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Introduction Several chronic underlying conditions (UCs) are known to be risk factors for developing herpes zoster (HZ) and to increase the severity of HZ and its risk of recurrence. The aim of this study was to investigate the incidence and recurrence of HZ in adult patients with one or multiple UCs. Methods A retrospective cohort study based on claims data representing 13% of the statutory health insurance population from 2007 to 2018 in Germany was performed. Patients aged ≥ 18 years were included when at least one of the following UCs was diagnosed: asthma, chronic heart failure, chronic obstructive pulmonary disease (COPD), coronary heart disease (CHD), depression, diabetes mellitus type 1 or 2, and rheumatoid arthritis (RA). Exact matching was used to account for differences in the distribution of age and sex between the case and matched control cohorts. Multi-morbidity was considered in sensitivity analyses by analyzing patients with only one UC. Results Patients with asthma, CHD, COPD, depression, and RA had, on average, a 30% increased risk of developing acute HZ compared to patients without any UC. RA was found to have the highest odds ratio among these conditions, varying from 1.37 to 1.57 for all age groups. Patients with depression also showed a high risk of developing HZ. Analysis of recurrence indicated that patients with at least one UC in the age groups 18–49 years and 50–59 years had the highest risk for a recurrent HZ. After experiencing a first recurrence, patients, regardless of age group, had a two- to threefold higher risk for a second recurrence. Conclusion This study of representative claims data shows a higher HZ incidence and recurrence frequency in patients with UCs. These results provide relevant information for national health care guidelines and disease management programs. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00535-7., Plain Language Summary Shingles is caused by the reactivation of the chickenpox virus and is characterized by a painful skin rash with blisters, commonly occurring on the trunk. Underlying conditions (UCs) are conditions that persist for a long time, require ongoing medical attention, and are rarely completely cured (chronic conditions). UCs can increase the severity, the risk, and the frequency of shingles. Here, data from a large German health care insurance provider was used to investigate whether patients with one or more UCs have a higher risk for getting shingles compared to healthy people. In particular, patients with asthma, chronic heart failure, chronic obstructive pulmonary disease, coronary heart disease, depression, diabetes, and rheumatoid arthritis were investigated. The study shows that patients with asthma, coronary heart disease, chronic obstructive pulmonary disease, depression, and rheumatoid arthritis have, on average, a 30% higher risk of developing shingles, regardless of their age. The risk of developing shingles two or more times is also higher for patients with at least one UC, with those aged 18–59 experiencing an even greater risk. It was found that patients with an UC are more exposed to develop shingles and that younger patients have a higher risk of a recurrent episode. The findings provide important information for the development or adaption of national health care guidelines and shingles vaccination recommendations. Supplementary Information The online version contains supplementary material available at 10.1007/s13555-021-00535-7.

Background Varicella and herpes zoster (HZ), diseases both caused by the varicella zoster virus (VZV), are vaccine-preventable. However, the hypothesis that childhood varicella vaccination may increase the incidence of HZ hinders varicella universal routine vaccination (URV) implementation in many countries. Methods This non-systematic and narrative review of the literature considers the burden of varicella and HZ, and the effectiveness of the respective vaccines. We present the factors involved in the interplay between varicella vaccination and HZ incidence, including the roles of exogenous and endogenous boosting. We review HZ incidence model predictions, and compare these with real-world evidence, which has accumulated since varicella URV was introduced. Conclusion Although more research and longer surveillance are needed, available real-world evidence has not confirmed the model-predicted increase in HZ incidence, associated with childhood varicella URV. Although there is a rising incidence of HZ globally, this trend appears to be predominantly the result of an aging population. Vaccination against varicella in childhood provides significant benefits with respect to the medical, societal and economic burdens of the disease. Therefore, a theoretical concern of an increased burden of HZ with varicella vaccination programs should not prevent children from being protected against the disease.

Im Alter ist die Grippe besonders gefahrlich: Krankenhausaufnahmen und schwere Komplikationen sind bei infizierten Senioren haufig und die Mortalitat ist erhoht. Den besten Schutz bietet die Grippeimpfung, die aber bisher in Deutschland nur jeder dritte uber 60-Jahrige erhalt.

Im Alter wird das Immunsystem schwacher. Senioren sind daher besonders anfallig fur Infektionen und schwere Krankheitsverlaufe. Auch das Ansprechen auf Impfungen kann bei Betagten vermindert sein.

Italy (in pilot regions) and Germany (nationwide) were the first European countries to introduce universal varicella vaccination (UVV) programs. A systematic review was performed to assess varicella epidemiology before UVV programs and the impact of 1-dose and 2-dose UVV programs in Italy and Germany. Italy implemented 1- or 2-dose UVV programs successively in eight pilot regions between 2003 and 2011 and nationwide in 2017. Germany implemented 1- and 2-dose UVV programs in 2004 and 2009, respectively. While Italy had two nationwide surveillance systems in place for varicella in the pre-vaccination era, in Germany, a mandatory notification system for varicella was only introduced in the New Federal States 2 years before the 1-dose UVV implementation. Substantial reductions in moderate/severe varicella and varicella-related hospitalization incidence occurred during the 1-dose era. Further reductions were reported in Italy and Germany after the recommendation of a second dose in a long or short schedule, respectively. Different benefit-risk evaluations of a tetravalent varicella-containing vaccine (MMRV) used as a first dose led to different recommendations (MMRV versus MMR+V) in these countries. Vaccination strategies in both countries tailored to country-specific needs and goals led to a reduction in varicella-related health care hospitalization costs.

The present guidelines are aimed at residents and board-certified specialists in the fields of dermatology, ophthalmology, ENT, pediatrics, neurology, virology, infectious diseases, anesthesiology, general medicine and any other medical specialties involved in the management of patients with herpes zoster. They are also intended as a guide for policymakers and health insurance funds. The guidelines were developed by dermatologists, virologists, ophthalmologists, ENT physicians, neurologists, pediatricians and anesthesiologists/pain specialists using a formal consensus process (S2k). Readers are provided with an overview of the clinical and molecular diagnostic workup, including antigen detection, antibody tests and viral culture. Special diagnostic situations and complicated disease courses are discussed. The authors address general and special aspects of antiviral therapy for herpes zoster and postherpetic neuralgia. Furthermore, the guidelines provide detailed information on pain management including a schematic overview, and they conclude with a discussion of topical treatment options.

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.

The highest burden of pediatric vaccine-preventable disease is found in developing nations where resource constraints pose the greatest challenge, impacting disease diagnosis and surveillance as well as the implementation of large scale vaccination programmes. In November 2012, a Working Group Meeting convened in Casablanca to describe and discuss the status with respect to 8 vaccine-preventable diseases (pertussis, pneumococcal disease, measles-mumps-rubella-varicella (MMRV), rotavirus and meningococcal meningitis) to identify and consider ways of overcoming obstacles to pediatric vaccine implementation. Experts from Europe, Russia, the Commonwealth of Independent States, the Middle East, Africa and South East Asia participated in the meeting. A range of region-specific needs and barriers to uptake were discussed. The aim of this article is to provide a summary of the ongoing status with respect to pediatric vaccine preventable disease in the countries represented, and the experts' opinions and recommendations with respect to pediatric vaccine implementation.

Die Alterung des Immunsystems, die Immunseneszenz, fuhrt zu einer Zunahme von Infektionen im Alter mit meist oligosymptomatischem und teils schwerem Verlauf. Sie reduziert die Immunantwort auf Impfungen, weshalb starker immunogene Vakzine fur Altere vorteilhaft sind. Die Standige Impfkommission (STIKO) empfiehlt fur Personen ab 60 Jahren die jahrlich zu wiederholende Influenza-Impfung als Standardimpfung sowie fur Pflegeheimbewohner als Indikationsimpfung. Einmalig ab dem 60. Lebensjahr sollen die Pneumokokken-Polysaccharidimpfung sowie die Komplettierung bei unvollstandiger Td-Grundimmunisierung (Tetanus, Diphtherie) und die regelmasige Auffrischungsimpfung mit dem Td-Kombinationsimpfstoff erfolgen. Einmalig sollen auch Senioren gegen Pertussis mit dem Tdap-Kombinationsimpfstoff geimpft werden. Die nun auch fur Erwachsene zugelassene Pneumokokken-Konjugatvakzine bleibt in der STIKO-Empfehlung bisher unberucksichtigt, ebenso der Impfstoff zur Pravention des Herpes zoster und der Post-Zoster-Neuralgie.

Erkrankt ein Patient an Gurtelrose, steigt u. a. sein Risiko fur kardiovaskulare Komplikationen an. Neben der antiviralen Therapie, die das Schlaganfallrisiko verringert, ist auch die Zosterimpfung als Prophylaxemasnahme bei alteren Menschen sinnvoll.

Background A controversy exists about the potential effect of childhood varicella vaccination on Herpes Zoster (HZ) incidence. Mathematical models projected temporary HZ incidence increase after vaccine introduction that was not confirmed by real-world evidence. These models assume that absence of contacts with infected children would prevent exogenous boosting of Varicella-Zoster-Virus (VZV) immunity and they do not include an endogenous VZV immunity-boosting mechanism following asymptomatic VZV reactivation. This study aims to explore the effect of various assumptions on exogenous and endogenous VZV immunity-boosting on HZ incidence in the general population after introduction of routine childhood varicella vaccination. Methods An age-structured dynamic transmission model was adapted and fitted to the seroprevalence of varicella in France in absence of vaccination using the empirical contact matrix. A two-dose childhood varicella vaccination schedule was introduced at 12 and 18 months. Vaccine efficacy was assumed at 65%/95% (dose 1/dose 2), and coverage at 90%/80% (dose 1/dose 2). Exogenous boosting intensity was based on assumptions regarding HZ-immunity duration, age-dependent boosting effect, and HZ reactivation rates fitted to observed HZ incidence. Endogenous boosting was the same as pre-vaccination exogenous boosting but constant over time, whilst exogenous boosting depended on the force of infection. Five scenarios were tested with different weightings of exogenous (Exo) - endogenous (Endo) boosting: 100%Exo–0%Endo, 75%Exo–25%Endo, 50%Exo–50%Endo, 25%Exo–75%Endo, 0%Exo–100%Endo. Results HZ incidence before varicella vaccination, all ages combined, was estimated at 3.96 per 1000 person-years; it decreased by 64% by year 80 post vaccine introduction, for all boosting assumptions. The 100%Exo-0%Endo boosting scenario, predicted an increase in HZ incidence for the first 21 years post vaccine introduction with a maximum increase of 3.7% (4.1/1000) at year 9. However, with 0%Exo-100%Endo boosting scenario an immediate HZ decline was projected. The maximum HZ incidence increases at 10, 3, and 2 years post vaccination were 1.8% (75%Exo-25%Endo), 0.8% (50%Exo-50%Endo) and 0.2% (25%Exo-75%Endo), respectively. Conclusions Assuming modest levels of endogenous boosting, the increase in HZ incidence following childhood varicella vaccination was smaller and lasted for a shorter period compared with 100%Exo-0%Endo boosting assumption. Endogenous boosting mechanism could partly explain the divergence between previous HZ-incidence projections and real-world evidence. Electronic supplementary material The online version of this article (10.1186/s12879-019-3759-z) contains supplementary material, which is available to authorized users.

Varicella, although a frequently benign childhood disease, nevertheless represents a considerable health burden. WHO recommends including varicella vaccines in universal routine vaccination programs, and maintaining coverage80%. Many countries have successfully introduced varicella vaccination and have benefited from lower disease burden, but many others have not adopted the vaccine. Reasons include cost commitment for a 'mild childhood disease' or concerns that vaccination will shift varicella to older age groups or increase herpes zoster incidence. Areas covered: This literature review summarizes the effectiveness and epidemiological impact of varicella immunization programs. Expert commentary: Varicella vaccines are immunogenic with acceptable safety profiles. One and two dose schedules are highly effective against varicella and large reductions in disease incidence, particularly moderate-severe disease, have been widely reported. There is currently no evidence to suggest that the introduction of varicella vaccination results in a shift of varicella disease burden to older age groups. Although epidemiological studies have shown an increased incidence of herpes zoster since the vaccines were launched, there are many other contributing factors, and indeed, this secular trend was evident before their introduction. In conclusion, varicella vaccination easily fits into existing immunization programs and significantly reduces the often underestimated burden of varicella.

Simvastatin, a cholesterol-lowering drug, is reported to have immunomodulatory properties that attenuated acute lung injury independent of their major lipid lowering effects. Based on these reports, simvastatin is expected to be used for influenza prophylaxis and treatment. The present study evaluated the efficacy of simvastatin against influenza A/PR/8/34 virus infection in a murine model. In a first study, simvastatin was administered orally. To achieve high plasma levels, intraperitoneal application was used in a second study. Survival, body weight loss, viral titers in lung and trachea, and histologic lung injury were measured. Surprisingly, treatment with simvastatin resulted in lower survival rates and in more distinct body mass loss in comparison to virus-infected control mice. Furthermore, the viral load in lungs and tracheas as well as histopathological lesions were not reduced by simvastatin. Overall, these results showed that simvastatin failed to protect mice against influenza virus infection. J Med. Virol. 85:1978–1982, 2013. © 2013 Wiley Periodicals, Inc.

Die Deutsche Vereinigung zur Bekampfung der Viruskrankheiten (DVV) e.V. und die Gesellschaft fur Virologie (GfV) e.V. geben nach unserem Wissen erstmalig in Europa konkrete Empfehlungen zum Einsatz von HIV-positiven Mitarbeiterinnen und Mitarbeitern im Gesundheitswesen. Grundsatzlich gelten fur HIV-positives medizinisches Personal klar definierte Auflagen. Bei einer dauerhaften Viruslast von ≤ 50 Kopien/ml konnen unter der Einhaltung der festgelegten Masnahmen (z. B. Tragen doppelter Handschuhe, regelmasige arbeitsmedizinische Betreuung, mindestens vierteljahrliche Kontrollen der HI-Viruslast, regelmasige Betreuung durch einen in der HIV-Therapie erfahrenen Arzt) von dem HIV-positiven medizinischen Beschaftigten alle operativen und invasiven Tatigkeiten durchgefuhrt werden. Die uneingeschrankte Tatigkeit des HIV-positiven medizinischen Beschaftigten ist jedoch nur dann moglich, wenn Adharenz bei der antiretroviralen Therapie besteht und wenn alle zur Vermeidung einer Infektionsubertragung erforderlichen Masnahmen regelrecht eingehalten werden. Unter Einhaltung der Vorgaben dieser Empfehlungen gehen von dem HIV-positiven medizinischen Beschaftigten mit an Sicherheit grenzender Wahrscheinlichkeit keine Gefahren fur Patienten aus.

Due to the increasing number of non-travel-associated hepatitis E virus (HEV) infections observed in several industrialised countries including Germany, there is a substantial interest in the characterisation of risk factors and transmission routes relevant to autochthonous HEV infections. Autochthonous cases are believed to be the result of a zoonotic HEV transmission from pigs, wild boars and deer. Recently, a high prevalence of HEV-specific antibodies in the German domestic pig population has been demonstrated. Thus, one may assume a higher prevalence of HEV-specific antibodies in humans with occupational exposure to pigs. In this study, sera obtained from 24 slaughterers, 14 meat inspectors, 46 pig farmers and 22 veterinarians were tested for the presence of HEV-specific antibodies using a line immunoassay. For comparison, sera obtained from 116 age- and gender-matched blood donors were also included. Twenty eight per cent (28.3%; 30/106) of the swine-exposed humans and 15.5% (18/116) of the blood donors without contact to pigs exhibited IgG-antibodies determined as reactive (i.e. borderline or positive) against HEV. Thus, an increased risk of HEV infection in humans occupationally exposed to pigs and particularly for slaughterers (41.7%; 10/24) was demonstrated.

This review explores the application of the Simplex representation of molecular structure (SiRMS) QSAR approach in antiviral research. We provide an introduction to and description of SiRMS, its application in antiviral research and future directions of development of the Simplex approach and the whole QSAR field. In the Simplex approach every molecule is represented as a system of different simplexes (tetratomic fragments with fixed composition, structure, chirality and symmetry). The main advantages of SiRMS are consideration of the different physical–chemical properties of atoms, high adequacy and good interpretability of models obtained and clear procedures for molecular design. The reliability of developed QSAR models as predictive virtual screening tools and their ability to serve as the basis of directed drug design was validated by subsequent synthetic and biological experiments. The SiRMS approach is realized as the complex of the computer program ‘HiT QSAR’, which is available on request.

Background Influenza is associated with substantial morbidity and mortality in pregnant women and neonates, but few countries offer annual influenza vaccination with the inactivated vaccine to all women who are, or intend to become, pregnant. Objectives To provide seroepidemiological information on influenza A and B antibodies in pregnant women and their offspring in Germany. Study design Anti-influenza antibodies were determined using commercially available enzyme-linked immunosorbent assays (ELISA) on serum obtained from 209 women and their newborns at delivery. Results The prevalence of antibodies against influenza A virus was 93.8% [89.6–96.6%] in the mothers and 96.7% [93.2–98.6%] in the newborns. The prevalence of antibodies against influenza B virus was 42.1% [35.3–49.1%] in the mothers and 78.5% [72.3–83.8%] in their newborns, which was a significant difference. The antibody concentrations against both influenza A and influenza B viruses were significantly lower in mother than in their newborns. Conclusions Because of active placental transport of IgG antibodies, neonates have higher prevalence and/or concentrations of influenza A and B virus-specific antibodies induced by natural infections than their mothers. Considering these serological findings, especially the lower prevalence of maternal antibody against influenza B virus, annual influenza vaccination may improve the protection of pregnant women and their offspring against influenza.

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.

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.

SUMMARYAcute parvovirus B19 infection is a risk for pregnant women. After vertical transmission the infected fetus may develop hydrops fetalis. Since B19 infection occurs mainly during childhood, children represent a main source for virus transmission. In order to determine whether certain groups in the German population show increased risks for B19 infection we analysed the seroprevalence using 6583 sera collected from adults in former Eastern and Western Germany during the German National Health Survey and 649 sera from healthy Thuringian children and adolescents. In adults the overall seroprevalence was 72·1%, rising from 20·4% in children (1–3 years) and 66·9% in adolescents (18–19 years) to 79·1% in the elderly (65–69 years). Significant differences were observed between females (73·3%) and males (70·9%) and between inhabitants of small (74·8%) and big cities (69·0%) but not between people of the former Eastern (72·8%) and Western states (72·0%) of Germany. For women during childbearing age (18–49 years) highest values were observed in those living together with two or more children (81·6%) and in women with occupational contact with children aged 6 years and adolescents (63·8%).

Former economic analyses have shown that universal mass vaccination of infants against varicella using a one-dose schedule is cost-saving in Germany. In July 2006, an MMRV combination vaccine has been approved in Germany which shall be given in a two-dose schedule. We re-analysed our former analysis with the EVITA model in order to prove whether our former conclusion that universal mass vaccination against varicella is cost-saving is still valid when using a two-dose schedule vaccine. Indeed we found that universal mass vaccination of infants against varicella with a two-dose vaccine is cost-saving from societal as well as from health care perspective.

ObjectiveRoutine influenza vaccination is currently recommended in several countries for people aged more than 60 or 65 years or with high risk of complications. A lower age threshold of 50 years has been recommended in the United States since 1999. To help policymakers consider whether such a policy should be adopted more widely, we conducted an economic evaluation of lowering the age limit for routine influenza vaccination to 50 years in Brazil, France, Germany, and Italy.MethodsThe probabilistic model was designed to compare in a single season the costs and clinical outcomes associated with two alternative vaccination policies for persons aged 50 to 64 years: reimbursement only for people at high risk of complications (current policy), and reimbursement for all individuals in this age group (proposed policy). Two perspectives were considered: third-party payer (TPP) and societal. Model inputs were obtained primarily from the published literature and validated through expert opinion. The historical distribution of annual influenza-like illness (ILI) incidence was used to simulate the uncertain incidence in any given season. We estimated gains in unadjusted and quality-adjusted life expectancy, and the cost per quality-adjusted life-year (QALY) gained. Deterministic and probabilistic sensitivity analyses were conducted.ResultsComparing the proposed to the current policy, the estimated mean costs per QALY gained were R$4,100, &U20AC;13,200, &U20AC;31,400 and &U20AC;15,700 for Brazil, France, Germany, and Italy, respectively, from a TPP perspective. From the societal perspective, the age-based policy is predicted to yield net cost savings in Germany and Italy, whereas the cost per QALY decreased to R$2800 for Brazil and &U20AC;8000 for France. The results were particularly sensitive to the ILI incidence rate, vaccine uptake, influenza fatality rate, and the costs of administering vaccination. Assuming a cost-effectiveness threshold ratio of &U20AC;50,000 per QALY gained, the probabilities of the new policy being cost-effective were 94% and 95% for France, 72% and near 100% for Germany, and 89% and 99% for Italy, from the TPP and societal perspectives, respectively.ConclusionExtending routine influenza vaccination to people more than 50 years of age is likely to be cost-effective in all four countries studied.

Varizellen (Windpocken) gehoren zu den haufigsten impfpraventablen Erkrankungen in Deutschland. Wahrend der Schwangerschaft kann die Erkrankung zu schweren Folgen fur die Schwangere selbst sowie fur den Fetus bzw. das Neugeborene fuhren. Fur schwangere Frauen ist das Risiko fur eine Varizellenpneumonie, die als medizinischer Notfall anzusehen ist, erhoht. Zwischen der 5. und 24. Schwangerschaftswoche konnen Windpocken zum fetalen Varizellensyndrom fuhren. Bei einer mutterlichen Erkrankung in den letzten Schwangerschaftswochen oder kurz nach der Entbindung kann der Erreger Varizellen des Neugeborenen hervorrufen. Geschieht dies in einem Zeitraum von 5 Tagen vor bis zu 2 Tagen nach der Geburt, ist mit lebensbedrohlichen disseminierten neonatalen Varizellen zu rechnen. Mit den derzeit zur Verfugung stehenden diagnostischen, immunprophylaktischen und therapeutischen Masnahmen besteht die Moglichkeit, diese schwerwiegenden Folgen von Varizellen wahrend der Graviditat zu verhindern.

Varicella during pregnancy can be associated with severe illnesses for both the mother and her neonate. Varicella pneumonia must be regarded as a medical emergency, since pregnant women are at risk of life-threatening ventilatory compromise and death. After maternal chickenpox in the first and second trimesters, congenital varicella syndrome may occur in nearly 2% of the cases. The characteristic symptoms consist of skin lesions in dermatomal distribution, neurological defects, eye diseases and skeletal anomalies. If the mother develops varicella rashes between day 4 (5) antepartum and day 2 postpartum, generalized neonatal varicella leading to death in about 20% of the cases has to be expected. Normal zoster has not been shown to be associated with maternal pneumonia, birth defects or problems in the perinatal period. On the basis of the clinical consequences of varicella-zoster virus infections during pregnancy, the present paper summarizes the currently available concepts of prevention, diagnosis and therapy.

Antiviral drugs are a valuable supplementation to vaccines for the control and prevention of influenza. In Germany, for treating influenza amantadine, oseltamivir and zanamivir are approved. Amantadine and oseltamivir are also licensed for prophylactic use. On behalf of the Paul-Ehrlich-Society of Germany and the German Association for the Control of Virus Diseases, as two independent scientific societies, the first consensus Conference on the Antiviral Treatment and Prophylaxis of Influenza was held in June 2002. Based on the available data of clinical studies an expert group developed the following recommendations for the appropriate clinical use of the antiviral drugs: (1) since oseltamivir (orally administered) and zanamivir (administered by inhalation) have apparently similar clinical efficacy both drugs can be used alternatively for treatment. (2) Amantadine is not an alternative to the neuraminidase (NA) inhibitors because it is not effective against influenza B viruses, it frequently selects resistant virus mutants and it can cause adverse events. (3) When influenza is prevalent in the community patients with the clinical diagnosis of influenza should be treated with neuraminidase inhibitors if the symptoms are lasting not longer than 48 h. (4) Immunocompetent patients with a non-febrile illness and patients with a symptom history of more than 2 days should not be treated with antiviral drugs. (5) Although there are no data from clinical trials immunocompromised patients should also be treated when influenza has been diagnosed. (6) The prophylactic use of antiviral drugs can be recommended for persons with close contact to acutely ill persons and no recent vaccination against influenza. (7) The use of anti-influenza drugs have to be considered for prophylaxis in pandemics. A precondition for the adequate use of anti-influenza drugs in the primary medical care is the timely information on the local influenza situation delivered by surveillance systems.

The neuraminidase inhibitors (NI) Oseltamivir and Zanamivir are a valuable supplementation to vaccines for the control and prevention of influenza. To support the appropriate clinical use of these new antiviral drugs, guidelines have been developed in Germany. A prerequisite for an accurate clinical diagnosis is that the physicians obtain actual information on the epidemic situation, particularly in their region. Reliable, real-time information can be provided by the newly developed surveillance system, RealFlu™. The results of an evaluation of 99 NI-treated influenza patients and their medical laboratory values are presented.

As epidemiological data concerning varicella in Germany were not available, a retrospective study was conducted to investigate the impact of the disease, focusing also on economic aspects. A representative German-wide sample of 1334 unvaccinated varicella cases was obtained in 1999 from randomly selected paediatric (P) and general, as well as internal, mainly adult (A), practices. Following representative weighting, the median age was 5 years, with 90% of cases aged < 12 years. The highest incidence was in children aged 5–6 years. Varicella-related complications occurred in 5.7% of patients, and accounted for 0.1 hospital days/case on average. Certificates of sick leave were issued for 1.3 sick days/case, with 0.6 days paid by health insurance funds to parents caring for their sick child, and 0.7 days paid by the employer. With an annual incidence of 760 000 diagnosed cases in Germany for the year 1999, this amounts to an annual cost of c.150 million Euro, with c. 50 million Euro paid by the statutory health insurance system. It was concluded that universal varicella vaccination in Germany would provide essential clinical improvements for patients and prevent hospital admissions. In addition, significant economic benefits can be expected, mainly because of the high level of indirect health costs in Germany.

Universal varicella vaccination of infants in Germany was shown to be effective and cost-saving by the EVITA-model (Economic Varicella VaccInation Tool for Analysis).[1] However, affordability proves to be a “fourth hurdle”. The objective of this study is to examine budget impacts of universal varicella vaccination from a payer’s (sickness funds’) perspective. The validated, dynamic infections disease model EVITA was used to analyse budget impacts over 30 years. Universal vaccination of children in their second life year was compared to the currently recommended risk-group strategy. In the USA, universal varicella vaccination was implemented in 1996. Based on US-experience, three scenarios for the development of the coverage rates have been estimated. The price level of 2002 was used. Future costs were not discounted to show the full budget impact in future years. Aspects concerning the incidence of herpes zoster have not been included in the analysis. Under the current risk-group strategy, an annual average of 721,400 cases, 38,700 complications and 5,500 hospitalisations occur in Germany. Annual varicella costs for sickness funds amount to 73 million €, 50 % thereof due to sick-leave costs of parents staying at home to care for their sick child covered by sickness funds. Other costs relate to hospitalisations (24 %), physician services (12 %), medication (11 %) and vaccination (3 %). With a universal vaccination strategy, morbidity is on average reduced by 75 % to 80 % (this and the following results depend on the analysed scenario). Vaccination costs rise to a maximum of 42–43 million € p. a. within about 10–12 years and therefore account — at maximum — for about 0.03 % of the total payers’ health care budget. Other varicella costs however decrease by more than 80 % in the same time. Overall varicella costs rise by 8 % to 13 % in the first few years because of the additional investment in vaccination. In the 6th to 8th year, however, savings in treatment and work loss costs compensate vaccination costs, leading to net savings. Over 30 years, average annual varicella costs decrease by 31 % to 33 % to a level between 49 and 51 million €. Sensitivity analyses showed only marginal variations in these results with maximum coverage rate, price of vaccine, and work loss costs being the most influential variables. Under the current risk-group vaccination strategy, varicella causes a high burden of disease resulting in considerable utilisation of health care resources and related costs. Universal vaccination can effectively reduce morbidity and utilisation. This strategy has a small impact on overall health care costs. For a short time, investment in varicella vaccination causes additional costs, which are low compared to current annual varicella costs, and does not influence sickness funds’ premiums. Reduced morbidity rapidly leads to savings and significant net-savings occur in 6–8 years.

Varicella (chickenpox) has traditionally been regarded as a benign, inevitable disease of childhood. In Germany information on the clinical and economic impact of varicella is limited. This study assessed the health risks and economic burden of varicella with a special focus on the relevance of complications as a cost driver. We used an age-structured, dynamic infectious disease model for the spread of infection in the German population combined with a module modeling the course of disease and medical management in the case of infection. Model input data were derived mainly from a retrospective epidemiological survey of 1,334 varicella cases in Germany. This survey included detailed information on outpatient care, complications, inpatient treatment, and sick leave. In the base case analysis the model predicted approx. 740,000 varicella cases per year. Some 40,000 experienced complications, of which 5,700 required inpatient care. Total annual costs for payers, i.e., sickness funds, was 78 million euro, the largest portion of which was due to the significant coverage of work loss costs incurred by parents caring for their sick children ("Kinderpflegekrankengeld"). For the society total annual costs were 187.5 million euro, 82% of which was indirect. Complications account for disproportionate 32% (25%) of cost from the payers' (societal) perspective. However, the vast majority of costs are due to uncomplicated cases. The burden of varicella in Germany is thus significant, not only in terms of morbidity but also from an economic viewpoint. Vaccination strategies targeting groups with high risk of complications might fail to reduce the considerable burden of varicella substantially. Routine vaccination against varicella would be a meaningful measure to reduce the burden of VZV infection in Germany.

Seit 1990 hat sich in den neuen Bundeslandern das Alter erstgebarender Frauen deutlich erhoht, was Veranderungen des Antikorperschutzes bei den Schwangeren und ihren Neugeborenen zur Folge haben konnte. Aufgabe der vorliegenden Studie war es, die Antikorper bei schwangeren Frauen und deren Neugeborenen gegen impfpraventable virale Infektionen zu bestimmen, um Ruckschlusse auf den Schutz vor diesen Erkrankungen ziehen zu konnen. Zu diesem Zweck erfolgte bei 290 schwangeren Frauen der neuen Bundeslander mit einem Durchschnittsalter von 28 Jahren und bei deren Neugeborenen die Bestimmung der Antikorper gegenuber Masern, Mumps, Roteln, Poliomyelitis und Varizellen. Die Ergebnisse zeigten, dass die schwangeren Frauen zu 79% Antikorper gegen Masernvirus, zu 96% gegen Mumpsvirus, zu 87% gegen Rotelnvirus, zu 62–64% gegen Poliomyelitisvirus Typen 1–3 und zu 97% gegen das Varicella-Zoster-Virus (VZV) aufwiesen. Vergleichende Untersuchungen zur Seropravalenz der Antikorper bei Neugeborenen ergaben keine signifikant differenten Befunde. Wurden die Antikorpertiter von Muttern und Kindern verglichen, so waren im Nabelschnurblut der Neugeborenen signifikant hohere Antikorpertiter gegen das VZV nachweisbar. Zusammenfassend ist festzustellen, dass die Pravalenz von Antikorpern gegen Masern und Poliomyelitis wahrscheinlich nicht ausreicht, um Neugeborene effizient zu schutzen. Eine mutterliche Immunitatslucke gegenuber Roteln von 13% birgt fur die Neugeborenen eine potenzielle Gefahr, an einem kongenitalen Rotelnsyndrom zu erkranken. Trotz der hohen Seropravalenz von Antikorpern gegen Varizellen besteht ein nicht zu unterschatzendes Potenzial fur Infektionen wahrend Schwangerschaft und Neonatalperiode.

The risk of developing malignant cutaneous neoplasms is increased after organ transplantation. We report three patients with malignant tumors of the epithelium of the facial skin and the lips after kidney and heart transplantation, respectively. They showed an aggressive course of the disease with more than five synchronous or metachronous basal cell and squamous cell carcinomas. Tissue samples were Epstein-Barr virus (EBV) positive by PCR. Using an in situ hybridization technique EBV-encoded RNA (EBER) was detected in tumor-infiltrating lymphocytes. The aggressive course was not alone controllable by surgical or radiological therapy. The systemic and topical application of cidofovir (Vistide) led to remarkable remissions, to a better confinement and operability of the tumors, and to a cessation of tumor pain. The photodynamic therapy represents another opportunity for managing superficial local recurrences and multiple tumors. In conclusion, the results of these case reports demonstrate that combined antiviral, photodynamic and surgical therapy may be used successfully to treat aggressive cutaneous malignancies in patients after organ transplantation.

Brivudin [(E)-5-(2-bromovinyl)-2'-deoxyuridine] is a nucleoside analogue with a high and selective antiviral activity against varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1). The double-blind, randomized study presented here compared efficacy and safety of oral brivudin 1 x 125 mg and acyclovir 5 x 800 mg, both for 7 days, in 1227 immunocompetent patients with herpes zoster. Main results were as follows: brivudin was superior to acyclovir in accelerating the "time to last formation of new vesicles" (primary parameter; risk ratio(ITT): 1.13, P=0.014). Equivalent effects of brivudin and acyclovir were observed for the secondary parameters "time to first crust" (RR(ITT): 0.93, P=0.004), "time to full crusting" (risk ratio(ITT): 1.03, P0.001), and "time to loss of crusts" (RR(ITT): 0.95, P=0.002). The incidence of potentially treatment-related adverse events was similar under brivudin (7.7%) and acyclovir (10.0%). In conclusion, brivudin proved to be more effective than acyclovir in terminating vesicle formation, the parameter which reflects the end of viral replication, thus confirming, in the clinical setting, the greater in vitro antiviral activity of brivudin. Compared with acyclovir, brivudin provides a similar safety profile and a significant improvement in efficacy.

Varicella zoster virus (VZV) causes varicella (chickenpox), remains dormant in dorsal root and cranial nerve ganglia and can be reactivated as a consequence of declining VZV-specific cellular immunity leading to herpes zoster (shingles). Patients older than 50 years of age affected by herpes zoster may suffer a significant decrease of quality of life. These patients and immunocompromised individuals are at increased risks for severe complications, involving the eye, the peripheral and the central nervous system (prolonged pain, postherpetic neuralgia). Such complications occur with and without cutaneous symptoms. The German Dermatology Society (DDG) has released guidelines in order to guarantee updated management to anyone affected by herpes zoster. Diagnosis is primarily clinical. The gold standard of laboratory diagnosis comprises PCR and direct identification of VZV in cell cultures. Detection of IgM- and IgA-anti VZV antibodies may be helpful in immunocompromised patients. Therapy has become very effective in the last years. Systemic antiviral therapy is able to shorten the healing process of acute herpes zoster, to prevent or to alleviate pain and other acute and chronic complications, particularly, when given within 48 h to a maximum of 72 h after onset of the rash. Systemic antiviral therapy is urgently indicated in patients beyond the age of 50 years and in patients at any age with herpes zoster in the head and neck area, especially in patients with zoster ophthalmicus. Further urgent indications are severe herpes zoster on the trunk and on the extremities, herpes zoster in immunosuppressed patients and in patients with severe atopic dermatitis and severe ekzema. Only relative indications for antiviral therapy exist in patients younger than 50 years with zoster on the trunk and on the extremities. In Germany acyclovir, valacyclovir, famciclovir and brivudin are approved for the systemic antiviral treatment of herpes zoster. These compounds are all well tolerated by the patients and do not differ with regard to efficacy and safety. Brivudin has a markedly higher anti-VZV potency than oral acyclovir, valacyclovir and famciclovir and thus offers a simpler dosing regimen. It must be given only once daily during 7 days in comparison to three and five times dosing per day of valacyclovir, famciclovir and acyclovir, respectively. Brivudin is an antiviral agent with no nephrotoxic properties, which is an advantage when compared to acyclovir. The most important aim of therapy of herpes zoster is to achieve painlessness. Appropriately dosed analgesics in combination with a neuroactive agent (i.e. amitriptylin) are very helpful when given together with antiviral therapy. The additive therapy with corticosteroids may shorten the degree and duration of acute zoster pain, but has no essential effect on the development of postherpetic neuralgia, which is a very difficult condition to treat. Thus early presentation to a pain therapist is recommended in specific cases.

This study explores the economic value of a routine varicella vaccination program for Germany. An age-structured decision analytic model was used to assess the benefits, costs and cost-effectiveness of an immunization program for a period of 30 years. Three interventions were compared with no vaccination: universal vaccination of around 15 months old healthy children, vaccination of susceptible adolescents (11-12 years of age), and the combined strategy. The analysis was conducted from both the societal perspective and the payers', i.e. sickness funds, perspective. Input data were mainly derived from a retrospective survey (analyzed were 1334 patient records) and from a seroprevalence study (n = 4602 sera). Using a coverage rate of 85% and a vaccine efficacy rate of 86% routine children vaccination could prevent around 611,000 varicella cases and over 4700 major complications per year. Average yearly cost savings for the society are 51.3 million Euro. The benefit-cost ratio (BCR) is 4.12. From the third-party payer's perspective, the BCR is 1.75 which is a consequence of significant reimbursement of parent's lost earnings by German sickness funds. The adolescent vaccination strategy has a favorable BCR ratio of 8.44 from the societal perspective, but clearly inferior medical effects. The combined vaccination strategy showed similar results as the children strategy. Routine childhood varicella vaccination appears to be a highly efficient strategy to reduce the burden of varicella and results in significant savings for both the society and the payers.

Varicella is a potentially serious infection not only in immunocompromised individuals but also in otherwise healthy adults and children. Vaccination plays an important role in preventing the disease and its sequelae. A universal vaccination in childhood is expected to reduce substantially the number of uncomplicated cases of varicella and decrease the number of complicated cases requiring hospitalisation. To generate data as basis for decisions of the health authorities concerning prevention of varicella, epidemiological and health-economic data were collected in two studies. Using an age-structured decision analytic model the benefits, costs and cost effectiveness of a varicella immunisation program for a period of 30 years were assessed. It was shown that after the first year of life seroprevalence rates increased steadily and reached 62% among the 4- to 5-year olds and 94% among the 10- to 11-year olds, respectively; 90% of varicella patients were younger than 12 years. A severe course was assessed for 16.3% of the cases. Overall incidence of complications was estimated to be 5.7%. A routine varicella vaccination program targeting healthy children could prevent 82.7% of varicella cases and over 4,700 major complications per year provided the coverage level was 85%. Under these conditions the elimination of varicella is predicted to be achievable within 18 years. It is expected that a combined measles, mumps, rubella and varicella vaccine could provide the required coverage. Average yearly discounted net cost savings of universal childhood vaccination are 51 million Euro with a benefit-cost ratio of 4.12. Childhood vaccination with catch-up of adolescents provides additional clinical benefits. The break-even point indicating first net savings could be achieved already 3 years after the implementation of the vaccination program. In summary, routine childhood varicella vaccination appears to be a highly efficient strategy to significantly reduce the sizeable burden of varicella and would lead to net savings from both the societal but also the payer perspective.

Hintergrund: Das Herpes zoster wird meist klinisch diagnostiziert. Bei atypischen Verlaufen ist eine virologische Diagnostik erforderlich, die aufgrund guter therapeutischer Moglichkeiten rasch und zuverlassig erfolgen sollte. Patienten und Methodik: Die derzeit am haufigsten eingesetzten Methoden, wie Virusantigendirektnachweis, Virusisolierung und Serologie, wurden hinsichtlich ihrer Aussagekraft und Praktikabilitat mit der Polymerasekettenreaktion (PCR) bei 100 Patienten mit Zoster verglichen. Ergebnisse: Mit der PCR unter Einbeziehung von Oligonukleotiden der offenen Leserahmen 28 und 29 des Varicella-Zoster-Virus-(VZV-)Genoms konnte eine Sensitivitat von 94% bei einer Spezifitat von 100% erreicht werden. Der innerhalb kurzer Zeit durchfuhrbare Antigendirektnachweis zeigte eine Empfindlichkeit von 82% und eine Spezifitat von 70%, was jedoch nur bei 71% der Patienten zu einem aussagefahigen Ergebnis fuhrte. Allein auf der Basis serologischer Parameter war lediglich bei 61% der Patienten eine aktive VZV-Infektion nachzuweisen. Die haufig als “Goldstandard” angesehene Virusanzucht gelang nur bei 20%, wobei die Ergebnisse eine starke Abhangigkeit vom Zeitpunkt der Materialentnahme und der Immunkompetenz der Patienten zeigten. Schlussfolgerungen: Die PCR sollte in der Routinediagnostik als Methode der Wahl zur Diagnostik des Zosters bei atypischen Verlaufen eingesetzt wrden. Serologische Methoden sind nur zur retrospektiven Diagnosesicherung zu empfehlen.

Maternal varicella during the first two trimesters of pregnancy may cause the congenital varicella syndrome (CVS). After infection in the first 20 weeks' gestation, the incidence is estimated to be about 2%. To date, nearly 100 infants born with signs of CVS have been reported in the literature, more than three quarters of them during the last two decades. The characteristic symptoms consist of skin lesions in dermatomal distribution (76%), neurologic defects (60%), eye diseases (51%), and skeletal anomalies (49%). About 30% of infants born with these lesions died in the first months of life. The diagnosis of CVS should be established by the appearance of maternal varicella, the presence of typical clinical symptoms as well as the laboratory evidence of in utero varicella-zoster virus (VZV) infection. In the reviewed infants, intrauterine VZV-infection has been proved in about 60%. Passive immunization may reduce the risk of fetal infection but there is no evidence to prevent fetal viremia. Up to now, there are no controlled studies concerning antiviral chemotherapy in preventing CVS.

Influenza viruses type A and B can cause a wide spectrum of illness, and they are responsible for considerable mortality and morbidity. With the new neuraminidase inhibitors, of which zanamivir was the first drug to be licensed, the physician has antivirals at his disposal which are safe and effective against both influenza virus type A and type B. Available data from clinical Phase III studies indicate benefits in terms of a reduction in the median time to alleviation of major symptoms by 1.5 to 3 days when treatment is started within 36 to 48 h after onset of influenza. Similar results have been obtained with oseltamivir. Neuraminidase inhibitors provide a valuable treatment option, particularly for individuals not protected by vaccination, and those at high risk of influenza-related complications. The study results obtained so far indicate that patients with pre-existing diseases and those with severe influenza symptoms profit most from the treatment. This is confimed by our own experience in treating severe influenza conditions.

This study was carried out to determine the prevalence of antibodies to herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) in selected German populations, such as blood donors, hospital patients, and human immunodeficiency virus (HIV)-seropositive individuals. Serum samples collected between 1996 and 1998 were tested by enzyme immunoassays using monoclonal antibody-selected native gG1 and gG2 as antigens and an immunoblot using type-specific recombinant glycoproteins. Equivocal results were resolved by an "in-house" Western blot assay. The prevalence of HSV-1 antibodies increased steadily with age and reached high levels of >/=88% among subjects 40 years of age or older. In the sample of patients and blood donors, the HSV-2 seroprevalence was 12.8% (95% CI = 11.9-13.8%). About 81% of the HSV-2 seropositive subjects were coinfected with HSV-1. When adjusted for age, there was no difference in the HSV-2 seroprevalence between hospital patients and blood donors. The HSV-2 seroprevalence was significantly higher among women (15%) than among men (10.5%), yielding a female : male odds ratio of 1.5 for hospital patients and of 1.67 for blood donors. Among the HIV-infected population, 91.1% were seropositive for HSV-1 and 47.9% for HSV-2. HIV-infected women have a significantly higher risk of HSV-2 infection than men (odds ratio [OR] = 3.22; 95% confidence ratio [CI] 1.99-5.20). In conclusion, although the rate of infections with HSV-2 is relatively low in the German population, attention should be given to the further development in adolescents, especially in view of a possible decrease of HSV-1 seroprevalence in childhood.

Diagnosis of herpes zoster needs to be rapid when effective antiviral chemotherapy is being considered. Patients with atypical clinical features can often only be diagnosed by virological methods. In the present study, vesicle specimens of 100 patients with zoster were analysed by detecting viral DNA using polymerase chain reaction (PCR). The findings were compared with those obtained by traditional virological and serological methods. PCR results confirmed the clinical diagnosis of zoster in 95%. Primers selected from varicella-zoster virus (VZV) gene 28 proved to be most sensitive. The sensitivity of virus culture was 20% (specificity 100%) and of direct immunofluorescent VZV-specific antigen staining in vesicle samples 82% (specificity 76%). There was a serological response to specific IgM and IgA antibodies in 48% within four days after the onset of rash. These findings suggest that PCR is the method of choice for rapid laboratory diagnosis of zoster.

Neoplasias associated with anogenital human papilloma viruses (HPV) are characterised by high patient morbidity and mortality and by appreciable limitations in the patientʼs quality of life. Each year 530,000 women worldwide and 4800 women in Germany develop cervical cancer 1, 2. Biomolecular and epidemiological studies carried out in the past 25 years have demonstrated causal link between persisting infections with HPV 16 and HPV 18 and at least 11 other so-called high-risk HPVs (HR-HPVs) and the development of cervical cancer and its precursor lesions (so-called dysplasias or, respectively, cervical intraepithelial neoplasias – CIN). HPV 16, HPV 18 and other HR-HPVs are also the causes of other cancers and their precursors, for example, vulvar, vaginal, penile and anal cancers as well as tonsillar and throat cancers and certain forms of skin cancer. So-called low-risk HPVs (LR-HPVs) such as HPV 6 and HPV 11 are responsible for over 90 % of anogenital condylomata acuminata (anogenital warts). Condylomata acuminata are the most common viral sexually transmitted disease (STD) worldwide 3. It is estimated that around 1 % of European and German populations (aged 15–49 years) have these benign but often very unpleasant tumours. The development of a prophylactic quadrivalent vaccine (HPV 6, 11, 16, 18) and a bivalent vaccine (HPV 16, 18) has made it possible to prevent infections of the cervical epithelium and other squamous epithelia and the development of precancerous lesions. In the case of the quadrivalent vaccine (HPV 6, 11, 16, 18), the development of condylomata acuminata can also be prevented. The Standing Committee on Immunisation of the Robert Koch Institute (STIKO) has published a recommendation on HPV vaccination. Based on data from studies on the efficacy of HPV vaccines for the prevention of precancerous lesions of the cervix, vagina, and vulva, the STIKO recommends immunisation for girls aged between 12 and 17 years. The current guidelines do not contradict this recommendation but rather provide a more comprehensive supplement. The S3 guidelines focus on prophylactic vaccination against HPV-16 and HPV-18 or, respectively, HPV-6 and HPV-11 infections and thus on the prevention of cervical, vulvar, vaginal, anal and penile cancer and their precursors as well as on the primary prevention of condylomata acuminata and laryngeal papillomas. This S3 guideline thus clearly differs from other guidelines such as the S1 guideline “Condylomata acuminata and other HPV-associated clinical entities of the genitals, anus and urethra” (Guideline of the German STI Society in cooperation with the German Dermatological Society and the Paul-Ehrlich Society) and the S2 guideline of the German Society for Gynaecology and Obstetrics “Prevention, diagnostics and therapy for HPV infections and HPV-associated pre-invasive lesions in gynaecology and obstetrics”. After the debate on HPV immunisation has been concluded, the S3 guideline for the prevention of cervical cancer issued by the German Society for Gynaecology and Obstetrics will follow the recommendations in the current guideline, which will be updated. The development process and most important contents of the guideline are briefly described below. The long version of the guideline gives a more detailed account (www.awmf.org).

The animal model of necrotic hepatitis caused by HSV-1 infection in juvenile mice was used to compare the efficacies of the oral antiherpes agents famciclovir (FCV), valaciclovir (VACV) and brivudin (BVDU). The experimental infection allows the measurement of viral replication in the liver by macroscopic lesions and the evaluation of mortality from encephalitis. Mice intravenously inoculated with a highly virulent clinical HSV-1 isolate were orally treated by gavage over a period of 3 days starting on day 2 post infection. The reference drug acyclovir (ACV) was administered subcutaneously. Necrotic hepatitis was significantly (p < 0.01) reduced by treatment with FCV, VACV and ACV at a dose of 50 mg/kg per day divided into 3 doses. No significant effect was achieved with BVDU at 200 mg/kg per day. Treatment with FCV at 50 mg/kg per day, ACV at 100 mg/kg per day, and VACV at 200 mg/kg per day significantly (p < 0.001) decreased mortality in mice. BVDU treatment at 200 mg/kg per day did not reduce mortality but significantly prolonged (p < 0.05) the survival time.

Seasonal influenza vaccination is recommended in Germany as a standard procedure for all persons aged 60 and above. Moreover, vaccination is also recommended for all persons at elevated risk of serious disease, for pregnant women, and for persons exposed to a higher than usual risk of infection (e1). In April 2012, the Strategic Advisory Group of Experts (SAGE) on Immunization of the World Health Organization (WHO) recommended the extension of national vaccination recommendations to children aged 6 to 59 months. Thus, the spectrum of target groups ranges from infants to very old persons, and from healthy persons with intact immune systems to the chronically ill. There is a corresponding variety in the tasks that influenza vaccines are required to fulfill. For example, a naive immune system that has never yet been in contact with influenza virus antigens cannot be effectively stimulated by the highly purified antigens contained in conventional influenza vaccines. The generation of robust immunity after primary vaccination requires a suitable vaccine, for example, one with added adjuvant or one containing live, attenuated virus (1). The elderly have a less effective immune system that has become accustomed to influenza virus antigens through decades of exposure to naturally occurring viruses and repeated immunizations. They therefore need a strong, age-specific immunologic stimulus to achieve lasting protection against disease due to infection with currently circulating influenza viruses. The same is true of influenza vaccines for the chronically ill. A number of influenza vaccines with improved immunogenicity have been approved in the last few years, and others are currently being clinically tested. In this article, we present the clinically relevant differences between conventional and newer influenza vaccines for each of the target groups in which they are used, and we discuss their optimal application.

Two-dose varicella vaccination is recommended for optimal control of varicella in populations with high (90%) 1-dose coverage. Optimal timing of the second dose may depend on whether breakthrough varicella results from primary vaccine failure (no protective immunity after vaccination) or secondary vaccine failure (waning protective immunity).Published literature (1995 to 2012) on vaccine failure after varicella vaccination cited in PubMed and other online sources was reviewed.Nineteen publications detailed 21 varicella outbreaks with breakthrough varicella rates ranging from 0% to 42%; the publications showed no consistent trend between breakthrough varicella rate and time since vaccination.Literature to date indicates a relatively high rate of primary vaccine failure and limited evidence of secondary vaccine failure among 1-dose varicella vaccine recipients, suggesting that a short interval between 2 doses might be preferable in countries considering implementation of universal varicella vaccination to reduce breakthrough varicella. However, any potential disruption to well-established vaccination schedules should be considered.

The efficacy of oral brivudin vs. intravenous acyclovir was compared in a randomized multicentered study under double-blind conditions using the double-dummy technique. Forty-eight patients with a herpes zoster rash less than 72 hours in duration were entered in the study. Brivudin was given as one 125-mg tablet every 6 hours. Acyclovir was infused over 1 hour at a dose of 10 mg/kg every 8 hours. Treatment was continued for 5 days. There was no significant difference between the treatment groups when analyzed in terms of new lesion formation, increase in the area of rash within the primary dermatome, cutaneous dissemination, and affection of mucous membranes or visceral organs. Both treatment regimes were also equally effective in the time to full crusting of lesions. Oral brivudin and intravenous acyclovir were well tolerated by most patients. There was no need to interrupt the treatment in any case. As effective as intravenous acyclovir in the treatment of herpes zoster, oral brivudin offers the potential for outpatient treatment of herpes zoster in immunocompromised patients.