[Vaccination in advanced age]. / Impfungen im höheren Lebensalter.

Infectious diseases are responsible for up to 5% of fatalities even in developed countries. In addition, there is an increasing susceptibility for infections in elderly people due to physiological aging of the immune system. The principles of vaccination are based on a targeted activation of the human immune system. Principally, a distinction is made between passive immunization, i.e. the application of specific antibodies against a pathogen and active immunization. In active immunization, i.e. vaccination, weakened (attenuated) or dead pathogens or components of pathogens (antigens) are administered. After a latency period that depends on the vaccine, complete immune protection is achieved and immunity is maintained for a certain period of time. In contrast to dead vaccines, by the use of live vaccines there is always a risk for infection with the administered vaccine. In passive immunization antibodies are administered. As a rule passive immunization is carried out in persons who have had contact with an infected person and in whom no or uncertain immunity against the corresponding disease is present. Based on the recommendations of the Standing Committee on Vaccination (STIKO), influenza, pneumococcal, herpes zoster, early summer meningoencephalitis (FSME) and travel vaccines are described.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 2: Treatment.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction in the incidence of postherpetic neuralgia (PHN) and other complications. The guideline development followed a structured and pre-defined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence-Based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this second part of the guideline, therapeutic interventions have been evaluated. The expert panel formally consented recommendations for the treatment of patients with HZ (antiviral medication, pain management, local therapy), considering various clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

European consensus-based (S2k) Guideline on the Management of Herpes Zoster - guided by the European Dermatology Forum (EDF) in cooperation with the European Academy of Dermatology and Venereology (EADV), Part 1: Diagnosis.

Herpes zoster (HZ, shingles) is a frequent medical condition which may severely impact the quality of life of affected patients. Different therapeutic approaches to treat acute HZ are available. The aim of this European project was the elaboration of a consensus-based guideline on the management of patients who present with HZ, considering different patient populations and different localizations. This interdisciplinary guideline aims at an improvement of the outcomes of the acute HZ management concerning disease duration, acute pain and quality of life of the affected patients and at a reduction of the incidence of postherpetic neuralgia and other complications. The guideline development followed a structured and predefined process, considering the quality criteria for guidelines development as suggested by the AGREE II instrument. The steering group was responsible for the planning and the organization of the guideline development process (Division of Evidence based Medicine, dEBM). The expert panel was nominated by virtue of clinical expertise and/or scientific experience and included experts from the fields of dermatology, virology/infectiology, ophthalmology, otolaryngology, neurology and anaesthesiology. Recommendations for clinical practice were formally consented during the consensus conference, explicitly considering different relevant aspects. The guideline was approved by the commissioning societies after an extensive internal and external review process. In this first part of the guideline, diagnostic means have been evaluated. The expert panel formally consented recommendations for the management of patients with (suspected) HZ, referring to the assessment of HZ patients, considering various specific clinical situations. Users of the guideline must carefully check whether the recommendations are appropriate for the context of intended application. In the setting of an international guideline, it is generally important to consider different national approaches and legal circumstances with regard to the regulatory approval, availability and reimbursement of diagnostic and therapeutic interventions.

Prevalence of antibodies against influenza A and B viruses in children in Germany, 2008 to 2010.

The prevalence of influenza A and B virus-specific IgG was determined in sera taken between 2008 and 2010 from 1,665 children aged 0-17 years and 400 blood donors in Germany. ELISA on the basis of whole virus antigens was applied. Nearly all children aged nine years and older had antibodies against influenza A. In contrast, 40% of children aged 0-4 years did not have any influenza A virus-specific IgG antibodies. Eightysix percent of 0-6 year-olds, 47% of 7-12 year-olds and 20% of 13-17 year-olds were serologically naïve to influenza B viruses. By the age of 18 years, influenza B seroprevalence reached approximately 90%. There were obvious regional differences in the seroprevalence of influenza B in Germany. In conclusion, seroprevalences of influenza A and influenza B increase gradually during childhood. The majority of children older than eight years have basal immunity to influenza A, while comparable immunity against influenza B is only acquired at the age of 18 years. Children aged 0-6 years, showing an overall seroprevalence of 67% for influenza A and of 14% for influenza B, are especially at risk for primary infections during influenza B seasons.

[Prevention of nosocomial transmission of human immunodeficiency virus (HIV) from HIV-positive healthcare workers. Recommendations of the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V]. / Prävention der nosokomialen Übertragung von humanem Immunschwächevirus (HIV) durch HIV-positive Mitarbeiterinnen und Mitarbeiter im Gesundheitswesen. Empfehlungen der Deutschen Vereinigung zur Bekämpfung der Viruskrankheiten (DVV) e.V. und der Gesellschaft für Virologie (GfV) e.V.

To the best of our knowledge, the German Association for the Control of Viral Diseases (DVV) e.V. and the Society for Virology (GfV) e.V. are the first in Europe to provide precise recommendations for the management of health care workers (HCWs) who are infected with human immunodeficiency virus (HIV). Requirements for HIV-infected HCWs need to be clearly defined. With a permanent viral burden of less than or equal to 50 copies/mL, HIV-positive HCWs are allowed to perform any surgery and any invasive procedure, as long as the infected HCW uses double-gloving, undergoes follow-up routinely by occupational medicine professionals, undergoes a quarterly examination of viral burden, and has a regular medical examination by a physician who has expertise in the management of HIV. Unrestricted professional activity is only possible with a strict compliance to take antiretroviral therapy and if the HIV-infected HCW strictly adheres to the recommended infection control procedures. Complete compliance with the recommendation almost certainly leads to no HIV transmission risk in patient care.

Seroprevalence of herpes simplex virus type 1 and type 2 in Thuringia, Germany, 1999 to 2006.

The prevalence of herpes simplex virus (HSV) type-specific IgG was determined in sera taken in 1999 to 2006 from 1,100 children aged 0­18 years, 800 blood donors and 200 pregnant women in Thuringia, Germany, using tests based on the HSV glycoproteins (g) gG. By the age of 10­12 years, HSV-1 IgG prevalence reached 57.3%, rising to 69.3% by the age of 16­18 years and to 78.0% by the age of 28­30 years. Between 2.7% and 4.7% of the children aged up to 15 years had HSV-2 antibodies, increasing to 7.3% at the age of 16­18 years and to 13.6% among adults. The prevalence of HSV-1 antibodies among girls was significantly lower than among boys and a significantly higher prevalence of HSV-2 IgG in women than in men was detected. The reduced incidence of HSV-1 infections during childhood, especially in girls, has to be followed up since a higher number of primary HSV-2 infections may result. Between 2.7% and 4.7% of all children tested seemed to acquire HSV-2 by intrauterine or neonatal infection. We also compared the use of gG-1 with gC-1: the agreement of 97.2% between the two ELISAs suggests that gG-1 and gC-1 can be considered equivalent antigenic targets.

Immune response of varicella vaccinees to different varicella-zoster virus genotypes.

The objective was to verify specific antibody response of varicella vaccinees to varicella-zoster virus (VZV) strains of different major clades and subclades circulating currently in Germany. The neutralization test and the fluorescent antibody to membrane antigen test measuring VZV glycoprotein (gp)-specific antibodies were used as methods. All VZV strains clustering into the main clades 1, 3 and 5 were neutralized by vaccine-induced antibodies and showed specific reaction with VZVgp-specific antibodies of vaccinees. In conclusion, this study provides first experimental evidence that varicella vaccines based on the Japanese Oka strain induce antibody response directed to VZV strains circulating currently in Germany.

Monitoring prevalence of varicella-zoster virus clades in Germany.

The global surveillance of varicella-zoster virus (VZV) clades is an important tool for investigation into viral evolution, host-virus interactions, role of immigration and travel for importation of viral strains as well as possible recombination events between wild- and vaccine-type VZV strains. In this prospective study, comprehensive data on the current distribution of VZV clades in Germany were collected. VZV strains from 213 patients with varicella and 109 with zoster were genotyped using the scattered single-nucleotide polymorphism method on the basis of sequencing open reading frames 1, 21, 22, 37, 50, 54 and 60. In varicella, clade 3 was detected in 45.5%, clade 1 in 30.0%, clade 5 in 21.1% and clade 2 in 0.9% of the cases. The analysis of zoster strains revealed clade 3 in 50.5%, clade 1 in 46.8%, clade 2 and clade 4 in 0.9% of the cases each. Five strains from varicella and one strain from zoster could not be attributed to any of the major and provisional VZV clades. Statistical analysis verified significantly lower frequency of clade 1 and significantly higher frequency of clade 5 in patients with varicella compared to zoster. In addition, varicella patients with clade 5 strains were significantly younger than the patients with clade 3. In conclusion, almost one half of VZV infections in Germany were caused currently by VZV clade 3. In primary VZV infection, nearly 20% of clade 1 has been replaced by clade 5 that might spread more effectively in the population than the European VZV clades.

Virucidal efficacy of povidone-iodine-containing disinfectants.

AIMS: The objective of this study was to evaluate virucidal efficacy of the commercially available povidone-iodine formulations Betaisodona solution and Betaseptic Mundipharma (Mundipharma). METHODS AND RESULTS: The quantitative suspension test for virucidal testing of biocides according to the German guideline was used as method. The use of Betaisodona solution resulted in virucidal efficacy, corresponding to >or=10(4)-fold reduction in viral titre, against vaccinia virus, bovine viral diarrhoea virus and polyomavirus SV40 within 0.5 min and adenovirus type 5 within 3-5 min without and with organic load. For inactivation of the most resistant poliovirus type 1, a time interval of >or=60 min was needed. By contrast, Betaseptic Mundipharma inactivated significantly all model viruses for virucidal testing including poliovirus type 1 within 5 min independently from the addition of proteins. CONCLUSIONS: Betaisodona solution shows a good efficacy against enveloped model viruses as well as against some nonenveloped human viruses, e.g. adenovirus and polyomavirus. Betaseptic Mundipharma has an excellent virucidal efficacy including the inactivation of the most resistent poliovirus type 1. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of this study make Betaseptic Mundipharma suitable for virucidal disinfection of the skin within short time intervals.

[Zoster vaccine]. / Zoster-Vakzine.

In Germany, a vaccine (Zostavax) to prevent herpes zoster and postherpetic neuralgia (PHN) in adults aged 50 years and older has been available since October 2009. The efficacy of this attenuated high-dose live vaccine was evaluated in a double-blind randomised, placebo-controlled trial involving more than 38,000 immunocompetent adults aged >or= 60 years. Compared to placebo the vaccine reduced the frequency of herpes zoster by 51 % and the incidence of PHN by 67 %. Overall, the burden of illness was reduced by 61 %. The course of diseases occurring among the vaccine recipients was clearly milder and the risk for complications was lower than among the placebo recipients. Although the vaccine efficacy against herpes zoster declined with advancing age of the vaccinees, subjects older than 70 years also benefited from vaccination because the burden of illness was considerably reduced. To the best of our present knowledge the protective effect of zoster vaccine persists for at least 7 years post-vaccination. The need for, or timing of, revaccination has not yet been determined. Zostavax has been well tolerated. It can be concomitantly administered with inactivated influenza vaccine at separate sites. Zoster and pneumococcal vaccines should not be given concomitantly.

Phenotypic and genotypic characterization of acyclovir-resistant clinical isolates of herpes simplex virus.

Sixteen herpes simplex virus type 1 (HSV-1) and four type 2 (HSV-2) isolates resistant to acyclovir (ACV) were characterized retrospectively for drug resistance. Phenotypic testing was performed by means of tetrazolium reduction assay and genotypic analysis was carried out by sequencing of thymidine kinase (TK) and DNA-polymerase (pol) genes. All strains were characterized as cross-resistant to penciclovir, brivudin and susceptible to cidofovir. In addition, three strains were resistant to foscarnet. Genotypic analysis revealed two to seven non-synonymous mutations in the TK gene of HSV-1 and one to seven non-synonymous mutations in the DNA pol gene of HSV-1 and 2 associated with the gene polymorphism. Seventeen strains contained at least one non-synonymous resistant-related mutation in the TK gene and three strains, which were additionally foscarnet-resistant, revealed one resistance-associated mutation in the DNA pol gene. In most strains, resistant-related mutations in TK gene represented frameshift mutations and single non-synonymous nucleotide substitutions of conserved gene regions. However, numerous amino acid changes could not be interpreted clearly as accounting for resistance. In conclusion, further studies, e.g. site-directed mutagenesis experiments are required to characterize mutations of the TK and DNA pol genes in ACV-resistant viral strains as part of viral gene polymorphism or as cause of drug resistance.

Variability of immediate-early gene 62 in german varicella-zoster virus wild-type strains.

Varicella-zoster virus strains of European genotypes have developed a high variability of open reading frame (ORF) 62 during their occurrence over many years in Germany. M1 strains in Germany display a uniform ORF 62 pattern, suggesting that these strains were introduced from Africa and/or Asia via few sources during the last years.

Short version of the German evidence-based Guidelines for prophylactic vaccination against HPV-associated neoplasia.

Persistent infection with HPV 16 and 18 has been causally associated with the development of cervical cancer and its precursor lesions as well as with other carcinomas and their precursors, e.g. some vulvar and vaginal cancers. Furthermore HPV 6 and 11 are responsible for anogenital condylomata acuminata in more than 90% of cases. With the recently developed prophylactic bivalent (HPV 16 and 18) and quadrivalent (HPV 6, 11, 16 and 18) vaccines, it is possible to prevent infection of the cervical epithelium and other squamous epithelia, the development of premalignant lesions and, in the case of the quadrivalent vaccine, the development of condylomata acuminata. The following paper represents a summary of the full-text version of the German evidence-based Guidelines, including all evidence-based recommendations regarding the safety as well as the efficacy of the vaccines in preventing CIN, VIN/VaIN, genital warts and other HPV-associated lesions.

[Herpes zoster and postherpetic neuralgia - prevention by vaccination?]. / Herpes zoster und postherpetische Neuralgie - Vorbeugung durch Impfung?

Herpes zoster is caused by reactivation of latent varicella-zoster virus (VZV), which had remained latent in the dorsal root or cranial nerve ganglia since the primary infection. The risk of developing zoster increases significantly with age, the vast majority of zoster cases occuring in persons over 50 years. The most frequent and debilitating complication of zoster in immunocompetent patients is postherpetic neuralgia (PHN). In the absence of antiviral therapy, clinical studies have found up to 30 - 45 % of persons over 60 years of age to experience pain persisting for more than 6 months. Systemic antiviral therapy is able to shorten the healing process of acute zoster and to prevent or alleviate pain and other complications, when given within 72 hours after appearance of the rash. About 20 % of patients older than 50 years continue to have pain six months after appearance of rash, despite antiviral treatment. A live attenuated VZV vaccine was licensed in Europe in 2006 for the prevention of zoster in individuals from the age of 60 years. Findings of a large clinical trial have shown that the zoster vaccine reduced the burden of illness caused by zoster among people 60 years of age or older by 61 % and the incidence of PHN by 67 %. Compared with controls, subjects who received the vaccine were 51 % less likely to develop zoster.