Impaired antibody memory to varicella zoster virus in HIV-infected children: low antibody levels and avidity*

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.

Swiss recommendations for the management of varicella zoster virus infections

Infections with varicella zoster virus (VZV) are common viral infections associated with significant morbidity. Diagnosis and management are complex, particularly in immunocompromised patients and during pregnancy. The present recommendations have been established by a multidisciplinary panel of specialists and endorsed by numerous Swiss medical societies involved in the medical care of such patients (Appendix). The aim was to improve the care of affected patients and to reduce complications.

Novel approach for genotyping varicella-zoster virus strains from Germany

In this study, we present a novel genotyping scheme to classify German wild-type varicella-zoster virus (VZV) strains and to differentiate them from the Oka vaccine strain (genotype B). This approach is based on analysis of four loci in open reading frames (ORFs) 51 to 58, encompassing a total length of 1,990 bp. The new genotyping scheme produced identical clusters in phylogenetic analyses compared to full-genome sequences from well-characterized VZV strains. Based on genotype A, D, B, and C reference strains, a dichotomous identification key (DIK) was developed and applied for VZV strains obtained from vesicle fluid and liquor samples originating from 42 patients suffering from varicella or zoster between 2003 and 2006. Sequencing of regions in ORFs 51, 52, 53, 56, 57, and 58 identified 18 single-nucleotide polymorphisms (SNPs), including two novel ones, SNP 89727 and SNP 92792 in ORF51 and ORF52, respectively. The DIK as well as phylogenetic analysis by Bayesian inference showed that 14 VZV strains belonged to genotype A, and 28 VZV strains were classified as genotype D. Neither Japanese (vaccine)-like B strains nor recombinant-like C strains were found within the samples from Germany. The novel genotyping scheme and the DIK were demonstrated to be practical and simple and allow the highly efficient replication of phylogenetic patterns in VZV initially derived from full-genome DNA sequence analyses. Therefore, this approach may allow us to draw a more comprehensive picture of wild-type VZV strains circulating in Germany and Central Europe by high-throughput procedures in the future.

Prospective surveillance of varicella-zoster virus infections in an out-patient setting in Switzerland

Limited data are available on the clinical impact of varicella in the ambulatory setting. Our goal was to determine real-life data on the clinical outcomes, medical management, and resource utilization in patients with varicella in Switzerland, a country without a universal immunization program against varicella. A total of 236 patients (222 = 94% primarily healthy individuals) with a clinical diagnosis of varicella were recruited by pediatricians and general practitioners. Age range of patients was 0-47 years with a median of 5 years. The great majority of patients (179 = 76%) were

Pharyngolaryngeal involvement by varicella-zoster virus

INTRODUCTION Involvement of cranial nerves V, VII, and VIII by varicella-zoster virus (VZV) is widely reported in the literature, whereas involvement of cranial nerves IX and X is rarer and therefore poorly characterized. MATERIAL AND METHODS We performed a systematic review of the literature through MEDLINE (up to January 2012). We selected cases reporting pharyngolaryngeal involvement by VZV and extracted clinical features, complementary studies, treatments, and outcome. We added three cases to the existing literature. RESULTS Of the 65 screened articles, 38 were included reporting 54 cases. The main clinical features were odynodysphagia and dysphonia reflecting underlying hemipharyngolaryngeal palsy. Vesicles were seen in 66% of the patients. Besides the involvement of cranial nerves IX and X, concomitant involvement of other cranial nerves was seen in 48% of the cases. The most concerned nerves were cranial nerves VII and VIII. Virological tests (63%) and imaging (28%) were performed, with the latter being systematically normal. Seventy-two percent of patients were treated with antiviral agents and/or corticosteroids. Twenty-six percent of patients made a full recovery while the remaining had some persistent deficits. We did not find statistically significant differences in outcomes according to age or treatments received. CONCLUSIONS Pharyngolaryngeal involvement by VZV is rare and seldom restricted to the ninth and tenth cranial nerves. It occurs mostly within the context of cranial polyneuropathy. Regardless of the treatment, full recovery is rare and long-term sequelae persist in many cases, especially with speech and swallowing impairment. Close monitoring and follow-up are therefore essential.

Varicella zoster virus reactivation after autologous SCT is a frequent event and associated with favorable outcome in myeloma patients.

The occurrence of varicella zoster virus (VZV) reactivation is increased after allogeneic transplantation, whereas limited data are available for herpes zoster (HZ) after autologous SCT (ASCT). We determined the incidence and the prognostic significance of HZ and its correlation with VZV serology in 191 consecutive myeloma patients undergoing high-dose melphalan chemotherapy with ASCT. We found that VZV reactivation occurred in 57 (30%) patients, in 8.5% during induction and in 21.5% after ASCT peaking at 8 months after ASCT. Disease burden due to HZ was assessed as high or rather high in 70% of the patients. By immune fluorescence and Serion Elisa VZV IgG assessment, 90.8% of all patients had specific anti-VZV antibodies at ASCT. Lower specific antibody titers at transplantation were observed in patients with HZ after ASCT than in those without reactivation (P=0.009). Finally, OS was better in myeloma patients with HZ after ASCT compared with patients without HZ (P=0.007). Our data indicate that VZV reactivation after ASCT is a frequent event carrying a significant disease burden and it is associated with improved survival. Low levels of specific VZV antibodies at ASCT suggest increased vulnerability for VZV reactivation.Bone Marrow Transplantation advance online publication, 19 January 2015; doi:10.1038/bmt.2014.290.

Keratitis durch Herpes-simplex- und Varizella-zoster-Virus

Herpes-simplex- und Varizella-zoster-Viren sind die häufigsten Ursachen viraler Keratitiden. Bei chronisch rezidivierendem Verlauf entstehen oft visuslimitierende Komplikationen. Typische Verlaufsformen sind die epitheliale Keratitis (dendritisch/geografisch), stromale Keratitis (infektiös und/oder immunologisch), Endotheliitis (disziform) und neurotrophe Keratopathie (metaherpetische Keratitis). Beim Zoster ophthalmicus kommt die Problematik der postherpetischen Neuralgie hinzu. Mit den verfügbaren Virustatika stehen potente Wirkstoffe zur Verfügung, auch zur Schubprophylaxe. Sobald immunologische Prozesse eine zentrale Rolle spielen, ist der gezielte Einsatz von topischen Kortikosteroiden oder Ciclosporin A notwendig. Der Epithelschluss kann mit Tränenersatzmitteln, Kontaktlinsen oder einer Amnionmembran-Transplantation unterstützt werden. Die Erfolgsrate von elektiven Keratoplastiken kann durch eine Langzeitprophylaxe mit systemischen Virustatika verbessert werden.

Economic evaluation of varicella vaccination in Swiss children and adolescents

This study explores the effects of three different 2-dose varicella zoster virus (VZV) vaccination strategies in Switzerland. The EVITA model was used to assess clinical benefits and costs of strategies (1) vaccination of 11-15 year old adolescents with a negative or uncertain history for chickenpox, (2) universal vaccination of toddlers at age 1 to 2 years, and (3) strategy 2 plus catch-up vaccination of 11-15 year old susceptible adolescents. The cost-effectiveness analysis compares strategies 2 and 3 versus strategy 1 (current vaccination policy in Switzerland). Probabilities for clinical outcomes and medical resource utilization were derived from a real-world survey among Swiss pediatricians and general practitioners including 236 individuals with VZV infection, published information on varicella complications, and expert opinion. Costs of medical resource utilization represent official Swiss medical tariffs. The model predicts both universal childhood vaccination strategies to be more effective in reducing varicella disease burden compared to strategy 1. Economically, both universal childhood vaccination strategies with or without catch-up result in net savings from the societal perspective reflected by a benefit cost ratio (BCR) of 1.22 or 1.29, respectively. In contrast, the model predicts net costs from the payer perspective (BCR of 0.27 and 0.30, respectively). These economic findings are comparable to those reported from other similar evaluations. However, due to the recent recommendation for using a 2-dose varicella vaccination schedule, our economic results for Switzerland are somewhat less favorable than those for other country analyses in which a less expensive 1-dose vaccination regimen for toddlers has been studied.

Gustatory dysfunction after mandibular zoster

Varicella zoster, limited to the mandibular nerve, is rare. Classical symptoms are pain, hypesthesia and vesicular eruption restricted to the third trigeminal segment (V3). Little is known on taste affection after mandibular nerve zoster. We report two cases of patients suffering from mandibular zoster associated with subjective taste disorder. In both cases, gustatory measures confirmed ipsilateral hemiageusia of the anterior two-thirds of the tongue. After 2 months, the symptoms regressed and psychophysical measures came back to normal values, whereas post-zoster neuralgia lasted for more than 1 year. Gustatory dysfunction is a possible symptom after mandibular nerve zoster. In contrast to post-zoster neuralgia, taste function seems to recover quickly.

Inflammatory markers in pediatric stroke: An attempt to better understanding the pathophysiology

BACKGROUND The mechanisms of childhood and perinatal arterial ischemic stroke (AIS) are poorly understood. Multiple risk factors include cerebral arteriopathy, congenital cardiac disease, infection, sickle cell disease, and maternal-fetal conditions in neonates. For infections and parainfectious conditions being the most important a possible inflammatory pathophysiology has long been suspected. This pilot study aims to detect, whether there are any abnormalities of inflammatory markers associated with childhood and neonatal stroke. METHODS The concentration of 23 different metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), endothelial factors, vascular cell adhesion proteins, and cytokines in plasma were measured in 12 children with AIS, 7 healthy age matched controls and 6 full term neonates with perinatal AIS. RESULTS At the time of the acute event children with AIS had significantly elevated levels of MMP-9, TIMP4, IL-6, IL-8 and CRP compared to controls (p < 0.05). Except for lower IL-6 and CRP levels the pattern of children with a history of varizella-zoster virus (VZV) and other viral infections did not differ to the non-infectious group. Median levels of MMP-1, MMP-2, TIMP-1, TIMP-2, sE-selectin, sICAM-1, sVCAM-1, IL-8, IL-10, TNF-alpha, VEGF, Fetuin A were found to be higher in the neonatal group when compared with older children. CONCLUSION This pilot study supports the assumption of an inflammatory process and up-regulation of metalloproteinases and their inhibitors, and altered pattern of circulating pro-inflammatory cytokines, CRP and vWF levels in pediatric and neonatal AIS. It highlights the feasibility but also difficulties for similar larger future studies that should aim to clarify childhood stroke etiopathogenesis and consecutive further therapeutic options.

Determinants of vaccine immunity in the cohort of human immunodeficiency virus-infected children living in Switzerland

BACKGROUND: Human immunodeficiency virus (HIV)-infected children are at increased risk of infections caused by vaccine preventable pathogens, and specific immunization recommendations have been issued. METHODS: A prospective national multicenter study assessed how these recommendations are followed in Switzerland and how immunization history correlates with vaccine immunity. RESULTS: Among 87 HIV-infected children (mean age: 11.1 years) followed in the 5 Swiss university hospitals and 1 regional hospital, most (76%) had CD4 T cells >25%, were receiving highly active antiretroviral treatment (79%) and had undetectable viral load (60%). Immunization coverage was lower than in the general population and many lacked serum antibodies to vaccine-preventable pathogens, including measles (54%), varicella (39%), and hepatitis B (65%). The presence of vaccine antibodies correlated most significantly with having an up-to-date immunization history (P<0.05). An up-to-date immunization history was not related to age, immunologic stage, or viremia but to the referral medical center. CONCLUSIONS: All pediatricians in charge of HIV-infected children are urged to identify missing immunizations in this high-risk population.