[Vaccination in old age: an overview]. / Impfen im Alter: eine Übersicht.

Vaccinations against infectious diseases are a highly effective preventive measure, especially in old age due to the higher susceptibility to infections. As the effectiveness of vaccinations decreases in old age due to immune senescence but also due to comorbidities, specific, more immunogenic vaccines have been developed for this target group. In Germany, the Standing Commission on Vaccination (STIKO) publishes annually updated vaccination recommendations also specifically for the 60+ years age group. Since 2018, standard vaccinations for this group have included herpes zoster vaccination with adjuvanted inactivated vaccine. Since 2021, the use of the quadrivalent influenza high-dose vaccine is recommended for this age group. Currently, the annual COVID-19 vaccination and the single pneumococcal vaccination with the new 20-valent conjugate vaccine have been added as standard vaccinations. The free STIKO app provides an always up to date overview of standard and indicated vaccinations for all age groups.

[Influenza]. / Influenza.

Influenza is the infectious disease with the highest population-based mortality. It mainly affects those aged 60 years and older, mainly due to immune senescence, which also favors complicated courses and compromises vaccine effectiveness. Therefore, various approaches have been developed for more immunogenic vaccines, which are now available for use. The Ständige Impfkommission (STIKO) has taken this into account in its current recommendation on influenza vaccination and has recommended a quadrivalent, inactivated high-dose vaccine as the standard vaccine for all ≥ 60-year-olds. Despite these successes, vaccination for prevention remains underutilized. Germany has never reached the WHO vaccination target of 75% of the elderly population. The main reasons for this are a lack of confidence in the effectiveness of vaccination, a lack of/restricted risk perception of the disease, and barriers to implementation. Initial approaches to overcoming these barriers, such as low-threshold vaccination services by involving pharmacies, are being implemented. However, further steps are needed to realize the potential of influenza vaccination, especially for such vulnerable groups as older adults.

Screening for common eye diseases in the elderly with Optos ultra-wide-field scanning laser ophthalmoscopy: a pilot study with focus on ocular toxoplasmosis.

PURPOSE: Studies on the occurrence of ocular toxoplasmosis (OT) in a general population are rare. Therefore, we conducted this pilot study to assess whether a nonmydriatic ultra-wide-field (UWF) scanning laser ophthalmoscope (SLO) is suitable for a simple, rapid screening procedure. METHODS: The population of this cross-sectional study was randomly recruited from a cohort of hospital-based patients in an urban geriatric hospital. Ophthalmologic evaluation was performed on 201 eyes from 101 participants through nonmydriatic UWF-SLO (Optos Daytona) and assessed for suspicious lesions and other relevant ocular findings. All images were evaluated by two independent examiners. Individuals who presented lesions with a morphological appearance suggestive of OT underwent fundoscopy and serological analysis of Toxoplasma gondii-specific antibodies. RESULTS: The mean age of the study group was 76 years, and 63 (62%) were female. Despite many health restrictions, the SLO examination was carried out easily in this geriatric population. Three participants presented findings by SLO suspicious for T. gondii-related injury. Further clinical examination and serological investigation confirmed the diagnosis, with funduscopic evaluation and positive T. gondii ELISA testing. In addition, a high rate of arterial hypertension and dyslipidemias within the cohort led to a high incidence of vascular changes and age-related fundus findings. CONCLUSION: In our study, we confirm that UWF-SLO technology is helpful in the rapid detection of peripheral retinal injuries in elderly patients such as OT and may be used as a routine screening tool.

[Vaccination in older adults: compulsory or voluntary exercise?] / Impfen im Alter ­ Pflicht oder Kür?

BACKGROUND: Immunosenescence leads to an increasing susceptibility to infections. Therefore, vaccination is an essential element of prevention. The recommendations of the permanent vaccination commission (STIKO), a committee at the Robert-Koch-Institute, affiliated to the German Government, are updated every year and include a particular section dealing with older adults. CURRENT DEVELOPMENTS: Immunosenescence reduces vaccine effectiveness. Thus, older adults and patients with multimorbidity are in need of more immunogenic vaccines. Cell culture derived quadrivalent influenza vaccine, trivalent adjuvanted vaccine and a high dose influenza vaccine show higher immune response in these groups. STIKO actually recommends an adjuvanted herpes zoster subunit vaccine to all adults in the age of 60 and above because of its vaccine effectiveness of 90 % in all age groups. The increasing travel activities of older adults require travel vaccination advice that takes into account travel destination as well as multimorbidity. Adjusted vaccination schedules and controlling of antibody titers have to be considered. OUTLOOK: New vaccines are under development, that are more immunogenic and therefore more effective (e. g. pneumococcal vaccine) or that prevent infections for which a vaccine was previously not available (e. g. norovirus vaccine).

Higher serum levels of fibroblast growth factor 21 in old patients with cachexia.

OBJECTIVE: Fibroblast growth factor (FGF)21 is promptly induced by short fasting in animal models to regulate glucose and fat metabolism. Data on FGF21 in humans are inconsistent and FGF21 has not yet been investigated in old patients with cachexia, a complex syndrome characterized by inflammation and weight loss. The aim of this study was to explore the association of FGF21 with cachexia in old patients compared with their healthy counterparts. METHODS: Serum FGF21 and its inactivating enzyme fibroblast activation protein (FAP)-α were measured with enzyme-linked immunoassays. Cachexia was defined as ≥5% weight loss in the previous 3 mo and concurrent anorexia (Council on Nutrition appetite questionnaire). RESULTS: We included 103 patients with and without cachexia (76.9 ± 5.2 y of age) and 56 healthy controls (72.9 ± 5.9 y of age). Cachexia was present in 16.5% of patients. These patients had significantly higher total FGF21 levels than controls (952.1 ± 821.3 versus 525.2 ± 560.3 pg/mL; P = 0.012) and the lowest FGF21 levels (293.3 ± 150.9 pg/mL) were found in the control group (global P < 0.001). Although FAP-α did not differ between the three groups (global P = 0.082), bioactive FGF21 was significantly higher in patients with cachexia (global P = 0.002). Risk factor-adjusted regression analyses revealed a significant association between cachexia and total (ß = 649.745 pg/mL; P < 0.001) and bioactive FGF21 (ß = 393.200 pg/mL; P <0.001), independent of sex, age, and body mass index. CONCLUSIONS: Patients with cachexia exhibited the highest FGF21 levels. Clarification is needed to determine whether this is an adaptive response to nutrient deprivation in disease-related cachexia or whether the increased FGF21 values contribute to the catabolic state.

Moraxella catarrhalis decreases antiviral innate immune responses by down-regulation of TLR3 via inhibition of p53 in human bronchial epithelial cells.

Chronic obstructive pulmonary disease (COPD) is complicated by infectious exacerbations with acute worsening of respiratory symptoms. Coinfections of bacterial and viral pathogens are associated with more severe exacerbations. Moraxella catarrhalis is one of the most frequent lower respiratory tract pathogens detected in COPD. We therefore studied the impact of M. catarrhalis on the antiviral innate immune response that is mediated via TLR3 and p53. Molecular interactions between M. catarrhalis and normal human bronchial epithelial (NHBE) cells as well as Beas-2B cells were studied using flow cytometry, quantitative PCR analysis, chromatin immunoprecipitation, RNA interference, and ELISA. M. catarrhalis induces a significant down-regulation of TLR3 in human bronchial epithelial cells. In M. catarrhalis-infected cells, expression of p53 was decreased. We detected a reduced binding of p53 to the tlr3 promoter, resulting in reduced TLR3 gene transcription. M. catarrhalis diminished the TLR3-dependent secretion of IFN-ß, IFN-λ, and chemokine (C-X-C motif) ligand 8. In addition in M. catarrhalis infected cells, expression of rhinovirus type 1A RNA was increased compared with uninfected cells. M. catarrhalis reduces antiviral defense functions of bronchial epithelial cells, which may increase susceptibility to viral infections.-Heinrich, A., Haarmann, H., Zahradnik, S., Frenzel, K., Schreiber, F., Klassert, T. E., Heyl, K. A., Endres, A.-S., Schmidtke, M., Hofmann, J., Slevogt, H. Moraxella catarrhalis decreases antiviral innate immune responses by down-regulation of TLR3 via inhibition of p53 in human bronchial epithelial cells.

Human papillomavirus E6/E7 mRNA testing has higher specificity than liquid-based DNA testing in the evaluation of cervical intraepithelial neoplasia.

OBJECTIVE: To examine the specificity of human papillomavirus (HPV) E6/E7 mRNA testing for intraepithelial precursor lesions and invasive carcinoma of the uterine cervix in 358 women and compare the results with those of the most widely used DNA technique. STUDY DESIGN: For HPV E6/E7 mRNA testing an amplification assay was used. For DNA determination a hybridization assay was applied. Both techniques were used simultaneously in patients with normal morphology (150), cervical intraepithelial neoplasia (173) and invasive carcinoma of the cervix (35). RESULTS: HPV DNA positivity rates were significantly higher than E6/E7 mRNA in women with normal morphology (21-7%), cervical intraepithelial neoplasia (CIN) 1 and 2 (75-43%), and CIN 3 (93-63%). In invasive cervical carcinoma, both methods tested equally high (94% vs. 97%). Considering that E6/E7 up-regulation represents the initial step in cervical carcinogenesis, it can be assumed that this test allows a more specific detection of lesions with a potential for progression. CONCLUSION: HPV E6/E7 mRNA may serve as a more specific discriminator between transient cervical dysplasias and potentially progressive lesions. Accordingly, testing for high-risk HPV E6/E7 mRNA might reduce the psychologic burden associated with HPV-DNA testing.

Functional analysis of complex hepatitis B virus variants associated with development of liver cirrhosis.

BACKGROUND & AIMS: Development of cirrhosis in renal transplant recipients with chronic hepatitis B is associated with the accumulation of complex hepatitis B virus (HBV) variants carrying deletions in the C gene and/or preS region and deletions/insertions in the core promoter. Here, we characterized for the first time the phenotype of these complex HBV variants. METHODS: Representative full-length genomes of the HBV variants that were isolated and cloned from serum and liver of an immunosuppressed renal transplant recipient before and during end-stage liver disease were transfected into the human hepatoma cell line HuH7 and functionally analyzed. RESULTS: The variant genomes showed considerably reduced levels of precore and surface messenger RNA (mRNA) and of the major spliced pregenomic RNA, an increased level of pregenomic RNA, and a partial or complete defect in hepatitis B e antigen, core, and surface protein expression/secretion. Very low amounts of variant core protein with internal deletion were detectable. Reduced hepatitis B surface antigen secretion of some variants correlated with aberrant localization of surface proteins in endoplasmic reticulum. Despite the defects in viral protein expression, enhanced replication and enrichment in competition to wild-type HBV were observed. Enhanced reverse transcription and possibly increased levels of pregenomic RNA seem to be responsible for this effect. CONCLUSIONS: Development of cirrhosis is associated with accumulation of complex variants, which exhibit a drastically altered phenotype combining enhanced replication with defects in protein expression. This phenotype appears to be based on the major mutations in the core promoter and C gene but is considerably influenced by additional mutations throughout the genome.

Recurrent high level parvovirus B19/genotype 2 viremia in a renal transplant recipient analyzed by real-time PCR for simultaneous detection of genotypes 1 to 3.

Organ transplant recipients infected with parvovirus B19 frequently develop persistent viremia associated with chronic anemia and pure red cell aplasia. In this study, a male renal transplant recipient who had been infected with parvovirus B19/genotype 2 after renal transplantation at the age of 34 years is described. The patient was repeatedly treated with high dose intravenous immunoglobulin (IVIG) that resulted in the resolvement of symptoms but not in virus eradication. During an observation period of 33 months after transplantation three phases associated with high parvovirus B19 viremia were observed. Both the first and the second viremic phases were combined with severe anemia. Parvovirus B19 specific IgM-antibodies were initially detected at the beginning of the second phase in continually rising concentrations. Initially eradication of the virus by immunoglobulin therapy was reported after the first viremic phase [Liefeldt et al. (2002): Nephrol Dial Transplant 17:1840-1842]. Retrospectively this statement has to be corrected. It was based on the use of a qualitative PCR assay specific for parvovirus B19 genotype 1 associated with reduced sensitivity for detection of genotype 2. After sequence analysis of the viral DNA and adjustment of a real-time PCR assay (TaqMan) for quantitative detection of all three B19 virus genotypes analysis of consecutive serum samples allowed the demonstration of long lasting phases with reduced viral loads following IVIG-treatment. These results demonstrate that IVIG treatment of parvovirus B19-triggered anemia in transplant recipients offers an opportunity to resolve symptoms, but does not guarantee eradication of the virus. Since reactivation of parvovirus B19 infection can result in high virus load associated with the recurrence of symptoms repeated screening for viral DNA is recommended using the TaqMan system established for quantitative detection of all three genotypes of parvovirus B19.