamellipodia Formation and Viral Spread in Spinal Astrocytes.

PubMed

Bubak, Andrew N; Como, Christina N; Blackmon, Anna M; Frietze, Seth; Mescher, Teresa; Jones, Dallas; Cohrs, Randall J; Paucek, Petr; Baird, Nicholas L; Nagel, Maria A

2018-05-19

Varicella zoster virus (VZV) can present as a myelopathy with spinal astrocyte infection. Recent studies support a role for the neurokinin-1 receptor (NK-1R) in virus infections, as well as for cytoskeletal alterations that may promote viral spread. Thus, we examined the role of NK-1R in VZV-infected primary human spinal astrocytes (HA-sps) to shed light on the pathogenesis of VZV myelopathy. Mock- and VZV-infected HA-sps were examined for substance P (subP) production, NK-1R localization, morphological changes and viral spread in the presence or absence of NK-1R antagonists, aprepitant and rolapitant. VZV infection of HA-sps induced nuclear localization of full-length and truncated NK-1R in the absence of the endogenous ligand, subP, and was associated with extensive lamellipodia formation and viral spread that was inhibited by NK-1R antagonists. We have identified a novel, subP-independent, proviral function of nuclear NK-1R associated with lamellipodia formation and viral spread that is distinct from subP-induced NK-1R cell membrane/cytoplasmic localization without lamellipodia formation. These results suggest that binding of a putative viral ligand to NK-1R produces a dramatically different NK-1R downstream effect than binding of subP. Finally, NK-1R antagonists aprepitant and rolapitant provide promising alternatives to nucleoside analogs in treating VZV infections, including myelopathy.

Clinical features of viral meningitis in adults: significant differences in cerebrospinal fluid findings among herpes simplex virus, varicella zoster virus, and enterovirus infections.

PubMed

Ihekwaba, Ugo K; Kudesia, Goura; McKendrick, Michael W

2008-09-15

In this retrospective study, our objective was to review the epidemiology of viral meningitis and to compare clinical features associated with enterovirus, herpes simplex virus (HSV), and varicella zoster virus (VZV) infections in immunocompetent adults. Data on cerebrospinal fluid (CSF) samples submitted to the Trust Virology Laboratory (Sheffield, UK) from April 2004 through April 2007 were reviewed. Notes on immunocompetent adults who were polymerase chain reaction (PCR) positive for enterovirus, HSV type 2, or VZV and who had presented to local clinical departments were scrutinized (4 patients were positive for HSV type 1 and did not meet the inclusion criteria). A total of 2045 samples were analyzed for viral pathogens during the 3-year period. Of the 109 PCR-positive samples, 38 (35%) were from immunocompetent adults, of whom 22 were infected with enterovirus, 8 were infected with HSV type 2, and 8 were infected with VZV. The median ages were 32 years (range, 16-39 years), 39 years (range, 22-53 years), and 47.5 years (range, 26-80 years), respectively. Rash occurred after the meningitis symptoms in 5 patients infected with VZV (median time from meningitis symptoms to rash, 6 days). Protein levels were significantly higher in CSF samples from patients infected with HSV type 2 (median, 1205 mg/L) and in samples from those infected with VZV (median, 974 mg/L) than in samples from those infected with enterovirus (median, 640 mg/L; P = .001 and P = .01, respectively). White blood cell counts were significantly higher in CSF samples from patients infected with HSV type 2 (median, 240 x 10(6) cells/L) than in samples from those infected with enterovirus (median, 51 x 10(6) cells/L; P = .01). Enterovirus infection was the most common cause of viral meningitis in immunocompetent adults in this study. White blood cell counts and protein levels were significantly higher in CSF samples from patients infected with HSV type 2 than in samples from patients with enterovirus

Development of a multiplex real-time PCR for the simultaneous detection of herpes simplex and varicella zoster viruses in cerebrospinal fluid and lesion swab specimens.

PubMed

Wong, Anita A; Pabbaraju, Kanti; Wong, Sallene; Tellier, Raymond

2016-03-01

Herpes simplex viruses (HSV) and varicella zoster virus (VZV) can have very similar and wide-ranging clinical presentations. Rapid identification is necessary for timely antiviral therapy, especially with infections involving the central nervous system, neonates, and immunocompromised individuals. Detection of HSV-1, HSV-2 and VZV was combined into one real-time PCR reaction utilizing hydrolysis probes. The assay was validated on the LightCycler(®) (Roche) and Applied Biosystems 7500 Real-Time PCR System (Thermo Fisher Scientific Inc.) to detect alphaherpesviruses in cerebral spinal fluid (CSF) and lesion swab specimens, respectively. Validation data on blood and tissue samples are also presented. The multiplex assay showed excellent sensitivity, specificity and reproducibility when compared to two singleplex real-time PCR assays for CSF samples and direct fluorescent antigen/culture for lesion swab samples. Implementation of the multiplex assay has facilitated improved sensitivity and accuracy as well as reduced turn-around-times and costs. The results from a large data set of 16,622 prospective samples tested between August 16, 2012 to February 1, 2014 at the Provincial Laboratory for Public Health (Alberta, Canada) are presented here. Copyright © 2015 Elsevier B.V. All rights reserved.

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process

PubMed Central

Marshall, Gary S.; Senders, Shelly D.; Shepard, Julie; Twiggs, Jerry D.; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E.; Helmond, Frans A.

2016-01-01

ABSTRACT Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRVAMP) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRVAMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRVAMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRVAMP. Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRVAMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases. PMID:27149048

Seasonal variation and trend of chicken pox in the southern region of Saudi Arabia (2007-2012).

PubMed

Saleh, Noha; Al Moghazy, Bassem

2014-12-01

Chicken pox is a contagious disease caused by varicella zoster virus. Children are most susceptible to infection. In 1998, the WHO recommended that routine childhood varicella vaccination be considered in countries where the disease is a relatively important public health concern. There are few data on the trends of chicken pox. We aimed to evaluate the trend of chicken pox in Saudi Arabia (KSA) during the period 2007-2012. Data were collected by retrospective review of the existing anonymous surveillance records and book registries of chicken pox cases at the preventive medicine department of Armed Forces Hospital of the Southern Region of Saudi Arabia from 2007 to 2012. The collected data included the number, age, and sex of registered cases. A seasonal pattern was clearly demonstrated, with peak in March and April. There was also a decreasing trend from 2007 to 2012. Most cases occurred in the age group 4-15 years. The number of infected male patients was a little higher compared with female patients. These results indicate success in controlling the disease in the southern region of Saudi Arabia, which may be attributed to the implementation of public health interventions targeted at reducing infectious diseases (such as the introduction of varicella zoster vaccine in 2008). We recommend that a future study be conducted on the severity of chicken pox infection in adults (hospitalization, complications, and death) and a national survey among adults for the seroprevalence of markers of infection with varicella zoster.

Pulsed Radiofrequency to the Dorsal Root Ganglion in Acute Herpes Zoster and Postherpetic Neuralgia.

PubMed

Kim, Koohyun; Jo, Daehyun; Kim, EungDon

2017-03-01

Latent varicella zoster virus reactivates mainly in sensory ganglia such as the dorsal root ganglion (DRG) or trigeminal ganglion. The DRG contains many receptor channels and is an important region for pain signal transduction. Sustained abnormal electrical activity to the spinal cord via the DRG in acute herpes zoster can result in neuropathic conditions such as postherpetic neuralgia (PHN). Although the efficacy of pulsed radiofrequency (PRF) application to the DRG in various pain conditions has been previously reported, the application of PRF to the DRG in patients with herpes zoster has not yet been studied. The aim of the present study was to compare the clinical effects of PRF to the DRG in patients with herpes zoster to those of PRF to the DRG in patients with PHN. Retrospective comparative study. University hospital pain center in Korea. The medical records of 58 patients who underwent PRF to the DRG due to zoster related pain (herpes zoster or PHN) were retrospectively analyzed. Patients were divided into 2 groups according to the timing of PRF after zoster onset: an early PRF group (within 90 days) and a PHN PRF group (more than 90 days). The efficacy of PRF was assessed by a numeric rating scale (NRS) and by recording patient medication doses before PRF and at one week, 4 weeks, 8 weeks, and 12 weeks after PRF. Pain intensity was decreased after PRF in all participants. However, the degree of pain reduction was significantly higher in the early PRF group. Moreover, more patients discontinued their medication in the early PRF group, and the PRF success rate was also higher in the early PRF group. The relatively small sample size from a single center, short duration of review of medical records, and the retrospective nature of the study. PRF to the DRG is a useful treatment for treatment-resistant cases of herpes zoster and PHN. Particularly in herpes zoster patients with intractable pain, application of PRF to the DRG should be considered for pain control

Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*.

PubMed

L'Huillier, A G; Ferry, T; Courvoisier, D S; Aebi, C; Cheseaux, J-J; Kind, C; Rudin, C; Nadal, D; Hirschel, B; Sottas, C; Siegrist, C-A; Posfay-Barbe, K M

2012-01-01

HIV-infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV-infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV-infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response. In a prospective, cross-sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme-linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV-infected children and 78 HIV-infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age-matched healthy children. We also tested antibody avidity in HIV-infected and healthy children. Median anti-VZV immunoglobulin G (IgG) levels were lower in HIV-infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36-72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV-infected children. Anti-VZV antibodies did not decline more rapidly in HIV-infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV-infected children. Thus, antibody levels were lower in HIV-infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV-infected than healthy children (P<0.001). A direct correlation between anti-VZV IgG level and avidity was present in HIV-infected children (P=0.001), but not in healthy children. Failure to maintain anti-VZV IgG levels in HIV-infected children results from failure to reactivate memory responses. Further studies are required to investigate long-term protection and the potential benefits of immunization. © 2011 British HIV Association.

Transcriptional mapping of the varicella-zoster virus regulatory genes encoding open reading frames 4 and 63.

PubMed Central

Kinchington, P R; Vergnes, J P; Defechereux, P; Piette, J; Turse, S E

1994-01-01

Four of the 68 varicella-zoster virus (VZV) unique open reading frames (ORFs), i.e., ORFs 4, 61, 62, and 63, encode proteins that influence viral transcription and are considered to be positional homologs of herpes simplex virus type 1 (HSV-1) immediate-early (IE) proteins. In order to identify the elements that regulate transcription of VZV ORFs 4 and 63, the encoded mRNAs were mapped in detail. For ORF 4, a major 1.8-kb and a minor 3.0-kb polyadenylated [poly(A)+] RNA were identified, whereas ORF 63-specific probes recognized 1.3- and 1.9-kb poly(A)+ RNAs. Probes specific for sequences adjacent to the ORFs and mapping of the RNA 3' ends indicated that the ORF 4 RNAs were 3' coterminal, whereas the RNAs for ORF 63 represented two different termination sites. S1 nuclease mapping and primer extension analyses indicated a single transcription initiation site for ORF 4 at 38 bp upstream of the ORF start codon. For ORF 63, multiple transcriptional start sites at 87 to 95, 151 to 153, and (tentatively) 238 to 243 bp upstream of the ORF start codon were identified. TATA box motifs at good positional locations were found upstream of all mapped transcription initiation sites. However, no sequences resembling the TAATGARAT motif, which confers IE regulation upon HSV-1 IE genes, were found. The finding of the absence of this motif was supported through analyses of the regulatory sequences of ORFs 4 and 63 in transient transfection assays alongside those of ORFs 61 and 62. Sequences representing the promoters for ORFs 4, 61, and 63 were all stimulated by VZV infection but failed to be stimulated by coexpression with the HSV-1 transactivator Vmw65. In contrast, the promoter for ORF 62, which contains TAATGARAT motifs, was activated by VZV infection and coexpression with Vmw65. These results extend the transcriptional knowledge for VZV and suggest that ORFs 4 and 63 contain regulatory signals different from those of the ORF 62 and HSV-1 IE genes. Images PMID:8189496

Recognition of similar epitopes on varicella-zoster virus gpI and gpIV by monoclonal antibodies.

PubMed Central

Vafai, A; Wroblewska, Z; Mahalingam, R; Cabirac, G; Wellish, M; Cisco, M; Gilden, D

1988-01-01

Two monoclonal antibodies, MAb43.2 and MAb79.0, prepared against varicella-zoster virus (VZV) proteins were selected to analyze VZV gpIV and gpI, respectively. MAb43.2 reacted only with cytoplasmic antigens, whereas MAb79.0 recognized both cytoplasmic and membrane antigens in VZV-infected cells. Immunoprecipitation of in vitro translation products with MAb43.2 revealed only proteins encoded by the gpIV gene, whereas MAb79.0 precipitated proteins encoded by the gpIV and gpI genes. Pulse-chase analysis followed by immunoprecipitation of VZV-infected cells indicated reactivity of MAb43.2 with three phosphorylated precursor species of gpIV and reactivity of MAb79.0 with the precursor and mature forms of gpI and gpIV. These results indicated that (i) MAb43.2 and MAb79.0 recognize different epitopes on VZV gpIV, (ii) glycosylation of gpIV ablates recognition by MAb43.2, and (iii) gpIV is phosphorylated. To map the binding site of MAb79.0 on gpI, the pGEM transcription vector, containing the coding region of the gpI gene, was linearized, and three truncated gpI DNA fragments were generated. RNA was transcribed from each truncated fragment by using SP6 RNA polymerase, translated in vitro in a rabbit reticulocyte lysate, and immunoprecipitated with MAb79.0 and human sera. The results revealed the existence of an antibody-binding site within 14 amino acid residues located between residues 109 to 123 on the predicted amino acid sequences of gpI. From the predicted amino acid sequences, 14 residues on gpI (residues 107 to 121) displayed a degree of similarity (36%) to two regions (residues 55 to 69 and 245 to 259) of gp IV. Such similarities may account for the binding of MAb79.0 to both VZV gpI and gpIV. Images PMID:2455814

Prevalence of herpes simplex types 1 and 2, varicella zoster virus, cytomegalovirus, immunoglobulin G antibodies among female university students in Syria.

PubMed

Barah, Faraj

2012-09-01

To examine the current seroepidemiology of immunoglobulin (Ig)G for herpes simplex virus types 1 and 2 (HSV 1-2), varicella zoster virus (VZV), and cytomegalovirus (CMV) among university females of childbearing age in Syria. A cross-sectional study was conducted to examine the female students of the Pharmacy College, Kalamoon University, Deratiah, Syria, where 316 sera were collected from October 2009 to November 2010, and subjected to HSV 1-2, VZV, and CMV IgG screening and titration using enzyme-linked immunosorbent assay-based techniques in the Microbiology Laboratory. A total of 164 participants were positive for HSV 1-2 IgG giving a prevalence of 52%, leaving a relatively high proportion of susceptibility among the tested group. For VZV, 91% of the participants (n=287) were positive for its specific IgG, while, regarding CMV, 74.5% (n=235) were positive, and 25.5% were negative for CMV specific IgG. Although most participants were seropositive for herpes viruses IgG, suggesting a natural virus circulation within the community, screening for protective immunity is suggested against HSV, since a relatively high proportion of tested females are still susceptible. In addition, and because of its nasty outcomes during pregnancy, IgG against CMV should also be tested. High percentage of positivity towards VZV could be explained due to introduction of the new vaccine program, and therefore, further analysis during pregnancy is not recommended.

Acute Simian Varicella Virus Infection Causes Robust and Sustained Changes in Gene Expression in the Sensory Ganglia

PubMed Central

Arnold, Nicole; Girke, Thomas; Sureshchandra, Suhas

2016-01-01

ABSTRACT Primary infection with varicella-zoster virus (VZV), a neurotropic alphaherpesvirus, results in varicella. VZV establishes latency in the sensory ganglia and can reactivate later in life to cause herpes zoster. The relationship between VZV and its host during acute infection in the sensory ganglia is not well understood due to limited access to clinical specimens. Intrabronchial inoculation of rhesus macaques with simian varicella virus (SVV) recapitulates the hallmarks of VZV infection in humans. We leveraged this animal model to characterize the host-pathogen interactions in the ganglia during both acute and latent infection by measuring both viral and host transcriptomes on days postinfection (dpi) 3, 7, 10, 14, and 100. SVV DNA and transcripts were detected in sensory ganglia 3 dpi, before the appearance of rash. CD4 and CD8 T cells were also detected in the sensory ganglia 3 dpi. Moreover, lung-resident T cells isolated from the same animals 3 dpi also harbored SVV DNA and transcripts, suggesting that T cells may be responsible for trafficking SVV to the ganglia. Transcriptome sequencing (RNA-Seq) analysis showed that cessation of viral transcription 7 dpi coincides with a robust antiviral innate immune response in the ganglia. Interestingly, a significant number of genes that play a critical role in nervous system development and function remained downregulated into latency. These studies provide novel insights into host-pathogen interactions in the sensory ganglia during acute varicella and demonstrate that SVV infection results in profound and sustained changes in neuronal gene expression. IMPORTANCE Many aspects of VZV infection of sensory ganglia remain poorly understood, due to limited access to human specimens and the fact that VZV is strictly a human virus. Infection of rhesus macaques with simian varicella virus (SVV), a homolog of VZV, provides a robust model of the human disease. Using this model, we show that SVV reaches the ganglia early

Medical Surveillance Monthly Report (MSMR). Volume 8, Number 6, August 2002

DTIC Science & Technology

2002-08-01

infection with varicella-zoster virus (VZV) causes varicella (“ chickenpox ”), a common disease of children. Following varicella, VZV persists in latent...606-11. 11. Memorandum, subject: Policy for the use of varicella ( chickenpox ) vaccine. Assistant Secretary of Defense (Health Affairs), dated 22...against chickenpox . Vaccine 2002 Jun 7;20(19- 20):2500-7. 13. Edmunds WJ, Brisson M. The effect of vaccination on the epidemiology of varicella zoster

Infectious Complications during Tandem High-Dose Chemotherapy and Autologous Stem Cell Transplantation for Children with High-Risk or Recurrent Solid Tumors

PubMed Central

Kang, Ji-Man; Lee, Ji Won; Yoo, Keon Hee; Kim, Yae-Jean; Sung, Ki Woong; Koo, Hong Hoe

2016-01-01

We retrospectively analyzed infectious complications during tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT) in children and adolescents with high-risk or recurrent solid tumors. A total of 324 patients underwent their first HDCT/auto-SCT between October 2004 and September 2014, and 283 of them proceeded to their second HDCT/auto-SCT (a total of 607 HDCT/auto-SCTs). During the early transplant period of 607 HDCT/auto-SCTs (from the beginning of HDCT to day 30 post-transplant), bacteremia, urinary tract infection (UTI), respiratory virus infection, and varicella zoster virus (VZV) reactivation occurred in 7.1%, 2.3%, 13.0%, and 2.5% of HDCT/auto-SCTs, respectively. The early transplant period of the second HDCT/auto-SCT had infectious complications similar to the first HDCT/auto-SCT. During the late transplant period of HDCT/auto-SCT (from day 31 to 1 year post-transplant), bacteremia, UTI, and VZV reactivation occurred in 7.5%, 2.5%, and 3.9% of patients, respectively. Most infectious complications in the late transplant period occurred during the first 6 months post-transplant. There were no invasive fungal infections during the study period. Six patients died from infectious complications (4 from bacterial sepsis and 2 from respiratory virus infection). Our study suggests that infectious complications are similar following second and first HDCT/auto-SCT in children. PMID:27627440

Human antimicrobial peptides LL-37 and human β-defensin-2 reduce viral replication in keratinocytes infected with varicella zoster virus.

PubMed

Crack, L R; Jones, L; Malavige, G N; Patel, V; Ogg, G S

2012-07-01

There is mounting evidence that antimicrobial peptides have an important role in cutaneous defence, but the expression of these antimicrobial peptides in atopic eczema (AE) is still unclear. There are several families of antimicrobial peptides, including cathelicidins and human β-defensins. Patients with AE are more susceptible to severe cutaneous viral infections, including varicella zoster virus (VZV). To characterize the functional activity of the antimicrobial peptides LL-37 (human cathelicidin) and human β-defensin (hBD)-2 keratinocytes were infected with VZV, in a skin-infection model. Flow-cytometry analysis was used to investigate LL-37 expression in normal human keratinocytes, and quantitative PCR was used to determine viral loads in infected HaCaT keratinocytes and B cells, with and without exogenous LL-37 and hBD-2. LL-37 expression was present in keratinocytes, and both exogenous LL-37 and hBD-2 significantly reduced VZV load in infected keratinocytes and B cells. Specific antibodies blocked the antiviral action exhibited by these antimicrobial peptides. Pre-incubation of VZV with LL-37, but not hBD-2, further reduced VZV load. Both LL-37 and hBD-2 have an antiviral effect on VZV replication in the keratinocyte HaCaT cell line and in B cells, but their mechanism of action is different. Evidence of the relationship between antimicrobial peptide expression and higher susceptibility to infections in AE skin is still emerging. Developing novel antiviral therapies based on antimicrobial peptides may provide improved treatment options for patients with AE. © The Author(s). CED © 2012 British Association of Dermatologists.

Longitudinal Study on Oral Shedding of Herpes Simplex Virus 1 and Varicella-Zoster Virus in Individuals Infected with HIV

PubMed Central

van Velzen, Monique; Ouwendijk, Werner J.D.; Selke, Stacy; Pas, Suzan D.; van Loenen, Freek B.; Osterhaus, Albert D.M.E.; Wald, Anna; Verjans, Georges M.G.M.

2014-01-01

Primary herpes simplex virus 1 (HSV-1) and varicella-zoster virus (VZV) infection leads to a life-long latent infection of ganglia innervating the oral mucosa. HSV-1 and VZV reactivation is more common in immunocompromised individuals and may result in viral shedding in saliva. We determined the kinetics and quantity of oral HSV-1 and VZV shedding in HSV-1 and VZV seropositive individuals infected with HIV and to assess whether HSV-1 shedding involves reactivation of the same strain intra-individually. HSV-1 and VZV shedding was determined by real-time PCR of sequential daily oral swabs (n=715) collected for a median period of 31 days from 22 individuals infected with HIV. HSV-1 was genotyped by sequencing the viral thymidine kinase gene. Herpesvirus shedding was detected in 18 of 22 participants. Shedding of HSV-1 occurred frequently, on 14.3% of days, whereas solely VZV shedding was very rare. Two participants shed VZV. The median HSV-1 load was higher compared to VZV. HSV-1 DNA positive swabs clustered into 34 shedding episodes with a median duration of 2 days. The prevalence, duration and viral load of herpesvirus shedding did not correlate with CD4 counts and HIV load. The genotypes of the HSV-1 viruses shed were identical between and within shedding episodes of the same person, but were different between individuals. One-third of the individuals shed an HSV-1 strain potentially refractory to acyclovir therapy. Compared to HSV-1, oral VZV shedding is rare in individuals infected with HIV. Recurrent oral HSV-1 shedding is likely due to reactivation of the same latent HSV-1 strain. PMID:23780621

A double blind, randomized, active controlled study to assess the safety, tolerability and immunogenicity of measles, mumps rubella, and varicella vaccine (MMRV) manufactured using an alternative process.

PubMed

Marshall, Gary S; Senders, Shelly D; Shepard, Julie; Twiggs, Jerry D; Gardner, Julie; Hille, Darcy; Hartzel, Jonathan; Valenzuela, Rowan; Stek, Jon E; Helmond, Frans A

2016-08-02

Vaccination against measles, mumps, rubella, and varicella is recommended for all children in the US. Limitations manufacturing Oka/Merck strain varicella-zoster virus have hampered the availability of the combination vaccine (MMRV) against these 4 viruses, which drove the need to investigate an alternative manufacturing process. Healthy children 12-to-23 months of age at 71 US sites were randomized (1:1) to receive MMRV manufactured using an alternative process (MMRV AMP ) or the currently licensed MMRV. Subjects received 2 0.5 mL doses 3 months apart. Sera were collected before and 6 weeks after Dose-1. Adverse experiences (AEs) were collected for 42 d after each dose and serious AEs and events of special interest for 180 d after Dose-2. Overall, 706 subjects were randomized to MMRV AMP and 706 to MMRV and 698 and 702 received at least 1 dose of study vaccine, respectively. The risk difference in response rates and geometric mean concentrations of antibody to measles, mumps, rubella, and varicella viruses 6 weeks after Dose-1 met non-inferiority criteria for MMRV AMP versus, MMRV. Response rates met acceptability criteria for each virus, and the seroconversion rate to varicella-zoster virus was 99.5% in both groups. Vaccine-related AEs were mostly mild-to-moderate in intensity and somewhat more common after MMRV AMP . Febrile seizures occurred at similar rates in both groups during the first 42 d after each vaccine dose. MMRV AMP is non-inferior to MMRV and represents an important advancement in maintaining an adequate supply of vaccines against these diseases.

Herpes Zoster and Dementia: A Nationwide Population-Based Cohort Study.

PubMed

Chen, Vincent Chin-Hung; Wu, Shu-I; Huang, Kuo-You; Yang, Yao-Hsu; Kuo, Ting-Yu; Liang, Hsin-Yi; Huang, Kuan-Lun; Gossop, Michael

Some infectious diseases have been found to be associated with cognitive impairment and dementia. However, the relationship between herpes zoster and dementia has received little attention. This study aimed to investigate this association as well as associations of antiviral treatments for herpes zoster and incident dementia using a large national sample. Cases were identified from the Taiwan National Health Insurance Research Database with a new diagnosis of herpes zoster (ICD-9-CM code: 053) between 1997 and 2013. Each identified individual with a case of herpes zoster was compared with 1 sex-, age-, and residence-matched control subject. Both groups were followed until the first diagnosis of dementia (ICD-9-CM codes: 290.0 to 290.4, 294.1, 331.0 to 331.2, and 331.82), withdrawal from the registry, or the end of 2013. Cox regression analyses and competing risk model were applied, adjusting for sex, age, residence, depression, autoimmune disease, ischemic stroke, traumatic brain injury, alcohol use disorder, and antiviral treatments for herpes zoster to evaluate the risk of interest. A total of 39,205 cases with herpes zoster were identified. Of the 78,410 study and comparison subjects, 4,204 were diagnosed as having dementia during a mean (SD) follow-up period of 6.22 (4.05) years. Herpes zoster was associated with a slightly increased risk of dementia in the fully adjusted model (hazard ratio [HR] = 1.11; 95% CI, 1.04-1.17). Prescriptions of antiviral therapy were associated with a reduced risk of developing dementia following the diagnosis of herpes zoster (HR = 0.55; 95% CI, 0.40-0.77). Herpes zoster was associated with an increased risk of dementia, independent of potential confounding factors. Antiviral treatment might be protective in preventing dementia in patients with herpes zoster. © Copyright 2017 Physicians Postgraduate Press, Inc.

Immunogenicity and Safety of an Adjuvanted Herpes Zoster Subunit Vaccine Coadministered With Seasonal Influenza Vaccine in Adults Aged 50 Years or Older.

PubMed

Schwarz, Tino F; Aggarwal, Naresh; Moeckesch, Beate; Schenkenberger, Isabelle; Claeys, Carine; Douha, Martine; Godeaux, Olivier; Grupping, Katrijn; Heineman, Thomas C; Fauqued, Marta Lopez; Oostvogels, Lidia; Van den Steen, Peter; Lal, Himal

2017-12-12

The immunogenicity and safety of an adjuvanted herpes zoster subunit (HZ/su) vaccine when coadministered with a quadrivalent seasonal inactivated influenza vaccine (IIV4) was investigated in a phase 3, open-label, randomized clinical trial in adults aged ≥50 years. Subjects were randomized 1:1 to receive either HZ/su (varicella zoster virus glycoprotein E; AS01B Adjuvant System) and IIV4 at day 0 followed by a second HZ/su dose at month 2 (coadministration group), or IIV4 at month 0 and HZ/su at months 2 and 4 (control group). The primary objectives were the HZ/su vaccine response rate in the coadministration group and the noninferiority of the antibody responses to HZ/su and IIV4 in the coadministration compared with the control group. Safety information was collected throughout the duration of the study. A total of 413 subjects were vaccinated in the coadministration group and 415 in the control group. The HZ/su vaccine response rate in the coadministration group was 95.8% (95% confidence interval, 93.3%-97.6%) and the anti-glycoprotein E GMCControl/Coadmin ratio was 1.08 (.97-1.20). The primary noninferiority objectives were met. No safety concerns were observed. No interference in the immune responses to either vaccine was observed when the vaccines were coadministered, and no safety concerns were identified. NCT01954251. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Fold rise in antibody titers by measured by glycoprotein-based enzyme-linked immunosorbent assay is an excellent correlate of protection for a herpes zoster vaccine, demonstrated via the vaccine efficacy curve.

PubMed

Gilbert, Peter B; Gabriel, Erin E; Miao, Xiaopeng; Li, Xiaoming; Su, Shu-Chih; Parrino, Janie; Chan, Ivan S F

2014-11-15

The phase III Zostavax Efficacy and Safety Trial of 1 dose of licensed zoster vaccine (ZV; Zostavax; Merck) in 50-59-year-olds showed approximately 70% vaccine efficacy (VE) to reduce the incidence of herpes zoster (HZ). An objective of the trial was to assess immune response biomarkers measuring antibodies to varicella zoster virus (VZV) by glycoprotein-based enzyme-linked immunosorbent assay as correlates of protection (CoPs) against HZ. The principal stratification vaccine efficacy curve framework for statistically evaluating immune response biomarkers as CoPs was applied. The VE curve describes how VE against the clinical end point (HZ) varies across participant subgroups defined by biomarker readout measuring vaccine-induced immune response. The VE curve was estimated using several subgroup definitions. The fold rise in VZV antibody titers from the time before immunization to 6 weeks after immunization was an excellent CoP, with VE increasing sharply with fold rise: VE was estimated at 0% for the subgroup with no rise and at 90% for the subgroup with 5.26-fold rise. In contrast, VZV antibody titers measured 6 weeks after immunization did not predict VE, with similar estimated VEs across titer subgroups. The analysis illustrates the value of the VE curve framework for assessing immune response biomarkers as CoPs in vaccine efficacy trials. NCT00534248. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

The value of routine polymerase chain reaction analysis of intraocular fluid specimens in the diagnosis of infectious posterior uveitis.

PubMed

Scheepers, Marius A; Lecuona, Karin A; Rogers, Graeme; Bunce, Catey; Corcoran, Craig; Michaelides, Michel

2013-01-01

To assess the value of routine polymerase chain reaction (PCR) analysis on intraocular fluid from patients presenting with a first episode of suspected active infectious posterior uveitis in a population with a high prevalence of human immunodeficiency virus infection. Retrospective, interventional case series. Participants. 159 consecutive patients presenting at a tertiary care hospital over a five-year period. PCR analysis was performed for cytomegalovirus, varicella zoster virus, herpes simplex virus types 1 and 2, Toxoplasma gondii, and Mycobacterium tuberculosis. PCR analysis confirmed the initial clinical diagnosis in 55 patients (35%) and altered the initial clinical diagnosis in 36 patients (23%). The clinical diagnosis prior to PCR testing was nonspecific (uncertain) in 51 patients (32%), with PCR providing a definitive final diagnosis in 20 of these patients (39%); necrotizing herpetic retinopathy and ocular toxoplasmosis were particularly difficult to diagnose correctly without the use of PCR analysis. The clinical phenotype alone was unreliable in diagnosing the underlying infectious cause in a quarter of patients in this study. Since the outcome of incorrectly treated infective uveitis can be blinding, PCR analysis of ocular fluids is recommended early in the disease even in resource poor settings.

The High Prevalence of the Varicella Zoster Virus in Patients With Relapsing-Remitting Multiple Sclerosis: A Case-Control Study in the North of Iran

PubMed Central

Najafi, Saeideh; Ghane, Masood; Yousefzadeh-Chabok, Shahrokh; Amiri, Mehdi

2016-01-01

Background Multiple sclerosis (MS) is the most common neurological autoimmune disease, characterized by multifocal areas of inflammatory demyelination within the central nervous system. It has been hypothesized that the stimulation of the immune system by viral infections is the leading cause of MS among susceptible individuals. Objectives The aim of this study was to investigate the prevalence of the varicella zoster virus (VZV) in patients with relapsing-remitting multiple sclerosis. Patients and Methods Plasma and peripheral blood mononuclear cells (PBMCs) collected from MS patients (n = 82) and controls (n = 89) were screened for the presence of anti-VZV antibodies and VZV DNA by the ELISA and PCR methods. DNA was extracted from all samples, and VZV infection was examined by the PCR technique. Statistical analysis was used to investigate the frequency of the virus in MS patients and a healthy control group. Results Of all the MS patients, 78 (95.1%) and 21 (25.6%) were positive for anti-VZV and VZV DNA, respectively. Statistical analysis of the PCR results showed a significant correlation between the abundance of VZV and MS disease (P < 0.001). However, there was no significant correlation between the abundance of anti-VZV antibodies and MS disease by the ELISA method. Conclusions These results support the hypothesis that VZV may contribute to MS in establishing a systemic infection process and inducing an immune response. PMID:27226879

Varicella infection in a non-universally vaccinated population: Actual epidemiology in Bulgaria (2013-2015).

PubMed

Todorova, Tatina T

Varicella is a common and usually mild disease but it has great importance in regard to general infectious morbidity. The current study aimed to characterize possible risk factors of varicella epidemiology in Bulgaria, a country where infection follows its natural epidemiological pattern as no mandatory or recommended vaccine is currently applied. Administrative regions of Bulgaria were used as units of observation and a set of sociodemographic and economic determinants, as well as geographic location (south or north) were tested for associations with the mean 3-year varicella incidence rates (2013-2015). The proportion of urban population, proportion of females, number of health care units and proportion of urban population aged <10 years were the four sociodemographic variables most strongly and significantly correlated (p<0.05) with varicella frequency (Spearman's rank correlation coefficients of 0.62, 0.47, 0.43, and 0.38, respectively). After reducing the number of intercorrelated factors to a few principal components and accounting for confounders, the demographic component and geographic location remained most robustly associated with varicella incidence in Bulgaria (adjusted R 2 of 0.51, p<0.001). The results obtained identify important determinants in the local epidemiology of varicella and show that community characteristics should be considered, to improve our understanding of varicella distribution. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

Efficacy of an adjuvanted herpes zoster subunit vaccine in older adults.

PubMed

Lal, Himal; Cunningham, Anthony L; Godeaux, Olivier; Chlibek, Roman; Diez-Domingo, Javier; Hwang, Shinn-Jang; Levin, Myron J; McElhaney, Janet E; Poder, Airi; Puig-Barberà, Joan; Vesikari, Timo; Watanabe, Daisuke; Weckx, Lily; Zahaf, Toufik; Heineman, Thomas C

2015-05-28

In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

Vaccine profile of herpes zoster (HZ/su) subunit vaccine.

PubMed

Cunningham, Anthony L; Heineman, Thomas

2017-07-01

Herpes zoster (HZ) causes an often severe and painful rash in older people and may be complicated by prolonged pain (postherpetic neuralgia; PHN) and by dissemination in immune-compromised patients. HZ results from reactivation of latent varicella-zoster virus (VZV) infection, often associated with age-related or other causes of decreased T cell immunity. A live attenuated vaccine boosts this immunity and provides partial protection against HZ, but this decreases with age and declines over 8 years. Areas covered: A new HZ subunit (HZ/su) vaccine combines a key surface VZV glycoprotein (E) with a T cell-boosting adjuvant system (AS01 B ) and is administered by two intramuscular injections two months apart. Expert commentary: HZ/su showed excellent efficacy of ~90% in immunocompetent adults ≥50 and ≥70 years of age, respectively, in the ZOE-50 and ZOE-70 phase III controlled trials. Efficacy was unaffected by advancing age and persisted for >3 years. Approximately 9.5% of subjects had severe, but transient (1-2 days) injection site pain, swelling or redness. Compliance with both vaccine doses was high (95%). The vaccine will have a major impact on HZ management. Phase I-II trials showed safety and immunogenicity in severely immunocompromised patients. Phase III trial results are expected soon.

Detection of Vero Cells Infected with Herpes Simplex Types 1 and 2 and Varicella Zoster Viruses Using Raman Spectroscopy and Advanced Statistical Methods.

PubMed

Huleihel, Mahmoud; Shufan, Elad; Zeiri, Leila; Salman, Ahmad

2016-01-01

Of the eight members of the herpes family of viruses, HSV1, HSV2, and varicella zoster are the most common and are mainly involved in cutaneous disorders. These viruses usually are not life-threatening, but in some cases they might cause serious infections to the eyes and the brain that can lead to blindness and possibly death. An effective drug (acyclovir and its derivatives) is available against these viruses. Therefore, early detection and identification of these viral infections is highly important for an effective treatment. Raman spectroscopy, which has been widely used in the past years in medicine and biology, was used as a powerful spectroscopic tool for the detection and identification of these viral infections in cell culture, due to its sensitivity, rapidity and reliability. Our results showed that it was possible to differentiate, with a 97% identification success rate, the uninfected Vero cells that served as a control, from the Vero cells that were infected with HSV-1, HSV-2, and VZV. For that, linear discriminant analysis (LDA) was performed on the Raman spectra after principal component analysis (PCA) with a leave one out (LOO) approach. Raman spectroscopy in tandem with PCA and LDA enable to differentiate among the different herpes viral infections of Vero cells in time span of few minutes with high accuracy rate. Understanding cell molecular changes due to herpes viral infections using Raman spectroscopy may help in early detection and effective treatment.

Functional decline and herpes zoster in older people: an interplay of multiple factors.

PubMed

2015-12-01

Herpes zoster is a frequent painful infectious disease whose incidence and severity increase with age. In older people, there is a strong bidirectional link between herpes zoster and functional decline, which refers to a decrement in ability to perform activities of daily living due to ageing and disabilities. However, the exact nature of such link remains poorly established. Based on the opinion from a multidisciplinary group of experts, we here propose a new model to account for the interplay between infection, somatic/psychiatric comorbidity, coping skills, polypharmacy, and age, which may account for the functional decline related to herpes zoster in older patients. This model integrates the risk of decompensation of underlying disease; the risk of pain becoming chronic (e.g. postherpetic neuralgia); the risk of herpes zoster non-pain complications; the detrimental impact of herpes zoster on quality of life, functioning, and mood; the therapeutic difficulties due to multimorbidity, polypharmacy, and ageing; and the role of stressful life events in the infection itself and comorbid depression. This model underlines the importance of early treatment, strengthening coping, and vaccine prevention.

Validity of a reported history of chickenpox in targeting varicella vaccination at susceptible adolescents in England☆

PubMed Central

Field, Nigel; Amirthalingam, Gayatri; Waight, Pauline; Andrews, Nick; Ladhani, Shamez N.; van Hoek, Albert Jan; Maple, Peter A.C.; Brown, Kevin E.; Miller, Elizabeth

2014-01-01

Introduction In the UK, primary varicella is usually a mild infection in children, but can cause serious illness in susceptible pregnant women and adults. The UK Joint Committee on Vaccination and Immunisation is considering an adolescent varicella vaccination programme. Cost-effectiveness depends upon identifying susceptibles and minimising vaccine wastage, and chickenpox history is one method to screen for eligibility. To inform this approach, we estimated the proportion of adolescents with varicella antibodies by reported chickenpox history. Methods Recruitment occurred through secondary schools in England from February to September 2012. Parents were asked about their child's history of chickenpox, explicitly setting the context in terms of the implications for vaccination. 247 adolescents, whose parents reported positive (120), negative (77) or uncertain (50) chickenpox history provided oral fluid for varicella zoster virus-specific immunoglobulin-G (VZV-IgG) testing. Results 109 (90.8% [85.6–96.0%]) adolescents with a positive chickenpox history, 52 (67.5% [57.0–78.1%]) with a negative history and 42 (84.0% [73.7–94.3%]) with an uncertain history had VZV-IgG suggesting prior infection. Combining negative and uncertain histories, 74% had VZV-IgG (best-case). When discounting low total-IgG samples and counting equivocals as positive (worst-case), 84% had VZV-IgG. We also modelled outcomes by varying the negative predictive value (NPV) for the antibody assay, and found 74–87% under the best-case and 84–92% under the worst-case scenario would receive vaccine unnecessarily as NPV falls to 50%. Conclusion Reported chickenpox history discriminates between varicella immunity and susceptibility in adolescents, but significant vaccine wastage would occur if this approach alone were used to determine vaccine eligibility. A small but important proportion of those with positive chickenpox history would remain susceptible. These data are needed to determine

Validity of a reported history of chickenpox in targeting varicella vaccination at susceptible adolescents in England.

PubMed

Field, Nigel; Amirthalingam, Gayatri; Waight, Pauline; Andrews, Nick; Ladhani, Shamez N; van Hoek, Albert Jan; Maple, Peter A C; Brown, Kevin E; Miller, Elizabeth

2014-02-26

In the UK, primary varicella is usually a mild infection in children, but can cause serious illness in susceptible pregnant women and adults. The UK Joint Committee on Vaccination and Immunisation is considering an adolescent varicella vaccination programme. Cost-effectiveness depends upon identifying susceptibles and minimising vaccine wastage, and chickenpox history is one method to screen for eligibility. To inform this approach, we estimated the proportion of adolescents with varicella antibodies by reported chickenpox history. Recruitment occurred through secondary schools in England from February to September 2012. Parents were asked about their child's history of chickenpox, explicitly setting the context in terms of the implications for vaccination. 247 adolescents, whose parents reported positive (120), negative (77) or uncertain (50) chickenpox history provided oral fluid for varicella zoster virus-specific immunoglobulin-G (VZV-IgG) testing. 109 (90.8% [85.6-96.0%]) adolescents with a positive chickenpox history, 52 (67.5% [57.0-78.1%]) with a negative history and 42 (84.0% [73.7-94.3%]) with an uncertain history had VZV-IgG suggesting prior infection. Combining negative and uncertain histories, 74% had VZV-IgG (best-case). When discounting low total-IgG samples and counting equivocals as positive (worst-case), 84% had VZV-IgG. We also modelled outcomes by varying the negative predictive value (NPV) for the antibody assay, and found 74-87% under the best-case and 84-92% under the worst-case scenario would receive vaccine unnecessarily as NPV falls to 50%. Reported chickenpox history discriminates between varicella immunity and susceptibility in adolescents, but significant vaccine wastage would occur if this approach alone were used to determine vaccine eligibility. A small but important proportion of those with positive chickenpox history would remain susceptible. These data are needed to determine whether reported history, with or without oral fluid

Varicella complicated by scarlet fever.

PubMed

Yavuz, Taner; Parlak, Ali Haydar; Kocabay, Kenan

2003-10-01

We report a 3-year-old boy with varicella complicated by cellulitis and scarlet fever. He developed a typical rash of scarlet fever following the onset of varicella. Streptococcus pyogenes was isolated from the ulcers due to varicella. The present case suggests that scarlet fever may rarely develop following varicella and should be considered in children with complicated varicella.

Vaccination against Herpes Zoster and Postherpetic Neuralgia

PubMed Central

Oxman, Michael N.; Levin, Myron J.

2008-01-01

Background. Herpes zoster (HZ) and postherpetic neuralgia (PHN) cause significant morbidity in older adults. The incidence and severity of HZ and PHN increase with age in association with an age-related decline in varicella-zoster virus (VZV)-specific cell-mediated immunity (VZV-CMI). VZV vaccines can boost VZV-CMI. Therefore, we tested the hypothesis that VZV vaccination would protect older adults against HZ and PHN. Methods. We enrolled 38,546 adults ⩾60 years of age in a randomized, double-blind, placebo-controlled trial of an investigational HZ vaccine and actively followed subjects for the development of HZ. The primary end point was the burden of illness due to HZ (HZ BOI), a composite measure of the incidence, severity, and duration of pain and discomfort caused by HZ. The secondary end point was the incidence of PHN. Results. Subject retention was >95%. HZ vaccine reduced the HZ BOI by 61.1% (95% confidence interval [CI], 51.1%–69.1%; P < .001) and reduced the incidence of PHN by 66.5% (95% CI, 47.5%–79.2%; P < .001). The incidence of HZ was also reduced by 51.3% (95% CI, 44.2%–57.6%; P < .001). HZ vaccine was well tolerated; injection site reactions were generally mild. HZ vaccine neither caused nor induced HZ. Conclusion. The Shingles Prevention Study demonstrated that HZ vaccine significantly reduced the morbidity due to HZ and PHN in older adults. PMID:18419402

Cost-effectiveness of vaccination against herpes zoster.

PubMed

de Boer, Pieter T; Wilschut, Jan C; Postma, Maarten J

2014-01-01

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN.

Cost-effectiveness of vaccination against herpes zoster

PubMed Central

de Boer, Pieter T; Wilschut, Jan C; Postma, Maarten J

2014-01-01

Herpes zoster (HZ) is a common disease among elderly, which may develop into a severe pain syndrome labeled postherpetic neuralgia (PHN). A live-attenuated varicella zoster virus vaccine has been shown to be effective in reducing the incidence and burden of illness of HZ and PHN, providing the opportunity to prevent significant health-related and financial consequences of HZ. In this review, we summarize the available literature on cost-effectiveness of HZ vaccination and discuss critical parameters for cost-effectiveness results. A search in PubMed and EMBASE was performed to identify full cost-effectiveness studies published before April 2013. Fourteen cost-effectiveness studies were included, all performed in western countries. All studies evaluated cost-effectiveness among elderly above 50 years and used costs per quality-adjusted life year (QALY) gained as primary outcome. The vast majority of studies showed vaccination of 60- to 75-year-old individuals to be cost-effective, when duration of vaccine efficacy was longer than 10 years. Duration of vaccine efficacy, vaccine price, HZ incidence, HZ incidence and discount rates were influential to the incremental cost-effectiveness ratio (ICER). HZ vaccination may be a worthwhile intervention from a cost-effectiveness point of view. More extensive reporting on methodology and more detailed results of sensitivity analyses would be desirable to address uncertainty and to guarantee optimal comparability between studies, for example regarding model structure, discounting, vaccine characteristics and loss of quality of life due to HZ and PHN. PMID:25424815

Absent anti-N-methyl-D-aspartate receptor NR1a antibodies in herpes simplex virus encephalitis and varicella zoster virus infections.

PubMed

Berger, Benjamin; Pytlik, Maximilian; Hottenrott, Tilman; Stich, Oliver

2017-02-01

A 2012 report and subsequent case series described anti-N-methyl-D-aspartate receptor (NMDAR) antibodies in patients during the acute phase and relapse of herpes simplex virus 1 (HSV1) encephalitis (HSV1E). However, the prevalence of this phenomenon is unknown and systematic studies on other viral infections of the nervous system are missing. We retrospectively analyzed serial cerebrospinal fluid (CSF) and serum samples of consecutive patients treated for neurological HSV1, HSV2 and varicella zoster virus (VZV) infections in our tertiary care university hospital between 2003 and 2013 for the presence of antibodies directed against the NR1a subunit of the NMDAR using indirect immunofluorescence. In total, 88 patients with the following infections were identified through an electronic database search: HSV1 (24 with encephalitis), HSV2 (6 with meningitis, 3 with encephalitis and 1 with myelitis), or VZV (3 with meningitis, 33 with encephalitis, 17 with radiculitis and 1 with myelitis). Two patients with HSV1E and HSV2E, respectively, experienced a clinical relapse. Clinical follow-up was for up to 85 months, and repetitive serum and CSF analyses for up to 43 months. However, at no time did any of the 88 patients exhibit anti-NMDAR NR1a antibodies. In this study, we did not detect anti-NMDAR NR1a antibodies in serial CSF and serum samples of HSV1E patients or patients with other viral infections (HSV2 and VZV). However, the presence of antibodies directed against other epitopes of the NMDAR and other neuronal cell surface antigens cannot be excluded, necessitating further studies.

A case of anti aquapolin-4 antibody positive myelitis with hyperhidrosis, following herpes zoster.

PubMed

Suda, Machiko; Tsutsumiuchi, Michiko; Uesaka, Yoshikazu; Hayashi, Nobukazu

2017-01-31

We report an acute myelitis in a 53-year-old woman that occurred in 7 days after the diagnosis of Th5-6 herpes zoster. Clinical examination revealed hyperhidrosis of left side of her face, neck, arm and upper chest. She also had muscle weakness of her left leg and sensory impairment for light touch and temperature in her chest and legs. Spinal cord MRI demonstrated a longitudinal T 2 -hyperintense lesion extending from Th1 to 7. In the axial imaging, the lesion dominantly located in the left side gray matter. Hyperhidrosis, weakness and sensory impairment were improved after intravenous therapy with acyclovir and methylprednisolone. VZV (varicella zoster virus) IgG index of the cerebrospinal fluid was high and serological anti aquaporin-4 antibodies were positive at the time of the admission. This case had both characteristics of VZV myelitis and neuromyelitis optica spectrum disorder. Myelitis relapsed 19 months after the first attack. We believe that sympathetic hyper reactivity due to thoracic spinal cord lesion was responsible for the hyperhidrosis in our patient.

Application of Oral Fluid Assays in Support of Mumps, Rubella and Varicella Control Programs.

PubMed

Maple, Peter A C

2015-12-09

Detection of specific viral antibody or nucleic acid produced by infection or immunization, using oral fluid samples, offers increased potential for wider population uptake compared to blood sampling. This methodology is well established for the control of HIV and measles infections, but can also be applied to the control of other vaccine preventable infections, and this review describes the application of oral fluid assays in support of mumps, rubella and varicella national immunization programs. In England and Wales individuals with suspected mumps or rubella, based on clinical presentation, can have an oral fluid swab sample taken for case confirmation. Universal varicella immunization of children has led to a drastic reduction of chickenpox in those countries where it is used; however, in England and Wales such a policy has not been instigated. Consequently, in England and Wales most children have had chickenpox by age 10 years; however, small, but significant, numbers of adults remain susceptible. Targeted varicella zoster virus (VZV) immunization of susceptible adolescents offers the potential to reduce the pool of susceptible adults and oral fluid determination of VZV immunity in adolescents is a potential means of identifying susceptible individuals in need of VZV vaccination. The main application of oral fluid testing is in those circumstances where blood sampling is deemed not necessary, or is undesirable, and when the documented sensitivity and specificity of the oral fluid assay methodology to be used is considered sufficient for the purpose intended.

Routine vaccination against chickenpox?

PubMed

2012-04-01

Varicella-zoster virus (VZV) causes both varicella and herpes zoster. In 1995 a varicella vaccine was licensed in the USA and was incorporated into the routine vaccination programme for children; a decline of varicella among children and adults, and a reduction in associated hospitalisation, complications and mortality, has resulted. In the UK, a policy of targeted vaccination of at-risk groups has been in place since the vaccine was introduced. Here we review the evidence for the different approaches to VZV vaccination policy.

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

PubMed Central

Bosseboeuf, Adrien; Feron, Delphine; Tallet, Anne; Rossi, Cédric; Charlier, Cathy; Garderet, Laurent; Caillot, Denis; Moreau, Philippe; Cardó-Vila, Marina; Pasqualini, Renata; Nelson, Alfreda Destea; Wilson, Bridget S.; Perreault, Hélène; Piver, Eric; Weigel, Pierre; Harb, Jean; Bigot-Corbel, Edith; Hermouet, Sylvie

2017-01-01

Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1–specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection–linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients. PMID:28978808

Ocular complications in patients with lung transplants.

PubMed

Tarabishy, Ahmad B; Khatib, Omar F; Nocero, John R; Budev, Marie; Kaiser, Peter K

2011-09-01

To describe infectious and non-infectious ocular complications found in patients with lung transplants. 545 patients underwent lung transplantation from January 1998 to September 2008 at the Cleveland Clinic. Patients who underwent ophthalmic examination at the Cole Eye Institute after lung transplantation were included in the study. Diagnoses, treatments, surgeries, laboratory parameters of immune status and patient survival were examined. Of the 545 patients who received a lung transplant during the study period at the Cleveland Clinic, 46 (8.4%) patients underwent ophthalmology examination after a lung transplant. The most common ocular finding was posterior subcapsular cataract, found in 13/46 (28.3%) patients. Infectious ocular complications were present in 6/46 patients (13.0%) including fungal infections (rhino-orbital mucormycosis (n=1), disseminated Pseudallescheria boydii infection (n=2)), cytomegalovirus retinitis (n=1), varicella-zoster virus keratouveitis (n=1) and herpes zoster ophthalmicus (n=1). Five of six patients with infectious ocular complications died within 6 months of evaluation. Decreased absolute lymphocyte count was associated with infectious ocular complications (p=0.014). Many ocular conditions can occur in patients with lung transplants. Ocular infectious complications were uncommon but may be associated with increased mortality.

Use of lambdagt11 to isolate genes for two pseudorabies virus glycoproteins with homology to herpes simplex virus and varicella-zoster virus glycoproteins

DOE Office of Scientific and Technical Information (OSTI.GOV)

Petrovskis, E.A.; Timmins, J.G.; Post, L.E.

1986-10-01

A library of pseudorabies virus (PRV) DNA fragments was constructed in the expression cloning vector lambdagt11. The library was screened with antisera which reacted with mixtures of PRV proteins to isolate recombinant bacteriophages expressing PRV proteins. By the nature of the lambdagt11 vector, the cloned proteins were expressed in Escherichia coli as ..beta..-galactosidase fusion proteins. The fusion proteins from 35 of these phages were purified and injected into mice to raise antisera. The antisera were screened by several different assays, including immunoprecipitation of (/sup 14/C)glucosamine-labeled PRV proteins. This method identified phages expressing three different PRV glycoproteins: the secreted glycoprotein, gX;more » gI; and a glycoprotein that had not been previously identified, which we designate gp63. The gp63 and gI genes map adjacent to each other in the small unique region of the PRV genome. The DNA sequence was determined for the region of the genome encoding gp63 and gI. It was found that gp63 has a region of homology with a herpes simplex virus type 1 (HSV-1) protein, encoded by US7, and also with varicella-zoster virus (VZV) gpIV. The gI protein sequence has a region of homology with HSV-1 gE and VZV gpI. It is concluded that PRV, HSV, and VZV all have a cluster of homologous glycoprotein genes in the small unique components of their genomes and that the organization of these genes is conserved.« less

Database of Autotransplants for Breast Cancer.

DTIC Science & Technology

1998-11-01

atypical bacteria in Q.79, 81.) 301 Herpes Simplex (HSV1, HSV2) 100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Varicella...100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Varicella) 101 Coxiella 303 Cytomegalovirus (CMV) 102 Legionella 304...atypical bacteria in Q.329, 330.) 301 Herpes Simplex (HSV1, HSV2) 100 Atypical bacteria, not otherwise specified 302 Herpes Zoster ( Chicken pox , Vadcella

Efficacy, safety, and tolerability of herpes zoster vaccine in persons aged 50-59 years.

PubMed

Schmader, Kenneth E; Levin, Myron J; Gnann, John W; McNeil, Shelly A; Vesikari, Timo; Betts, Robert F; Keay, Susan; Stek, Jon E; Bundick, Nickoya D; Su, Shu-Chih; Zhao, Yanli; Li, Xiaoming; Chan, Ivan S F; Annunziato, Paula W; Parrino, Janie

2012-04-01

Herpes zoster (HZ) adversely affects individuals aged 50-59, but vaccine efficacy has not been assessed in this population. This study was designed to determine the efficacy, safety, and tolerability of zoster vaccine for preventing HZ in persons aged 50-59 years. This was a randomized, double-blind, placebo-controlled study of 22 439 subjects aged 50-59 years conducted in North America and Europe. Subjects were given 1 dose of licensed zoster vaccine (ZV) (Zostavax; Merck) and followed for occurrence of HZ for ≥1 year (mean, 1.3 years) postvaccination until accrual of ≥96 confirmed HZ cases (as determined by testing lesions swabs for varicella zoster virus DNA by polymerase chain reaction). Subjects were followed for all adverse events (AEs) from day 1 to day 42 postvaccination and for serious AEs (SAEs) through day 182 postvaccination. The ZV reduced the incidence of HZ (30 cases in vaccine group, 1.99/1000 person-years vs 99 cases in placebo group, 6.57/1000 person-years). Vaccine efficacy for preventing HZ was 69.8% (95% confidence interval, 54.1-80.6). AEs were reported by 72.8% of subjects in the ZV group and 41.5% in the placebo group, with the difference primarily due to higher rates of injection-site AEs and headache. The proportion of subjects reporting SAEs occurring within 42 days postvaccination (ZV, 0.6%; placebo, 0.5%) and 182 days postvaccination (ZV, 2.1%; placebo, 1.9%) was similar between groups. In subjects aged 50-59 years, the ZV significantly reduced the incidence of HZ and was well tolerated. NCT00534248.

Progressive outer retinal necrosis and immunosuppressive therapy in myasthenia gravis.

PubMed

Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

2014-01-01

Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment.

Risk factors for complicated varicella infection in pediatric oncology patients at a tertiary health care facility in Pakistan.

PubMed

Alam, Muhammad Matloob; Qamar, Farah Naz; Khan, Zalan Wahid; Kumar, Vikram; Mushtaq, Naureen; Fadoo, Zehra

2014-02-13

Varicella zoster infection (VZI) is well recognized as a potential cause of morbidity and mortality in immunocompromised pediatric oncology patients (POP). The purpose of this study was to describe the clinical profile and risk factors for complications and outcomes of VZI in POP treated with acyclovir. Medical records of all POP with a discharge diagnosis of VZI over a period of seven years (2005-2011) were reviewed. The demographic features, underlying malignancy, risk factors for VZI, complications, and outcomes were recorded. Thirty-six POP with VZI were identified. Leukemia was the most common underlying malignancy (n = 20, 58.8%), followed by lymphoma (n = 7, 20.6%) and solid organ tumors (n = 7, 20.6%). Most of the cases (41%) were observed in children under five. All patients were treated with acyclovir. Varicella-related complications developed in 10 (29%) patients. The most frequent complication was bloodstream infection (n = 3, 8.8%), followed by pneumonia (n = 2, 5.9%), skin infection (n = 2, 5.9%), hepatitis, renal failure, and encephalitis. Independent risk factors associated with complications were age < five years, weight for age < fifth percentile, delay in seeking care (> seven days after onset of symptoms) and severe neutropenia (ANC < 500/cm). One child died secondary to varicella encephalitis. Our data suggests that young age, poor health-seeking behavior, severe neutropenia, and being underweight are the major risk factors for the development of varicella-related complications in POP in developing countries. These complications could be favorably modified through active immunization of immunocompetent children.

[Cerebral infarction and intracranial aneurysm related to the reactivation of varicella zoster virus in a Japanese acquired immunodeficiency syndrome (AIDS) patient].

PubMed

Yasuda, Chiharu; Okada, Kazumasa; Ohnari, Norihiro; Akamatsu, Naoki; Tsuji, Sadatoshi

2013-01-01

A 35-years-old right-handed man admitted to our hospital with a worsening of dysarthria, left facial palsy and left hemiparesis for 2 days. Acquired immunodeficiency syndrome (AIDS) was diagnosed when he was 28 years old. At that time, he also was treated for syphilis. After highly active antiretroviral treatment (HAART) was introduced at the age of 35 years old, serum level of human immunodeficiency virus (HIV) was not detected, but the number of CD4+ T cells was still less than 200/μl. He had no risk factors of atherosclerosis including hypertension, diabetes and hyperlipidemia. He had neither coagulation abnormality nor autoimmune disease. Magnetic resonance imaging (MRI) showed acute ischemic infarction spreading from the right corona radiate to the right internal capsule without contrast enhancement. Stenosis and occlusion of intracranial arteries were not detected by MR angiography. Although argatroban and edaravone were administered, his neurological deficits were worsened to be difficult to walk independently. Cerebrospinal fluid (CSF) examination showed a mild mononuclear pleocytosis (16/μl).　Oligoclonal band was positive. The titer of anti-varicella zoster virus (VZV) IgG antibodies was increased, that indicated VZV reactivation in the central nervous system (CNS), although VZV DNA PCR was not detected. Therefore, acyclovir (750 mg/day for 2 weeks) and valaciclovir (3,000 mg/day for 1 month) were administered in addition to stroke therapy. He recovered to be able to walk independently 2 month after the admission.Angiography uncovered a saccular aneurysm of 3 mm at the end of branch artery of right anterior cerebral artery, Heubner artery, 28 days after the admission. We speculated that VZV vasculopathy caused by VZV reactivation in CNS was involved in the pathomechanism of cerebral infarction rather than HIV vasculopathy in the case.

Economic evaluations of varicella vaccination programmes: a review of the literature.

PubMed

Thiry, Nancy; Beutels, Philippe; Van Damme, Pierre; Van Doorslaer, Eddy

2003-01-01

final recommendations can be made. First, more transparency, completeness and compliance to general methodological guidelines are required. Second, because of the increasing severity of varicella with age, it is preferable and in some cases essential to use dynamic models for the assessment of universal vaccination strategies. Third, most studies focused on the strategy of vaccinating children only while their results depended heavily on disputable assumptions (regarding vaccine effectiveness and impact on herpes zoster). Since violation of these assumptions could have important adverse public health effects, we suggest pre-adolescent vaccination as a more secure alternative. This option deserves more attention in future analyses.

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older.

PubMed

Cunningham, Anthony L; Lal, Himal; Kovac, Martina; Chlibek, Roman; Hwang, Shinn-Jang; Díez-Domingo, Javier; Godeaux, Olivier; Levin, Myron J; McElhaney, Janet E; Puig-Barberà, Joan; Vanden Abeele, Carline; Vesikari, Timo; Watanabe, Daisuke; Zahaf, Toufik; Ahonen, Anitta; Athan, Eugene; Barba-Gomez, Jose F; Campora, Laura; de Looze, Ferdinandus; Downey, H Jackson; Ghesquiere, Wayne; Gorfinkel, Iris; Korhonen, Tiina; Leung, Edward; McNeil, Shelly A; Oostvogels, Lidia; Rombo, Lars; Smetana, Jan; Weckx, Lily; Yeo, Wilfred; Heineman, Thomas C

2016-09-15

A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. In our

Clinical and Microbiological Characteristics of Invasive Group A Streptococcal Infections Before and After Implementation of a Universal Varicella Vaccine Program.

PubMed

Frère, Julie; Bidet, Philippe; Tapiéro, Bruce; Rallu, Fabien; Minodier, Philippe; Bonacorsi, Stephane; Bingen, Edouard; Ovetchkine, Philippe

2016-01-01

Since the introduction of the varicella vaccine to the routine immunization schedule, we have observed a 70% reduction in the rate of varicella-associated invasive group A streptococcal infections (IGASI). In the mean time, the clinical presentation of IGASI and microbiological characteristics of GAS strains have changed significantly. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Shingles - aftercare

MedlinePlus

Herpes zoster - treatment ... Mays RM, Petersen ET, Gordon RA, Tyring SK. Herpes zoster. In: Lebwohl MG, Heymann WR, Berth-Jones ... Saunders; 2014:chap 101. Whitley RJ. Chickenpox and herpes zoster (varicella-zoster virus). In: Bennett JE, Dolin ...

Safety of Zoster Vaccine in Elderly Adults Following Documented Herpes Zoster

PubMed Central

Morrison, Vicki A.; Oxman, Michael N.; Levin, Myron J.; Schmader, Kenneth E.; Guatelli, John C.; Betts, Robert F.; Gelb, Larry D.; Pachucki, Constance T.; Keay, Susan K.; Menzies, Barbara; Griffin, Marie R.; Kauffman, Carol A.; Marques, Adriana R.; Toney, John F.; Simberkoff, Michael S.; Serrao, Richard; Arbeit, Robert D.; Gnann, John W.; Greenberg, Richard N.; Holodniy, Mark; Keitel, Wendy A.; Yeh, Shingshing S.; Davis, Larry E.; Crawford, George E.; Neuzil, Kathy M.; Johnson, Gary R.; Zhang, Jane H.; Harbecke, Rith; Chan, Ivan S. F.; Keller, Paul M.; Williams, Heather M.; Boardman, Kathy D.; Silber, Jeffrey L.; Annunziato, Paula W.

2013-01-01

Background. After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). Methods. A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. Results. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3–85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. Conclusions. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥60 years of age with no contraindications, regardless of a prior history of HZ. PMID:23633406

Safety of zoster vaccine in elderly adults following documented herpes zoster.

PubMed

Morrison, Vicki A; Oxman, Michael N; Levin, Myron J; Schmader, Kenneth E; Guatelli, John C; Betts, Robert F; Gelb, Larry D; Pachucki, Constance T; Keay, Susan K; Menzies, Barbara; Griffin, Marie R; Kauffman, Carol A; Marques, Adriana R; Toney, John F; Simberkoff, Michael S; Serrao, Richard; Arbeit, Robert D; Gnann, John W; Greenberg, Richard N; Holodniy, Mark; Keitel, Wendy A; Yeh, Shingshing S; Davis, Larry E; Crawford, George E; Neuzil, Kathy M; Johnson, Gary R; Zhang, Jane H; Harbecke, Rith; Chan, Ivan S F; Keller, Paul M; Williams, Heather M; Boardman, Kathy D; Silber, Jeffrey L; Annunziato, Paula W

2013-08-15

After completion of the Shingles Prevention Study (SPS; Department of Veterans Affairs Cooperative Studies Program Number 403), SPS participants who had initially received placebo were offered investigational zoster vaccine without charge. This provided an opportunity to determine the relative safety of zoster vaccine in older adults following documented herpes zoster (HZ). A total of 13 681 SPS placebo recipients who elected to receive zoster vaccine were followed for serious adverse events (SAE) for 28 days after vaccination. In contrast to the SPS, a prior episode of HZ was not a contraindication to receiving zoster vaccine. The SPS placebo recipients who received zoster vaccine included 420 who had developed documented HZ during the SPS. The mean interval between the onset of HZ and the receipt of zoster vaccine in the 420 recipients with prior HZ was 3.61 years (median interval, 3.77 years [range, 3-85 months]); the interval was <5 years for approximately 80% of recipients. The proportion of vaccinated SPS placebo recipients with prior HZ who developed ≥ 1 SAE (0.95%) was not significantly different from that of vaccinated SPS placebo recipients with no prior history of HZ (0.66%), and the distribution of SAEs in the 2 groups was comparable. These results demonstrate that the general safety of zoster vaccine in older persons is not altered by a recent history of documented HZ, supporting the safety aspect of the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices recommendation to administer zoster vaccine to all persons ≥ 60 years of age with no contraindications, regardless of a prior history of HZ.

Varicella routine vaccination and the effects on varicella epidemiology – results from the Bavarian Varicella Surveillance Project (BaVariPro), 2006-2011

PubMed Central

2013-01-01

Background In 2004, routine varicella vaccination was recommended in Germany for children 11-14 months of age with one dose, and since 2009, with a second dose at 15-23 months of age. The effects on varicella epidemiology were investigated. Methods Data on varicella vaccinations, cases and complications were collected from annual parent surveys (2006-2011), monthly paediatric practice surveillance (Oct 2006 - Sep 2011; five varicella seasons) and paediatric hospital databases (2005-2009) in the area of Munich (about 238,000 paediatric inhabitants); annual incidences of cases and hospitalisations were estimated. Results Varicella vaccination coverage (1st dose) in children 18-36 months of age increased in two steps (38%, 51%, 53%, 53%, 66% and 68%); second-dose coverage reached 59% in the 2011 survey. A monthly mean of 82 (62%) practices participated; they applied a total of 50,059 first-dose and 40,541 second-dose varicella vaccinations, with preferential use of combined MMR-varicella vaccine after recommendation of two doses, and reported a total of 16,054 varicella cases <17 years of age. The mean number of cases decreased by 67% in two steps, from 6.6 (95%CI 6.1-7.0) per 1,000 patient contacts in season 2006/07 to 4.2 (95%CI 3.9-4.6) in 2007/08 and 4.0 (95%CI 3.6-4.3) in 2008/09, and further to 2.3 (95%CI 2.0-2.6) in 2009/10 and 2.2 (95%CI 1.9-2.5) in 2010/11. The decrease occurred in all paediatric age groups, indicating herd protection effects. Incidence of varicella was estimated as 78/1,000 children <17 years of age in 2006/07, and 19/1,000 in 2010/11. Vaccinated cases increased from 0.3 (95%0.2-0.3) per 1,000 patient contacts in 2006/07 to 0.4 (95%CI 0.3-0.5) until 2008/09 and decreased to 0.2 (95%CI 0.2-0.3) until 2010/11. The practices treated a total of 134 complicated cases, mainly with skin complications. The paediatric hospitals recorded a total of 178 varicella patients, including 40 (22.5%) with neurological complications and one (0.6%) fatality due

Active Learning to Understand Infectious Disease Models and Improve Policy Making

PubMed Central

Vladislavleva, Ekaterina; Broeckhove, Jan; Beutels, Philippe; Hens, Niel

2014-01-01

Modeling plays a major role in policy making, especially for infectious disease interventions but such models can be complex and computationally intensive. A more systematic exploration is needed to gain a thorough systems understanding. We present an active learning approach based on machine learning techniques as iterative surrogate modeling and model-guided experimentation to systematically analyze both common and edge manifestations of complex model runs. Symbolic regression is used for nonlinear response surface modeling with automatic feature selection. First, we illustrate our approach using an individual-based model for influenza vaccination. After optimizing the parameter space, we observe an inverse relationship between vaccination coverage and cumulative attack rate reinforced by herd immunity. Second, we demonstrate the use of surrogate modeling techniques on input-response data from a deterministic dynamic model, which was designed to explore the cost-effectiveness of varicella-zoster virus vaccination. We use symbolic regression to handle high dimensionality and correlated inputs and to identify the most influential variables. Provided insight is used to focus research, reduce dimensionality and decrease decision uncertainty. We conclude that active learning is needed to fully understand complex systems behavior. Surrogate models can be readily explored at no computational expense, and can also be used as emulator to improve rapid policy making in various settings. PMID:24743387

Active learning to understand infectious disease models and improve policy making.

PubMed

Willem, Lander; Stijven, Sean; Vladislavleva, Ekaterina; Broeckhove, Jan; Beutels, Philippe; Hens, Niel

2014-04-01

Modeling plays a major role in policy making, especially for infectious disease interventions but such models can be complex and computationally intensive. A more systematic exploration is needed to gain a thorough systems understanding. We present an active learning approach based on machine learning techniques as iterative surrogate modeling and model-guided experimentation to systematically analyze both common and edge manifestations of complex model runs. Symbolic regression is used for nonlinear response surface modeling with automatic feature selection. First, we illustrate our approach using an individual-based model for influenza vaccination. After optimizing the parameter space, we observe an inverse relationship between vaccination coverage and cumulative attack rate reinforced by herd immunity. Second, we demonstrate the use of surrogate modeling techniques on input-response data from a deterministic dynamic model, which was designed to explore the cost-effectiveness of varicella-zoster virus vaccination. We use symbolic regression to handle high dimensionality and correlated inputs and to identify the most influential variables. Provided insight is used to focus research, reduce dimensionality and decrease decision uncertainty. We conclude that active learning is needed to fully understand complex systems behavior. Surrogate models can be readily explored at no computational expense, and can also be used as emulator to improve rapid policy making in various settings.

Herpes zoster vaccine in older adults and the risk of subsequent herpes zoster disease.

PubMed

Tseng, Hung Fu; Smith, Ning; Harpaz, Rafael; Bialek, Stephanie R; Sy, Lina S; Jacobsen, Steven J

2011-01-12

Approximately 1 million episodes of herpes zoster occur annually in the United States. Although prelicensure data provided evidence that herpes zoster vaccine works in a select study population under idealized circumstances, the vaccine needs to be evaluated in field conditions. To evaluate risk of herpes zoster after receipt of herpes zoster vaccine among individuals in general practice settings. A retrospective cohort study from January 1, 2007, through December 31, 2009, of individuals enrolled in the Kaiser Permanente Southern California health plan. Participants were immunocompetent community-dwelling adults aged 60 years or older. The 75,761 members in the vaccinated cohort were age matched (1:3) to 227,283 unvaccinated members. Incidence of herpes zoster. Herpes zoster vaccine recipients were more likely to be white, women, with more outpatient visits, and fewer chronic diseases. The number of herpes zoster cases among vaccinated individuals was 828 in 130,415 person-years (6.4 per 1000 person-years; 95% confidence interval [CI], 5.9-6.8), and for unvaccinated individuals it was 4606 in 355,659 person-years (13.0 per 1000 person-years; 95% CI, 12.6-13.3). In adjusted analysis, vaccination was associated with a reduced risk of herpes zoster (hazard ratio [HR], 0.45; 95% CI, 0.42-0.48); this reduction occurred in all age strata and among individuals with chronic diseases. Risk of herpes zoster differed by vaccination status to a greater magnitude than the risk of unrelated acute medical conditions, suggesting results for herpes zoster were not due to bias. Ophthalmic herpes zoster (HR, 0.37; 95% CI, 0.23-0.61) and hospitalizations coded as herpes zoster (HR, 0.35; 95% CI, 0.24-0.51) were less likely among vaccine recipients. Among immunocompetent community-dwelling adults aged 60 years or older, receipt of the herpes zoster vaccine was associated with a lower incidence of herpes zoster. The risk was reduced among all age strata and among individuals with

The impact of varicella vaccination on varicella-related hospitalization rates: global data review

PubMed Central

Hirose, Maki; Gilio, Alfredo Elias; Ferronato, Angela Esposito; Ragazzi, Selma Lopes Betta

2016-01-01

Abstract Objective: To describe the impact of varicella vaccination on varicella-related hospitalization rates in countries that implemented universal vaccination against the disease. Data source: We identified countries that implemented universal vaccination against varicella at the http://apps.who.int/immunization_monitoring/globalsummary/schedules site of the World Health Organization and selected articles in Pubmed describing the changes (pre/post-vaccination) in the varicella-related hospitalization rates in these countries, using the Keywords "varicella", "vaccination/vaccine" and "children" (or) "hospitalization". Publications in English published between January 1995 and May 2015 were included. Data synthesis: 24 countries with universal vaccination against varicella and 28 articles describing the impact of the vaccine on varicella-associated hospitalizations rates in seven countries were identified. The US had 81.4%–99.2% reduction in hospitalization rates in children younger than four years, 6–14 years after the onset of universal vaccination (1995), with vaccination coverage of 90%; Uruguay: 94% decrease (children aged 1–4 years) in six years, vaccination coverage of 90%; Canada: 93% decrease (age 1–4 years) in 10 years, coverage of 93%; Germany: 62.4% decrease (age 1–4 years) in 8 years, coverage of 78.2%; Australia: 76.8% decrease (age 1–4 years) in 5 years, coverage of 90%; Spain: 83.5% decrease (age <5 years) in four years, coverage of 77.2% and Italy 69.7%–73.8% decrease (general population), coverage of 60%–95%. Conclusions: The publications showed variations in the percentage of decrease in varicella-related hospitalization rates after universal vaccination in the assessed countries; the results probably depend on the time since the implementation of universal vaccination, differences in the studied age group, hospital admission criteria, vaccination coverage and strategy, which does not allow direct comparison between data. PMID

The impact of varicella vaccination on varicella-related hospitalization rates: global data review.

PubMed

Hirose, Maki; Gilio, Alfredo Elias; Ferronato, Angela Esposito; Ragazzi, Selma Lopes Betta

2016-09-01

to describe the impact of varicella vaccination on varicella-related hospitalization rates in countries that implemented universal vaccination against the disease. we identified countries that implemented universal vaccination against varicella at the http://apps.who.int/immunization_monitoring/globalsummary/schedules site of the World Health Organization and selected articles in Pubmed describing the changes (pre/post-vaccination) in the varicella-related hospitalization rates in these countries, using the Keywords "varicella", "vaccination/vaccine" and "children" (or) "hospitalization". Publications in English published between January 1995 and May 2015 were included. 24 countries with universal vaccination against varicella and 28 articles describing the impact of the vaccine on varicella-associated hospitalizations rates in seven countries were identified. The US had 81.4% -99.2% reduction in hospitalization rates in children younger than four years after 6-14 years after the onset of universal vaccination (1995), with vaccination coverage of 90%; Uruguay: 94% decrease (children aged 1-4 years) in six years, vaccination coverage of 90%; Canada: 93% decrease (age 1-4 years) in 10 years, coverage of 93%; Germany: 62.4% decrease (age 1-4 years) in 8 years, coverage of 78.2%; Australia: 76.8% decrease (age 1-4 years) in 5 years, coverage of 90%; Spain: 83.5% decrease (age <5 years) in four years, coverage of 77.2% and Italy 69.7% -73.8% decrease (general population), coverage of 60%-95%. The publications showed variations in the percentage of decrease in varicella-related hospitalization rates after universal vaccination in the assessed countries; the results probably depend on the time since the implementation of universal vaccination, differences in the studied age group, hospital admission criteria, vaccination coverage and strategy, which does not allow direct comparison between data. Copyright © 2016 Sociedade de Pediatria de São Paulo. Publicado por

Safety and immunogenicity of an adjuvanted herpes zoster subunit candidate vaccine in HIV-infected adults: a phase 1/2a randomized, placebo-controlled study.

PubMed

Berkowitz, Elchonon M; Moyle, Graeme; Stellbrink, Hans-Jürgen; Schürmann, Dirk; Kegg, Stephen; Stoll, Matthias; El Idrissi, Mohamed; Oostvogels, Lidia; Heineman, Thomas C

2015-04-15

Human immunodeficiency virus (HIV)-infected individuals are at increased risk of herpes zoster (HZ), even in the antiretroviral therapy (ART) era. Because concerns exist about the use of live-attenuated vaccines in immunocompromised individuals, a subunit vaccine may be an appropriate alternative. This phase 1/2, randomized, placebo-controlled study evaluated the immunogenicity and safety of an investigational HZ subunit vaccine (HZ/su). Three cohorts of HIV-infected adults aged ≥18 years were enrolled: 94 ART recipients with a CD4(+) T-cell count of ≥200 cells/mm(3), 14 ART recipients with a CD4(+) T-cell count of 50-199 cells/mm(3), and 15 ART-naive adults with a CD4(+) T-cell count of ≥500 cells/mm(3). Subjects received 3 doses of HZ/su (50 µg varicella-zoster virus glycoprotein E [gE] combined with AS01B adjuvant) or 3 doses of saline at months 0, 2, and 6. One month after dose 3, serum anti-gE antibody concentrations and frequencies of gE-specific CD4(+) T cells were higher following HZ/su vaccination than after receipt of saline (P < .0001). Median cell-mediated immune responses peaked after dose 2. Humoral and cell-mediated immune responses persisted until the end of the study (month 18). No vaccination-related serious adverse events were reported. No sustained impact on HIV load or CD4(+) T-cell count was noted following vaccinations. HZ/su was immunogenic and had a clinically acceptable safety profile in HIV-infected adults. NCT01165203. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America.

A cost-benefit analysis of varicella vaccination in Aragón.

PubMed

Peña Blasco, Guillermo; Blasco Pérez-Aramendía, M Jesús

2017-10-01

Varicella, a contagious and infectious disease that is usually benign in children, may become complicated among adults and vulnerable children and may even be life-threatening. There are effective vaccines. A retrospective study was conducted about costs and resulting hospitalizations related to this disease in the population of Aragón in the 2004-2014 period. Costs were compared to the expenses that would have been incurred if those people had received the vaccine and also to the expenses of vaccinating the 1-year-old population over the entire period. A cost-benefit analysis was done to assess the economic impact of varicella vaccination. Data for the 11-year period were provided by the Autonomous Community of Aragón (Spain) and included annual varicella incidence, hospital discharges of varicella cases, costs of primary health care visits and hospitalizations for each year, costs of each workday as per the minimum annual salary and of drugs used). Capitalized costs were estimated and compared to capitalized expenses of vaccination, and a sensitivity analysis was performed. A benefit-cost ratio of 1.6 was obtained considering that all children who had varicella had been vaccinated and had received a booster dose. A benefit-cost ratio of 1.24 was obtained considering that the vaccine had been administered to every 1-year-old individual at a price of EUR 28.59 per vaccine. Over the 11-year period, 53% of hospitalizations corresponded to children younger than 5 years old. Public campaigns for the immunization of children younger than 4 years old with 2 doses lead to cost savings and are cost-effective because the vaccine price results in a benefit-cost ratio greater than 1. A major reduction is expected in the number of hospitalizations among children aged 3-4 years. Sociedad Argentina de Pediatría

[Chickenpox and shingles: one virus, two diseases and current vaccination recommendations in Switzerland].

PubMed

Eckert, Nadine; Masserey Spicher, Virginie

2016-01-01

Adults, pregnant women, premature babies and immunocompromised persons are at increased risk for varicella complications. Therefore the current Swiss vaccination recommendations against varicella include a general recommendation for 11 to 15 year old adolescents with a negative varicella history, as well as a specific recommendation for risk groups. The goal of both recommendations is to reduce varicella complications in persons most at risk. The vaccine is not universally recommended for all toddlers in Switzerland, while this is the case in some countries such as the United States. Pros and cons of different vaccination strategies, as well as possible short- and long-term effects on herpes zoster incidence are taken into account. In the United States, there was a marked decline in incidence and hospitalisations, but an increased herpes zoster incidence in the short term. Finally, public health aspects of herpes zoster, post-herpetic neuralgia and possible vaccination strategies are outlined.

Viral meningitis admitted to an infectious diseases hospital: a retrospective case series.

PubMed

Vâţă, A; Luca, Cătălina M; Duca, Elena; Irina, Teodorescu; Manciuc, Carmen; Vâţă, Luminita G; Dorobăţ, Carmen

2013-01-01

Given its epidemic potential and development of severe forms of disease, viral meningitis (VM) is a serious public health problem. to characterize the main clinical, epidemiologic features, the etiology and treatment of VM cases admitted to the Iasi Infectious Diseases Hospital, in 2012. We retrospectively analyzed the medical records of the patients admitted for viral meningitis at the Iasi "St. Parascheva" Infectious Diseases Hospital in the interval January 1- December 31, 2012 (98 cases). The etiologic diagnosis was made by determining the IgM/IgG antibodies against Coxsackie virus and/or West Nile virus in blood/CSF. There was a fourfold increase in the number of cases as compared to the average for the years 2009-2011. Most cases (73.5%) were children aged 1 to 14 years. 61.8% of patients were males, 51.7% from urban areas. The most common symptom was headache (85.7%), followed by fever (77.6%), and vomiting (66.3%). Neck stiffness was absent in 28.6% cases. In43.5% of the 39 patients serologically investigated a Coxsackie virus infection was confirmed and 1/20 was positive for West Nile virus; three varicella-zoster virus infections and one mumps infection were diagnosed clinically. 68.3% of the patients received first-line antibiotic treatment. The illness mainly affected children, fever and neck stiffness being sometimes absent. The etiology was known in 22.4% of cases; enter viruses being the most frequent causative agent. Most patients received antibiotic therapy. The course was favorable in all cases.

Progressive Outer Retinal Necrosis and Immunosuppressive Therapy in Myasthenia Gravis

PubMed Central

Coisy, Solène; Ebran, Jean-Marc; Milea, Dan

2014-01-01

Introduction Progressive outer retinal necrosis (PORN) is a rare but devastating infectious retinitis associated with varicella zoster virus (VZV) and responsible for severe visual loss. Case Report A 59-year-old man treated for generalized myasthenia with oral azathioprine and prednisone presented with severe unilateral necrotizing retinitis. Polymerase chain reaction of the aqueous and vitreous humors was diagnostic for VZV PORN. Conclusion VZV PORN is a severe potential ocular complication of immunosuppression, prompting urgent diagnosis and appropriate treatment. PMID:24926266

Varicella-Like Cutaneous Toxoplasmosis in a Patient with Aplastic Anemia

PubMed Central

Zimmermann, Stefan; Hadaschik, Eva; Dalpke, Alexander; Hassel, Jessica C.; Ajzenberg, Daniel; Tenner-Racz, Klara; Lehners, Nicola; Kapaun, Annette

2013-01-01

A 60-year-old patient with aplastic anemia presented with vesicular varicella-like skin lesions on her face, arms, legs, back, and abdomen. However, diagnosis for herpetic infection was negative. Findings of a skin biopsy led to a tentative histologic diagnosis of toxoplasmosis, and infection with Toxoplasma gondii was confirmed by immunohistochemistry and PCR. Cutaneous toxoplasmosis is a rare finding in immunocompromised patients and might mimic other infectious diseases, and vesicular lesions associated with toxoplasmosis have not been reported previously. PMID:23390283

Database of Autotransplants for Breast Cancer.

DTIC Science & Technology

1996-12-01

Infections (Indicate code for atypical bacteria; 301 Herpes Simplex (HSV1, HSV2) list bacterium for non-atypical bacteria.) 302 Herpes Zoster ( Chicken pox ...for non-atypical bacteria.) 302 Herpes Zoster ( Chicken pox , Varicella) 303 Cytomegalovirus (CMV) 100 Atypical bacteria, not otherwise specified 304... Chicken pox , Varicella) 303 Cytomegalovirus (CMV) 100 Atypical bacteria, not otherwise specified 304 Adenovirus 101 Coxiella 305 Enterovirus (Coxsackie

Occupational hazards in hospitals: risk of infection.

PubMed Central

Gestal, J J

1987-01-01

In this review of the risk of infection to hospital staff, attention is drawn to the continuing risk presented by hepatitis B and pulmonary tuberculosis, which are more common than diseases such as typhoid fever, brucellosis, histoplasmosis, whooping cough, infectious gastroenteritis, measles, and parotiditis. Other items considered include the susceptibility of female hospital staff to rubella and the importance of their undergoing screening and vaccination; the risks currently presented by epidemic keratoconjunctivitis and by herpes viruses (herpes simplex, varicella zoster, and cytomegalovirus); and the risk of contracting the new infectious diseases (Legionnaires' disease, Marburg disease, Lassa fever, and the acquired immune deficiency syndrome). PMID:3304395

Impact of Underlying Conditions on Zoster-Related Pain and on Quality of Life Following Zoster

PubMed Central

Bricout, Hélène; Bertrand, Isabelle; Perinetti, Emilia; Franco, Elisabetta; Gabutti, Giovanni; Volpi, Antonio

2017-01-01

Abstract Background: Chronic conditions have been investigated as risk factors for developing zoster, but in patients suffering from zoster, the impact of underlying conditions in zoster-related pain and quality of life (QOL) remains unclear. Methods: We performed a post hoc analysis of a prospective cohort study in immunocompetent zoster patients aged 50 years or older, conducted by general practitioners in Italy between 2009 and 2010. Zoster symptoms, pain intensity and characteristics, and physical and mental health scores were assessed at baseline (zoster diagnosis) and at 1, 3, and 6 months of follow-up. Results: Among 413 patients enrolled in the study, 73% (303/413) suffered from underlying conditions of which 69% (209/303) were aged 65 or older. Cardiovascular diseases (75%), diabetes (24%), and respiratory diseases (17%) were most frequent. One to three months after onset, zoster patients with underlying conditions experienced more intense zoster-related pain than those without. QOL scores were significantly lower in patients with underlying conditions, and age-adjusted difference in QOL scores between the groups increased over time, demonstrating a slower recovery for patients with underlying conditions. Conclusions: In addition to age, the main risk factor of zoster occurrence and severity, the presence of underlying conditions results in more painful and impactful zoster episodes, creating a significant burden for these patients. PMID:27793966

Varicella hospitalizations in Los Angeles during the varicella vaccination era, 2003–2011: Are they preventable?

PubMed Central

Agopian, Anya; Lopez, Adriana; Wilson, Dulmini; Peralta, Vi; El Amin, Alvin Nelson; Bialek, Stephanie

2016-01-01

Characteristics of varicella-related hospitalizations in the mature varicella vaccination era, including the proportion vaccinated and the severity of disease, are not well described. We present the vaccination status, severity and reasons for hospitalization of the hospitalized varicella cases reported to the Los Angeles County Health Department from 2003 to 2011, the period which includes the last 4 years of the mature one-dose program and the first 5 years after introduction of the routine two-dose program. A total of 158 hospitalized varicella cases were reported overall, of which 52.5% were potentially preventable and eligible for vaccination, 41.8% were not eligible for vaccination, and 5.7% were vaccinated. Most hospitalizations (72.2%) occurred among healthy persons, 54.4% occurred among persons ≥20 years of age, and 3.8% of hospitalizations resulted in death. Our data suggest that as many as half of the hospitalized varicella cases, including half of the deaths, may have been preventable given that they occurred in persons who were eligible for vaccination. More complete implementation of the routine varicella vaccination program could further reduce the disease burden of severe varicella. PMID:25087675

Cellular and Humoral Responses to a Second Dose of Herpes Zoster Vaccine Administered 10 Years After the First Dose Among Older Adults.

PubMed

Levin, Myron J; Schmader, Kenneth E; Pang, Lei; Williams-Diaz, Angela; Zerbe, Gary; Canniff, Jennifer; Johnson, Michael J; Caldas, Yupanqui; Cho, Alice; Lang, Nancy; Su, Shu-Chih; Parrino, Janie; Popmihajlov, Zoran; Weinberg, Adriana

2016-01-01

Herpes zoster vaccine (ZV) was administered as a second dose to 200 participants ≥ 70 years old who had received a dose of ZV ≥ 10 years previously (NCT01245751). Varicella zoster virus (VZV) antibody titers (measured by a VZV glycoprotein-based enzyme-linked immunosorbent assay [gpELISA]) and levels of interferon γ (IFN-γ) and interleukin 2 (IL-2; markers of VZV-specific cell-mediated immunity [CMI], measured by means of ELISPOT analysis) in individuals aged ≥ 70 years who received a booster dose of ZV were compared to responses of 100 participants aged 50-59 years, 100 aged 60-69 years, and 200 aged ≥ 70 years who received their first dose of ZV. The study was powered to demonstrate noninferiority of the VZV antibody response at 6 weeks in the booster-dose group, compared with the age-matched first-dose group. Antibody responses were similar at baseline and after vaccination across all age and treatment groups. Both baseline and postvaccination VZV-specific CMI were lower in the older age groups. Peak gpELISA titers and their fold rise from baseline generally correlated with higher baseline and postvaccination VZV-specific CMI. IFN-γ and IL-2 results for subjects ≥ 70 years old were significantly higher at baseline and after vaccination in the booster-dose group, compared with the first-dose group, indicating that a residual effect of ZV on VZV-specific CMI persisted for ≥ 10 years and was enhanced by the booster dose. These findings support further investigation of ZV administration in early versus later age and of booster doses for elderly individuals at an appropriate interval after initial immunization against HZ. NCT01245751. © The Author 2015. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience

PubMed Central

Willis, English D.; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W.; Halsey, Neal A.; Gershon, Anne A.

2017-01-01

Background Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. Methods All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. Results A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. Conclusions The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. PMID:29174682

Zoster Vaccine and the Risk of Postherpetic Neuralgia in Patients Who Developed Herpes Zoster Despite Having Received the Zoster Vaccine.

PubMed

Tseng, Hung Fu; Lewin, Bruno; Hales, Craig M; Sy, Lina S; Harpaz, Rafael; Bialek, Stephanie; Luo, Yi; Jacobsen, Steven J; Reddy, Kavya; Huang, Po-Yin; Zhang, Jeff; Anand, Sean; Bauer, Erin Mary; Chang, Jennifer; Tartof, Sara Y

2015-10-15

Although it is evident that zoster vaccination reduces postherpetic neuralgia (PHN) risk by reducing herpes zoster (HZ) occurrence, it is less clear whether the vaccine protects against PHN among patients who develop HZ despite previous vaccination. This cohort study included immunocompetent patients with HZ. The vaccinated cohort included 1155 individuals who were vaccinated against HZ at age ≥60 years and had an HZ episode after vaccination. Vaccinated patients were matched 1:1 by sex and age with unvaccinated patients. Trained medical residents reviewed the full medical record to determine the presence of HZ-related pain at 1, 2, 3, and 6 months after HZ diagnosis. The incidence of PHN was compared between vaccinated and unvaccinated -patients. Thirty vaccinated women (4.2%) experienced PHN, compared with 75 unvaccinated women (10.4%), with an adjusted relative risk of 0.41 (95% confidence interval, .26-.64). PHN occurred in 26 vaccinated men (6.0%) versus 25 unvaccinated men (5.8%), with an adjusted relative risk of 1.06 (.58-1.94). These associations did not differ significantly by age. Among persons experiencing HZ, prior HZ vaccination is associated with a lower risk of PHN in women but not in men. This sex-related difference may reflect differences in healthcare-seeking patterns and deserve further investigation. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Herpes zoster vaccine: A health economic evaluation for Switzerland.

PubMed

Blank, Patricia R; Ademi, Zanfina; Lu, Xiaoyan; Szucs, Thomas D; Schwenkglenks, Matthias

2017-07-03

Herpes zoster (HZ) or "shingles" results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65-79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65-79 y.

Shingles (Herpes Zoster)

MedlinePlus

... Form Controls Cancel Submit Search The CDC Shingles (Herpes Zoster) Note: Javascript is disabled or is not ... United States will develop shingles, also known as herpes zoster, in their lifetime. There are an estimated ...

Herpes Zoster Meningitis Presenting With a Cerebrospinal Fluid Leukemoid Reaction in an Adolescent With preB-ALL in Remission.

PubMed

Adachi, Kristina; Song, Sophie X; Kao, Roy L; Van Dyne, Elizabeth; Kempert, Pamela; Deville, Jaime G

2016-08-01

A 19-year-old girl with a history of precursor B acute lymphoblastic leukemia in remission presented with fever, headache, and a skin rash. Cerebrospinal fluid (CSF) examination reported pleocytosis with blast-like cells concerning for a central nervous system leukemic relapse. After the patient showed significant improvement on intravenous acyclovir, a repeat lumbar puncture revealed normalization of CSF. The abnormal CSF cells were reviewed and ultimately determined to be activated and atypical lymphocytes. The patient recovered uneventfully. Atypical lymphocytes resembling leukemic blasts are an unusual finding in viral meningitis. Varicella zoster virus reactivation should be considered during initial evaluation for central nervous system relapse of leukemia.

Vaccination against zoster remains effective in older adults who later undergo chemotherapy.

PubMed

Tseng, Hung Fu; Tartof, Sara; Harpaz, Rafael; Luo, Yi; Sy, Lina S; Hetcher, Rulin C; Jacobsen, Steven J

2014-10-01

Approximately 40% of adults develop invasive cancer during their lifetimes, many of whom require chemotherapy. Herpes zoster (HZ) is common and often severe in patients undergoing chemotherapy, yet there are no data regarding whether these patients retain specific protection against HZ if they had previously received zoster vaccine. We conducted a study to determine whether zoster vaccine was effective in patients who subsequently underwent chemotherapy. The cohort study consisted of Kaiser Permanente Southern California members aged ≥60 years treated with chemotherapy. The exposure variable was receipt of zoster vaccine prior to initiation of chemotherapy. Incident HZ cases were identified using International Classification of Diseases, Ninth Revision diagnostic codes. HZ incidence rates were calculated; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression models. There were 91 and 583 HZ cases in the vaccinated and unvaccinated cohorts, respectively, yielding an incidence rate of 12.87 (95% CI, 10.48-15.80) vs 22.05 (95% CI, 20.33-23.92) per 1000 person-years. Thirty-month cumulative incidence was 3.28% in the vaccinated group and 5.34% in the unvaccinated group (P < .05). The adjusted HR for HZ was 0.58 (95% CI, .46-.73) and showed no significant variation by age, sex, or race. HZ incidence rates remained increased in the small subgroup of persons receiving zoster vaccine within 60 days before chemotherapy, but this was the only group affected by indication bias. No vaccinated patients underwent hospitalization for HZ, compared with 6 unvaccinated patients. Zoster vaccine continues to protect against HZ if recipients later undergo chemotherapy. Our findings provide an additional rationale for offering zoster vaccine to indicated adults while they are immunocompetent. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved

Cytomegalovirus seropositivity is associated with herpes zoster

PubMed Central

Ogunjimi, Benson; Hens, Niel; Pebody, Richard; Jansens, Hilde; Seale, Holly; Quinlivan, Mark; Theeten, Heidi; Goossens, Herman; Breuer, Judy; Beutels, Philippe

2015-01-01

Herpes zoster (HZ) is caused by VZV reactivation that is facilitated by a declined immunity against varicella-zoster virus (VZV), but also occurs in immunocompetent individuals. Cytomegalovirus (CMV) infection is associated with immunosenescence meaning that VZV-specific T-cells could be less responsive. This study aimed to determine whether CMV infection could be a risk factor for the development of HZ. CMV IgG serostatus was determined in stored serum samples from previously prospectively recruited ambulatory adult HZ patients in the UK (N = 223) in order to compare the results with those from UK population samples (N = 1545) by means of a logistic regression (controlling for age and gender). Furthermore, we compared the UK population CMV seroprevalence with those from population samples from other countries (from Belgium (N1 = 1741, N2 = 576), USA (N = 5572) and Australia (N = 2080)). Furthermore, CMV IgG titers could be compared between UK HZ patients and Belgium N2 population samples because the same experimental set-up for analysis was used. We found UK ambulatory HZ patients to have a higher CMV seroprevalence than UK population samples (OR 1.56 [1.11 2.19]). CMV IgG seropositivity was a significant risk factor for HZ in the UK (OR 3.06 [1.32 7.04]. Furthermore, high CMV IgG titers (exceeding the upper threshold) were less abundant in CMV-seropositive Belgian N2 population samples than in CMV-seropositive UK HZ patients (OR 0.51 [0.31 0.82]. We found CMV-seroprevalence to increase faster with age in the UK than in other countries (P < 0.05). We conclude that CMV IgG seropositivity is associated with HZ. This finding could add to the growing list of risk factors for HZ. PMID:25905443

Comparison of two strategies to prevent varicella outbreaks in housing facilities for asylum seekers.

PubMed

de Valliere, Serge; Cani, Naim; Grossenbacher, Maya; Puig, Francisco; Masserey, Eric; Bodenmann, Patrick

2011-10-01

The proportion of adults with positive varicella serology is lower in populations from tropical countries. Therefore immigrants to countries with a temperate climate are at risk of acquiring varicella infection during adulthood. We tested two different strategies to prevent varicella outbreaks in housing facilities for asylum seekers arriving in the Canton of Vaud, Switzerland. The first strategy consisted of a rapid response with isolation of the affected individuals and vaccination of the susceptible contacts. The second strategy consisted of a general vaccination upon arrival of all asylum seekers aged 15-39 years with no history of chickenpox. From May 2008 to January 2009 we applied the rapid response strategy. Eight hundred and fifty-eight asylum seekers arrived in the Canton and an attack rate of 2.8% (seven cases among 248 exposed asylum seekers) was observed. The mean cost was US$ 31.35 per asylum seeker. The general vaccination strategy was applied from February 2009 to May 2010, a period during which 966 asylum seekers were registered. This second strategy completely prevented any outbreak at a mean cost of US$ 83.85 per asylum seeker. Of the two analyzed interventions to prevent varicella outbreaks in housing facilities for asylum seekers, the general vaccination strategy was more effective, more sustainable, and ethically preferable, although more costly. Copyright © 2011 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Varicella infection is not associated with increasing prevalence of eczema: a U.S. population-based study.

PubMed

Li, J C; Silverberg, J I

2015-11-01

Chickenpox infection early in childhood has previously been shown to protect against the development of childhood eczema in line with the hygiene hypothesis. In 1995, the American Academy of Pediatrics recommended routine vaccination against varicella zoster virus in the United States. Subsequently, rates of chickenpox infection have dramatically decreased in childhood. We sought to understand the impact of declining rates of chickenpox infection on the prevalence of eczema. We analysed data from 207 007 children in the 1997-2013 National Health Interview Survey. One-year prevalence of eczema and 'ever had' history of chickenpox were analysed. Associations between chickenpox infection and eczema were tested using survey-weighted logistic regression. The impact of chickenpox on trends of eczema prevalence was tested using survey logistic regression and generalized linear models. Children with a history of chickenpox compared with those without chickenpox had a lower prevalence [survey-weighted logistic regression (95% confidence interval, CI)] of eczema [8·8% (8·5-9·0%) vs. 10·6% (10·4-10·8%)]. In pooled multivariate models controlling for age, sex, race/ethnicity, household income, highest level of household education, insurance coverage, U.S. birthplace and family size, eczema was inversely associated with chickenpox [adjusted odds ratio (95% CI), 0·90 (0·86-0·94), P < 0·001]. The prevalence of eczema significantly increased over time (Tukey post-hoc test, P < 0·001 for comparisons of survey years 2001-13 vs. 1997-2000, 2008-13 vs. 2001-04 and 2008-13 vs. 2005-07). In multivariate generalized linear models, the odds of eczema was not associated with chickenpox in 2001-13 (P ≥ 0·06). These findings suggest that lower rates of chickenpox infection secondary to widespread vaccination against varicella zoster virus are not contributing to higher rates of childhood eczema in the U.S. © 2015 British Association of Dermatologists.

Human parvovirus B19, varicella zoster virus, and human herpesvirus-6 in mesenchymal stem cells of patients with osteoarthritis: analysis with quantitative real-time polymerase chain reaction.

PubMed

Rollín, R; Alvarez-Lafuente, R; Marco, F; Jover, J A; Hernández-García, C; Rodríguez-Navas, C; López-Durán, L; Fernández-Gutiérrez, B

2007-04-01

To investigate whether there is a possible viral transmission using mesenchymal stem cells (MSCs) in autologous or allogeneic transplantation in the context of osteoarthritis (OA) patients. The presence of parvovirus B19 (B19), varicella zoster virus (VZV), and human herpesvirus-6 (HHV-6) was studied in MSCs from bone marrow of patients with OA and healthy controls. MSCs were prepared from bone marrow aspirates obtained from 18 patients undergoing joint replacement as a result of OA and from 10 healthy controls. DNA was extracted from primary MSCs' culture established from these cells and quantitative real-time polymerase chain reaction was performed to analyse the prevalence and viral load of B19, VZV and HHV-6. The prevalence of total viral DNA among patients with OA was 16.7% (3/18), with a mean viral load of 29.7 copies/microg of DNA. One out of 18 was positive for B19 (viral load, 61.2 copies/microg of DNA), two for VZV (mean viral load, 14.4 copies/microg of DNA), and none for HHV-6. The prevalence of total viral DNA in the control group was 20% (2/10), with a mean viral load of 13.4 copies/microg of DNA. Both positive results were of B19 parvoviruses. There were no statistically significant differences among patients and controls. This first approach to the viral prevalence in MSCs of bone marrow in OA patients and healthy controls seems to show a very low risk of viral transmission or reactivation in a possible MSCs' transplantation.

Selection and Characterization of Drug-Resistant Variants of Human Immunodeficiency Virus (AIDS).

DTIC Science & Technology

1995-10-01

on Antiviral Reserach, Santa Fe, New Mexico , 1995. Page 18 APPENDIX Page 19 p - FACTFILE Mutations in HIV-1 Reverse Transcriptase and Protease...including herpes simplex viruses, varicella -zoster Resistance of clinical HIV-1 isolates to foscarnet has not virus, cytomegalovirus (CMV), hepatitis B...This effect of the Tyr-208 substitution was not ob- reported previously for herpes simplex viruses, varicella -zoster served in MT-2 cells, however. virus

Pathogenesis of varicelloviruses in primates.

PubMed

Ouwendijk, Werner J D; Verjans, Georges M G M

2015-01-01

Varicelloviruses in primates comprise the prototypic human varicella-zoster virus (VZV) and its non-human primate homologue, simian varicella virus (SVV). Both viruses cause varicella as a primary infection, establish latency in ganglionic neurons and reactivate later in life to cause herpes zoster in their respective hosts. VZV is endemic worldwide and, although varicella is usually a benign disease in childhood, VZV reactivation is a significant cause of neurological disease in the elderly and in immunocompromised individuals. The pathogenesis of VZV infection remains ill-defined, mostly due to the species restriction of VZV that impedes studies in experimental animal models. SVV infection of non-human primates parallels virological, clinical, pathological and immunological features of human VZV infection, thereby providing an excellent model to study the pathogenesis of varicella and herpes zoster in its natural host. In this review, we discuss recent studies that provided novel insight in both the virus and host factors involved in the three elementary stages of Varicellovirus infection in primates: primary infection, latency and reactivation. Copyright © 2014 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Association between vaccination for herpes zoster and risk of herpes zoster infection among older patients with selected immune-mediated diseases.

PubMed

Zhang, Jie; Xie, Fenglong; Delzell, Elizabeth; Chen, Lang; Winthrop, Kevin L; Lewis, James D; Saag, Kenneth G; Baddley, John W; Curtis, Jeffrey R

2012-07-04

Based on limited data, the live attenuated herpes zoster (HZ) vaccine is contraindicated in patients taking anti-tumor necrosis factor (anti-TNF) therapies or other biologics commonly used to treat immune-mediated diseases. The safety and effectiveness of the vaccine are unclear for these patients. To examine the association between HZ vaccination and HZ incidence within and beyond 42 days after vaccination in patients with selected immune-mediated diseases and in relation to biologics and other therapies used to treat these conditions. Retrospective cohort study of 463,541 Medicare beneficiaries 60 years and older with rheumatoid arthritis, psoriasis, psoriatic arthritis, ankylosing spondylitis, or inflammatory bowel disease using Medicare claims data from January 1, 2006, through December 31, 2009. Herpes zoster incidence rate within 42 days after vaccination (a safety concern) and beyond 42 days; hazard ratios estimated using Cox proportional hazards models for HZ comparing vaccinated vs unvaccinated patients. Median duration of follow-up was 2.0 years (interquartile range, 0.8-3.0); 4.0% of patients received HZ vaccine. The overall crude HZ incidence rate was 7.8 cases per 1000 person-years (95% CI, 3.7-16.5) within 42 days after vaccination. The rate among the unvaccinated was 11.6 cases per 1000 person-years (95% CI, 11.4-11.9). Among 633 patients exposed to biologics at the time of vaccination or within the subsequent 42 days, no case of HZ or varicella occurred. After multivariable adjustment, HZ vaccination was associated with a hazard ratio of 0.61 (95% CI, 0.52-0.71) for HZ risk after 42 days. Receipt of HZ vaccine was not associated with a short-term increase in HZ incidence among Medicare beneficiaries with selected immune-mediated diseases, including those exposed to biologics. The vaccine was associated with a lower HZ incidence over a median of 2 years of follow-up.

Increasing Incidence of Herpes Zoster Over a 60-year Period From a Population-based Study

PubMed Central

Kawai, Kosuke; Yawn, Barbara P.; Wollan, Peter; Harpaz, Rafael

2016-01-01

Background. Temporal increases in the incidence of herpes zoster (HZ) have been reported but studies have examined short study periods, and the cause of the increase remains unknown. We examined the long-term trend of HZ. Methods. A population-based cohort study was conducted in Olmsted County, Minnesota, using data from 1945–1960 and 1980–2007. Medical records review of possible cases was performed to confirm incident cases of HZ, the patient's immune status, and prescribing of antivirals for HZ. We examined the relative change in the temporal trend in the incidence rates before and after the introduction of the varicella vaccination program. Results. Of the 8017 patients with HZ, 58.7% were females and 6.6% were immunocompromised. The age- and sex-adjusted incidence rate of HZ increased from 0.76 per 1000 person-years (PY) (95% confidence interval [CI], .63–.89) in 1945–1949 to 3.15 per 1000 PY (95% CI, 3.04–3.26) in 2000–2007. The rate of increase across the time period was 2.5% per year after adjusting for age and sex (adjusted incidence rate ratio, 1.025 [95% CI, 1.023–1.026]; P < .001). The incidence of HZ significantly increased among all age groups and both sexes. We found no change in the rate of increase before vs after the introduction of the varicella vaccination program. Conclusions. The incidence of HZ has increased >4-fold over the last 6 decades. This increase is unlikely to be due to the introduction of varicella vaccination, antiviral therapy, or change in the prevalence of immunocompromised individuals. PMID:27161774

Chicken pox outbreak in the Intensive Care Unit of a tertiary care hospital: Lessons learnt the hard way.

PubMed

Sarit, Sharma; Shruti, Sharma; Deepinder, Chhina; Chhina, R S

2015-12-01

Varicella-zoster virus (VZV) causes 2 clinically and epidemiologically distinct forms of diseases. Chickenpox (varicella) is the disease that results from primary infection with the VZV. Herpes zoster (HZ) results from the reactivation of VZV latently infecting the dorsal root ganglia. We are reporting an outbreak of varicella infection among the health care workers (HCWs) in the Intensive Care Unit (ICU) of a tertiary care hospital. We found transmission of varicella among eight HCWs of pulmonary ICU. They had a history of contact with a patient having HZ infection. Investigation of the outbreak was conducted as per guidelines. Better dissemination of information on disease transmission, isolation of infected patients inside the hospital, and adequate protection (including vaccination) for susceptible employees are important to prevent such outbreaks.

Herpes zoster vaccine: A health economic evaluation for Switzerland

PubMed Central

Blank, Patricia R.; Ademi, Zanfina; Lu, Xiaoyan; Szucs, Thomas D.; Schwenkglenks, Matthias

2017-01-01

ABSTRACT Herpes zoster (HZ) or “shingles” results from a reactivation of the varicella zoster virus (VZV) acquired during primary infection (chickenpox) and surviving in the dorsal root ganglia. In about 20% of cases, a complication occurs, known as post-herpetic neuralgia (PHN). A live attenuated vaccine against VZV is available for the prevention of HZ and subsequent PHN. The present study aims to update an earlier evaluation estimating the cost-effectiveness of the HZ vaccine from a Swiss third party payer perspective. It takes into account updated vaccine prices, a different age cohort, latest clinical data and burden of illness data. A Markov model was developed to simulate the lifetime consequences of vaccinating 15% of the Swiss population aged 65–79 y. Information from sentinel data, official statistics and published literature were used. Endpoints assessed were number of HZ and PHN cases, quality-adjusted life years (QALYs), costs of hospitalizations, consultations and prescriptions. Based on a vaccine price of CHF 162, the vaccination strategy accrued additional costs of CHF 17,720,087 and gained 594 QALYs. The incremental cost-effectiveness ratio (ICER) was CHF 29,814 per QALY gained. Sensitivity analyses showed that the results were most sensitive to epidemiological inputs, utility values, discount rates, duration of vaccine efficacy, and vaccine price. Probabilistic sensitivity analyses indicated a more than 99% chance that the ICER was below 40,000 CHF per QALY. Findings were in line with existing cost-effectiveness analyses of HZ vaccination. This updated study supports the value of an HZ vaccination strategy targeting the Swiss population aged 65–79 y. PMID:28481678

Herpes zoster following cryosurgery.

PubMed

Lee, Michael R; Ryman, William

2005-02-01

A 56-year-old man developed reactivation of herpes zoster infection on his right forehead after treatment of several solar keratoses with cryosurgery. The rash was blistering and painful. Treatment with oral aciclovir was instituted and the lesions healed within 2 weeks. Known risk factors for reactivation include age and decreased immunity. Previous case reports have indicated trauma may be a risk factor in herpes zoster. We report a case of herpes zoster as a complication of cryosurgery.

Guillain-Barré syndrome following chickenpox: a case series.

PubMed

Tatarelli, P; Garnero, M; Del Bono, V; Camera, M; Schenone, A; Grandis, M; Benedetti, L; Viscoli, C

2016-01-01

Guillain-Barré syndrome (GBS) is an acute, immune-mediated polyradiculoneuropathy, usually triggered by an infectious episode, mostly of viral origin. Varicella zoster virus (VZV) is a rare cause of GBS, mainly in the case of latent infection reactivation. We report on three adult patients who developed GBS following chickenpox, after a short period of latency. They were promptly treated with intravenous immunoglobulin, and the first one with plasma exchange additionally. All the patients experienced almost complete clinical recovery. Our experience suggests that primary VZV infection constitutes a GBS triggering event.

Does herpes zoster predispose to giant cell arteritis: a geo-epidemiologic study.

PubMed

Ing, Edsel B; Ing, Royce; Liu, Xinyang; Zhang, Angela; Torun, Nurhan; Sey, Michael; Pagnoux, Christian

2018-01-01

Giant cell arteritis (GCA) is the most common systemic vasculitis in the elderly and can cause irreversible blindness and aortitis. Varicella zoster (VZ), which is potentially preventable by vaccination, has been proposed as a possible immune trigger for GCA, but this is controversial. The incidence of GCA varies widely by country. If VZ virus contributes to the immunopathogenesis of GCA we hypothesized that nations with increased incidence of GCA would also have increased incidence of herpes zoster (HZ). We conducted an ecologic analysis to determine the relationship between the incidence of HZ and GCA in different countries. A literature search for the incidence rates (IRs) of GCA and HZ from different countries was conducted. Correlation and linear regression was performed comparing the disease IR of each country for subjects 50 years of age or older. We found the IR for GCA and HZ from 14 countries. Comparing the IRs for GCA and HZ in 50-year-olds, the Pearson product-moment correlation ( r ) was -0.51, with linear regression coefficient (β) -2.92 (95% CI -5.41, -0.43; p =0.025) using robust standard errors. Comparing the IRs for GCA and HZ in 70-year-olds, r was -0.40, with β -1.78, which was not statistically significant (95% CI -4.10, 0.53; p =0.12). Although this geo-epidemiologic study has potential for aggregation and selection biases, there was no positive biologic gradient between the incidence of clinically evident HZ and GCA.

Immune Responses to a Recombinant Glycoprotein E Herpes Zoster Vaccine in Adults Aged 50 Years or Older

PubMed Central

Cunningham, Anthony L; Heineman, Thomas C; Lal, Himal; Godeaux, Olivier; Chlibek, Roman; Hwang, Shinn-Jang; McElhaney, Janet E; Vesikari, Timo; Andrews, Charles; Choi, Won Suk; Esen, Meral; Ikematsu, Hideyuki; Choma, Martina Kovac; Pauksens, Karlis; Ravault, Stéphanie; Salaun, Bruno; Schwarz, Tino F; Smetana, Jan; Abeele, Carline Vanden; Van den Steen, Peter; Vastiau, Ilse; Weckx, Lily Yin; Levin, Myron J

2018-01-01

Abstract Background The herpes zoster subunit vaccine (HZ/su), consisting of varicella-zoster virus glycoprotein E (gE) and AS01B Adjuvant System, was highly efficacious in preventing herpes zoster in the ZOE-50 and ZOE-70 trials. We present immunogenicity results from those trials. Methods Participants (ZOE-50: ≥50; ZOE-70: ≥70 years of age) received 2 doses of HZ/su or placebo, 2 months apart. Serum anti-gE antibodies and CD4 T cells expressing ≥2 of 4 activation markers assessed (CD42+) after stimulation with gE-peptides were measured in subcohorts for humoral (n = 3293) and cell-mediated (n = 466) immunogenicity. Results After vaccination, 97.8% of HZ/su and 2.0% of placebo recipients showed a humoral response. Geometric mean anti-gE antibody concentrations increased 39.1-fold and 8.3-fold over baseline in HZ/su recipients at 1 and 36 months post-dose 2, respectively. A gE-specific CD42+ T-cell response was shown in 93.3% of HZ/su and 0% of placebo recipients. Median CD42+ T-cell frequencies increased 24.6-fold (1 month) and 7.9-fold (36 months) over baseline in HZ/su recipients and remained ≥5.6-fold above baseline in all age groups at 36 months. The proportion of CD4 T cells expressing all 4 activation markers increased over time in all age groups. Conclusions Most HZ/su recipients developed robust immune responses persisting for 3 years following vaccination. Clinical Trials Registration NCT01165177; NCT01165229. PMID:29529222

Shingles (Herpes Zoster) Vaccine (Zostavax(®)): A Review in the Prevention of Herpes Zoster and Postherpetic Neuralgia.

PubMed

Keating, Gillian M

2016-06-01

Zostavax(®) is a live attenuated shingles (herpes zoster) vaccine approved in the EU for the prevention of herpes zoster (HZ) and postherpetic neuralgia (PHN) in adults aged ≥50 years. Zoster vaccine protected against HZ in adults aged 50-59 years (ZEST trial) and ≥60 years [Shingles Prevention Study (SPS)], and also reduced the burden of illness associated with HZ and the risk of PHN in adults aged ≥60 years (SPS). A large amount of real-world data also supports the efficacy of zoster vaccine. Results of the SPS Short- and Long-Term Persistence Substudies and real-world studies indicate that zoster vaccine provided continued benefit in the longer term, albeit with a gradual decline in vaccine efficacy over time; long-term effectiveness studies are ongoing. The need for a booster dose is still unknown, but a study showed that, if necessary, a booster dose administered to adults aged ≥70 years who received their first dose of zoster vaccine ≥10 years previously was immunogenic. Zoster vaccine had a favourable safety and tolerability profile, with the most commonly reported adverse events being non-severe injection-site reactions. In conclusion, zoster vaccine reduces the incidence of HZ and PHN, thereby reducing the burden of illness associated with HZ; improved uptake of zoster vaccine is needed.

The Etiology of Intraocular Inflammation in HIV Positive and HIV Negative Adults at a Tertiary Hospital in Cape Town, South Africa.

PubMed

Smit, Derrick P; Esterhuizen, Tonya M; Meyer, David; de Boer, Joke H; de Groot-Mijnes, Jolanda D F

2018-05-30

To describe the patterns of uveitis in South Africa. Prospective cross-sectional study. One hundred and six patients were enrolled and 37.7% had human immune-deficiency virus (HIV) infection. Anterior and panuveitis occurred most frequently. Infectious, non-infectious and idiopathic uveitis were diagnosed in 66.0%, 17.0% and 17.0% of all cases, respectively. Eighty percent of HIV+ cases had infectious uveitis. Overall, intraocular tuberculosis (IOTB), herpetic and syphilitic uveitis were the commonest infectious causes. Sarcoidosis and HLA-B27-associated uveitis were the commonest non-infectious causes. In anterior uveitis, HIV+ cases most frequently had probable IOTB, syphilitic or idiopathic uveitis while HIV- cases had possible IOTB, idiopathic or HLA-B27-associated uveitis. In panuveitis, HIV+ cases mostly had syphilis, probable IOTB, toxoplasma and varicella-zoster virus whereas HIV- cases mostly had possible IOTB, sarcoidosis and idiopathic uveitis. Infectious uveitis is common in South Africa, especially amongst HIV+ patients. Causes of anterior and panuveitis differ between HIV+ and HIV- patients.

Herpes zoster vaccine live: A 10 year review of post-marketing safety experience.

PubMed

Willis, English D; Woodward, Meredith; Brown, Elizabeth; Popmihajlov, Zoran; Saddier, Patricia; Annunziato, Paula W; Halsey, Neal A; Gershon, Anne A

2017-12-19

Zoster vaccine is a single dose live, attenuated vaccine (ZVL) indicated for individuals ≥50 years-old for the prevention of herpes zoster (HZ). Safety data from clinical trials and post-licensure studies provided reassurance that ZVL is generally safe and well tolerated. The objective of this review was to provide worldwide post-marketing safety information following 10 years of use and >34 million doses distributed. All post-marketing adverse experience (AE) reports received worldwide between 02-May-2006 and 01-May-2016 from healthcare professionals following vaccination with ZVL and submitted to the MSD AE global safety database, were analyzed. A total of 23,556 AE reports, 93% non-serious, were reported. Local injection site reactions (ISRs), with a median time-to-onset of 2 days, were the most frequently reported AEs followed by HZ. The majority of HZ reports were reported within 2 weeks of vaccination and considered, based on time-to-onset, pathogenesis of HZ, and data from clinical trials, to be caused by wild-type varicella-zoster virus (VZV). HZ confirmed by PCR analysis to be VZV Oka/Merck vaccine-strain was identified in an immunocompetent individual 8 months postvaccination and in 4 immunocompromised individuals. Disseminated HZ was reported very rarely (<1%) with 38% occurring in immunocompromised individuals. All reports of disseminated HZ confirmed by PCR as VZV Oka/Merck vaccine-strain were in individuals with immunosuppressive conditions and/or therapy at the time of vaccination. The safety profile of ZVL, following 10 years of post-marketing use, was favorable and consistent with that observed in clinical trials and post-licensure studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Increased seroprevalence of IgG-class antibodies against cytomegalovirus, parvovirus B19, and varicella-zoster virus in women working in child day care

PubMed Central

2012-01-01

Background Primary maternal infection with cytomegalovirus (CMV), parvovirus B19 (B19V), and varicella-zoster virus (VZV) may result in adverse pregnancy outcomes like congenital infection or foetal loss. Women working in child day care have an increased exposure to CMV, B19V, and VZV. By comparing the seroprevalence of IgG-class antibodies against CMV, VZV and B19V in female day care workers (DCW) with the seroprevalence in women not working in day care this study aimed to assess the association between occupation and infection. Methods A cross-sectional design was used. Out of a random sample of 266 day care centres, demographic data, data on work history, and blood samples were collected from 285 women from 38 centres. In addition, blood samples and basic demographics from women who participated in a cross-sectional survey of the Amsterdam population (2004) were used. All blood samples were tested for IgG-class antibodies against CMV, B19V, and VZV. Results Twenty-seven percent of the DCW were still susceptible to B19V or CMV. Working in day care was independently associated with B19V infection in all DCW (prevalence ratio [PR] 1.2; 95 % CI 1.1–1.3), and with CMV infection in DCW of European origin only (PR 1.7; 95 % CI 1.3–2.3). Almost all women born outside Europe tested seropositive for CMV (96 %). All DCW tested seropositive for VZV, compared to only 94 % of the women not working in day care. Conclusion This study confirms the clear association between employment in child day care centres and infection with CMV and B19V. Intervention policies, like screening of new employees and awareness campaigns emphasizing hygienic measures among DCW, should be implemented urgently to improve the maternal health of these women and the health of their offspring. PMID:22726391

Chickenpox (image)

MedlinePlus

Chickenpox is caused by the varicella-zoster virus, a member of the herpesvirus family. The same virus also causes herpes zoster, shingles, in adults. Chickenpox is extremely contagious, and can be spread by ...

Herpes zoster vaccine and the incidence of recurrent herpes zoster in an immunocompetent elderly population.

PubMed

Tseng, Hung Fu; Chi, Margaret; Smith, Ning; Marcy, Stephen M; Sy, Lina S; Jacobsen, Steven J

2012-07-15

The benefit of vaccinating immunocompetent patients who have had shingles has not been examined. The study assessed the association between vaccination and the incidence of herpes zoster recurrence among persons with a recent episode of clinically diagnosed herpes zoster. This is a matched cohort study in Kaiser Permanente Southern California. Study populations were immunocompetent elderly individuals ≥ 60 years old with a recent episode of herpes zoster. Incidence of recurrent herpes zoster was compared between the vaccinated and the unvaccinated matched cohorts. A total of 1036 vaccinated and 5180 unvaccinated members were included. On the basis of clinically confirmed cases, the incidence of recurrent herpes zoster among persons aged <70 years was 0.99 (95% confidence interval [CI], .02-5.54) and 2.20 (95% CI, 1.10-3.93) cases per 1000 person-years in the vaccinated and unvaccinated cohorts, respectively. The adjusted hazard ratio was 0.39 (95% CI, .05-4.45) among persons aged <70 years and 1.05 (95% CI, .30-3.69) among persons aged ≥ 70 years. The risk of herpes zoster recurrence following a recent initial episode is fairly low among immunocompetent adults, regardless of vaccination status. Such a low risk suggests that one should evaluate the necessity of immediately vaccinating immunocompetent patients who had a recent herpes zoster episode.

Family Characteristics Associated with Likelihood of Varicella Vaccination.

PubMed

Weinmann, Sheila; Mullooly, John P; Drew, Lois; Chun, Colleen S

2016-01-01

The introduction of the varicella vaccine as a routine pediatric immunization in the US, in 1995, provided an opportunity to assess factors associated with uptake of new vaccines in the member population of the Kaiser Permanente Northwest (KPNW) Health Plan. Identify factors associated with varicella vaccination in the KPNW population in the first five years after varicella vaccine was introduced. A retrospective cohort of children under age 13 years between June 1995 and December 1999, without a history of varicella disease was identified using KPNW automated data. Membership records were linked to vaccine databases. Cox regression was used to estimate likelihood of varicella vaccination during the study period in relation to age, sex, primary clinician's specialty, and Medicaid eligibility. For a subset whose parents answered a behavioral health survey, additional demographic and behavioral characteristics were evaluated. Varicella vaccination. We identified 88,646 children under age 13 years without a history of varicella; 22% were vaccinated during the study period. Varicella vaccination was more likely among children who were born after 1995, were not Medicaid recipients, or had pediatricians as primary clinicians. In the survey-linked cohort, positively associated family characteristics included smaller family size; higher socioeconomic status; and parents who were older, were college graduates, reported excellent health, and received influenza vaccination. Understanding predictors of early varicella vaccine-era vaccine acceptance may help in planning for introduction of new vaccines to routine schedules.

Family Characteristics Associated with Likelihood of Varicella Vaccination

PubMed Central

Weinmann, Sheila; Mullooly, John P; Drew, Lois; Chun, Colleen S

2016-01-01

Context: The introduction of the varicella vaccine as a routine pediatric immunization in the US, in 1995, provided an opportunity to assess factors associated with uptake of new vaccines in the member population of the Kaiser Permanente Northwest (KPNW) Health Plan. Objective: Identify factors associated with varicella vaccination in the KPNW population in the first five years after varicella vaccine was introduced. Design: A retrospective cohort of children under age 13 years between June 1995 and December 1999, without a history of varicella disease was identified using KPNW automated data. Membership records were linked to vaccine databases. Cox regression was used to estimate likelihood of varicella vaccination during the study period in relation to age, sex, primary clinician’s specialty, and Medicaid eligibility. For a subset whose parents answered a behavioral health survey, additional demographic and behavioral characteristics were evaluated. Main Outcome Measure: Varicella vaccination. Results: We identified 88,646 children under age 13 years without a history of varicella; 22% were vaccinated during the study period. Varicella vaccination was more likely among children who were born after 1995, were not Medicaid recipients, or had pediatricians as primary clinicians. In the survey-linked cohort, positively associated family characteristics included smaller family size; higher socioeconomic status; and parents who were older, were college graduates, reported excellent health, and received influenza vaccination. Conclusion: Understanding predictors of early varicella vaccine-era vaccine acceptance may help in planning for introduction of new vaccines to routine schedules. PMID:27104589

Evaluation of the acceptability of a vaccine against herpes zoster in the over 50 years old: an Italian observational study.

PubMed

Valente, Nicoletta; Lupi, Silvia; Stefanati, Armando; Cova, Marisa; Sulcaj, Najada; Piccinni, Lucia; Gabutti, Giovanni

2016-10-18

The aim of the study was to evaluate awareness of the varicella zoster virus and the acceptability of the newly available herpes zoster (HZ) vaccine in the over 50 years old general population. The research was observational. The study was carried out in Ferrara by administering a questionnaire to patients of the Local Health Authority (LHA), general practitioners (GPs) and Public Health Department outpatient clinics. The questionnaire was completed by 1001 residents of Ferrara Province. Of the respondents, 98% and 95% (57% female) were aware of varicella and HZ, respectively, but 91% were unaware of the HZ vaccine. Nevertheless, 58% declared that they were in favour of vaccination in this regard, and the acceptability of the vaccine was positively affected by: age (p=0.005); knowing someone who had suffered from HZ (p=0.05); being in favour of vaccination in general (p<0.0001); receiving advice to do so from their GP (p<0.0001) and willingness to get vaccinated even on a fee-paying basis (p<0.0001). Indeed, most (73%) respondents were willing to pay to get vaccinated, indicating an ideal cost of €50. Higher education (p=0.04), being in favour of vaccinations in general (p<0.0001) and GP advice (p<0.0001) positively affected this choice. Furthermore, 61% of the participants initially unfavourable (p<0.0001) to this immunisation would change their decision not to vaccinate thanks to their GP's advice. This study assessed the level of awareness and the attitudes of the population aged over 50 years, highlighting aspects to be focused on in the promotion of the HZ vaccine. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Real-World Effectiveness and Safety of a Live-Attenuated Herpes Zoster Vaccine: A Comprehensive Review.

PubMed

Ansaldi, Filippo; Trucchi, Cecilia; Alicino, Cristiano; Paganino, Chiara; Orsi, Andrea; Icardi, Giancarlo

2016-07-01

Herpes zoster (HZ) is a common, painful and debilitating disease caused by the reactivation of latent varicella-zoster virus in ganglia. This clinical event occurs more frequently in the elderly and those who are immunocompromised. The most common complication of HZ is post-herpetic neuralgia (PHN) which is responsible for the highest HZ-related burden of illness and is challenging to treat. Due to the important clinical and economic impact of HZ and PHN, and the suboptimal treatments that are currently available, HZ vaccination is an important approach to reduce the burden of illness. Currently, one-dose, live-attenuated vaccine is licensed in the United States and Europe to prevent HZ and it is included in some national immunization programs. The clinical efficacy, safety and tolerability of the vaccine has been demonstrated in two large phase III clinical trials, involving more than 38,000 and 22,000 individuals aged ≥60 and 50-59 years, respectively. This comprehensive review summarizes the extensive "real-world" effectiveness and safety data from both immunocompetent and immunocompromised individuals. These data confirm those from the clinical trials, supporting the use of HZ vaccine in clinical practice and provide evidence that the current recommendations for immunocompromised individuals should be revised. Funding for the editorial assistance, article processing charges, and open access fee for this publication was provided by Sanofi Pasteur MSD.

Chickenpox

MedlinePlus

Varicella; Chicken pox ... Chickenpox is caused by the varicella-zoster virus. It is a member of the herpesvirus family. The same virus also causes shingles in adults. Chickenpox can be spread very easily to others from ...

Risk Factors for Varicella Susceptibility Among Refugees to Toronto, Canada.

PubMed

Cadieux, Geneviève; Redditt, Vanessa; Graziano, Daniela; Rashid, Meb

2017-02-01

Several outbreaks of varicella have occurred among refugees. We aimed to estimate the prevalence of varicella susceptibility among refugees, and identify risk factors for varicella susceptibility. All refugees rostered at Crossroads Clinic in Toronto, Canada in 2011-2014 were included in our study. Varicella serology was assessed at the initial visit. Refugees' age, sex, education, time since arrival, and climate and population density of birth country were abstracted from the chart. Multivariate logistic regression was used to identify risk factors for varicella susceptibility. 1063 refugees were rostered at Crossroads Clinic during the study; 7.9 % (95 % CI 6.1, 9.7) were susceptible to varicella. Tropical climate (OR 3.20, 95 % CI 1.53, 6.69) and younger age (OR per year of age 0.92, 95 % CI 0.88-0.96) were associated with increased varicella susceptibility. These risk factors for varicella susceptibility should be taken into account to maximize the cost-effectiveness of varicella prevention strategies among refugees.

Herpes zoster vaccine effectiveness against incident herpes zoster and post-herpetic neuralgia in an older US population: a cohort study.

PubMed

Langan, Sinéad M; Smeeth, Liam; Margolis, David J; Thomas, Sara L

2013-01-01

Herpes zoster is common and has serious consequences, notably post-herpetic neuralgia (PHN). Vaccine efficacy against incident zoster and PHN has been demonstrated in clinical trials, but effectiveness has not been studied in unselected general populations unrestricted by region, full health insurance coverage, or immune status. Our objective was to assess zoster vaccine effectiveness (VE) against incident zoster and PHN in a general population-based setting. A cohort study of 766,330 fully eligible individuals aged ≥ 65 years was undertaken in a 5% random sample of Medicare who received and did not receive zoster vaccination between 1st January 2007 and 31st December 2009. Incidence rates and hazard ratios for zoster and PHN were determined in vaccinated and unvaccinated individuals. Analyses were adjusted for age, gender, race, low income, immunosuppression, and important comorbidities associated with zoster, and then stratified by immunosuppression status. Adjusted hazard ratios were estimated using time-updated Cox proportional hazards models. Vaccine uptake was low (3.9%) particularly among black people (0.3%) and those with evidence of low income (0.6%). 13,112 US Medicare beneficiaries developed incident zoster; the overall zoster incidence rate was 10.0 (9.8-10.2) per 1,000 person-years in the unvaccinated group and 5.4 (95% CI 4.6-6.4) per 1,000 person-years in vaccinees, giving an adjusted VE against incident zoster of 0.48 (95% CI 0.39-0.56). In immunosuppressed individuals, VE against zoster was 0.37 (95% CI 0.06-0.58). VE against PHN was 0.59 (95% CI 0.21-0.79). Vaccine uptake was low with variation in specific patient groups. In a general population cohort of older individuals, zoster vaccination was associated with reduction in incident zoster, including among those with immunosuppression. Importantly, this study demonstrates that zoster vaccination is associated with a reduction in PHN. Please see later in the article for the Editors' Summary.