[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.

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.

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.

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.

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.

In vitro cultivation and cryopreservation of duck embryonic hepatocytes.

Hepatitis B-virucidal testing of biocides in quantitative suspension tests using duck hepatitis B virus (DHBV) requires primary duck embryonic hepatocytes for viral propagation. To improve the test system and availability of these cells, commercial culture plates with different growth surfaces were tested for cell cultivation and different approaches for cryopreservation of hepatocyte suspension were examined. After 12 days of culture, the largest amounts of hepatocytes were grown in CellBIND and TTP plates and CellBIND surface showed the lowest tendency of monolayer detachment nearly comparable with collagen 1-coated CELLCOAT plates. For cryopreservation of hepatocyte suspension, the use of growth medium supplemented with fetal calf serum (FCS) and dimethyl sulfoxide (ME(2)SO), FCS supplemented with ME(2)SO or cryosafe-1 as cryoprotective agents provided the highest rates of surviving cells after thawing. The freezing-thawing process did not significantly reduce the susceptibility of hepatocytes to infection with DHBV. In conclusion, plates without collagen 1 such as CellBIND are recommended for cultivation of primary duck embryonic hepatocytes in infectivity experiments of DHBV for virucidal testing of biocides. The use of cryopreserved hepatocytes is possible when freshly isolated cells from the liver of duck embryos are not available.

Seroprevalence of influenza A and B in German infants and adolescents.

The objective of this study was to provide seroepidemiological information on influenza A and B antibodies in children and adolescents. Viral immunoglobulin G antibodies were determined retrospectively using enzyme-linked immunosorbent assays in a group of 1,111 children and adolescents. Sera (809) from healthy adult blood donors served as controls. In children, the prevalence of antibodies against influenza A was 82.0% and against influenza B 9.6%, whereas in adults the prevalence of antibodies against influenza A was calculated as 99.4% and against influenza B 56.7%. After decline of maternal antibodies during the first year of life, there was an increase of prevalence of influenza A antibodies up to 100% by the age of 12 years. In contrast, only 1-2% of children up to 9 years had influenza B antibodies increasing to 25% by the age of 18 years and to 70% among adults aged 30 years. Children aged 0-6 years had significantly lower concentrations and >12-15-year-old adolescents had significantly higher concentrations of antibodies against influenza A than adults. For all age groups of children and adolescents, significantly lower antibody concentrations against influenza B were measured in comparison to the blood donor control group. In conclusion, the annual influenza vaccination in children and adolescents may improve considerably the protection against influenza virus infection occurring during epidemics.

Testing thermal resistance of viruses.

Representative viral strains recommended for virucidal testing of biocides in human medicine were used for testing viral resistance to dry heat using the new Keredusy hot instrument. The results demonstrate that poliovirus type 1 could be inactivated by treatment at 75 degrees C for 1 h. For inactivation of adenovirus type 5, 2 h at 85 degrees C was needed. The infectivity of polyomavirus SV40 could only be influenced significantly by a temperature of 95 degrees C over a period of 1 h, whereas vaccinia virus and bovine viral diarrhea virus needed a time interval of 2 h at 95 degrees C. The infectivity of bovine parvovirus could not be influenced significantly by exposure to 95 degrees C for 2 h. In conclusion, human viruses and their surrogates for testing biocides may have a considerable thermal resistance that makes them difficult to be inactivated only by dry heat.

Hexon denaturation of human adenoviruses by different groups of biocides.

Human adenoviruses have often been used as surrogates for testing broad-spectrum virucidal efficacy of biocides. However, recent studies have shown that members of this group of viruses have quite different chemical sensitivities and only serotypes 5 and 44 can be recommended as model viruses. In this study, the hexon protein of the serotypes 1, 2, 5, 6 and 8 was exposed to biocides and subsequently detected by western blotting and the RPS Adeno Detector. Only peracetic acid (PAA) at a relatively high concentration of 0.5% led to complete denaturation of hexon protein within 60 min. This effect was uniform for all adenoviruses tested and was not observed after exposure to 0.05-2.5% povidone-iodine (PVP-I) or 0.7% formaldehyde. However, viral infectivity and genome integrity were influenced by PVP-I and formaldehyde and lower concentrations of PAA. In conclusion, the hexon protein of human adenoviruses shows an unexpectedly high and uniform resistance to chemical biocides. The different chemical sensitivities of adenoviruses cannot be explained by the sensitivity of this main structural compound, but the present findings provide new insights into the virucidal action of disinfectants.

Genotyping of different varicella vaccine strains.

BACKGROUND: Little is known about single nucleotide polymorphism (SNP) in different lots of varicella vaccines distributed by the manufacturers. Recently, the genetic analysis of several genomic regions revealed a polymorphism in different vaccine lots of Varilrix manufactured by GlaxoSmithKline. These findings need attention since mutations in the vaccine strain could result in changes of virulence and efficacy of the vaccine. OBJECTIVES: To identify SNPs in three varicella vaccine lots of Varilrix and to compare the results with that of Varivax as well as the published sequences of the Oka vaccine strain (V-Oka) and its parental virus (P-Oka). STUDY DESIGN: The open reading frames (ORF) 1, 6, 10, 21, 50, 54, and 62 were analyzed by sequencing of amplified DNA fragments. RESULTS: Wild-type nucleotides identical to that of P-Oka and/or the European wild-type reference strain Dumas and in contrast to V-Oka could be identified in ORF 1 of a Varilrix vaccine lot distributed in 1991. In the ORF 62 probably responsible for attenuation of V-Oka, this vaccine strain contained 16 SNPs which were nearly all wild-type-like. By contrast, different lots of the Varivax vaccine revealed uniform sequencing results. The vaccine Varilrix 1999 showed a high similarity to the Varivax vaccine currently available. CONCLUSIONS: The obvious genetic diversity of different lots of the varicella vaccine Varilrix cannot be explained with the coexistence of several strain variants in the vaccine, but most likely with different seed lot preparations used for vaccine production.

Validation of biocides against duck hepatitis B virus as a surrogate virus for human hepatitis B virus.

The use of a surrogate virus, namely duck hepatitis B virus (DHBV), has been recommended for testing the virucidal activity of chemical biocides against hepatitis B virus. To date, however, this model has not been recognized as a standard test in European countries, as its laboratory use is associated with considerable difficulties. As previous studies have demonstrated, several alternative procedures may improve the validation of DHBV infection in a cell culture system. Using indirect immunofluorescent antigen staining and the light cycler real-time polymerase chain reaction (PCR) technique, the virucidal activity of peracetic acid (PAA), povidone-iodine (PVP-I) and formaldehyde was tested against DHBV obtained from congenitally infected ducks or prepared from the transfected hepatoma D2 cell line. The results demonstrated that inactivation of DHBV from the D2 cell line was achieved with lower concentrations of the biocides and within shorter exposure time intervals. These lower concentration-exposure time values for DHBV from D2 cells in comparison with DHBV from infected ducks indicated a higher sensitivity of the virus derived from D2 cells. In addition, concentrations of PAA and PVP-I that significantly inactivated DHBV in suspension tests were not able to destroy the viral genome. In conclusion, DHBV from congenitally infected ducks should be used for virucidal testing of chemical biocides against DHBV; DHBV prepared from D2 cells is unsuitable due to its higher sensitivity to biocides. Indirect immunofluorescent staining allows reliable detection of DHBV infectivity, whereas the hepadnavirucidal effect can be evaluated by quantitative PCR.