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Routine vaccination of elderly people against pneumococcal diseases is recommended in many countries. National guidelines differ, recommending either the 23-valent polysaccharide vaccine (PPV23), the 13-valent conjugate vaccine (PCV13) or both. Considering the ongoing debate on the effectiveness of PPV23, we performed a systematic literature review and meta-analysis of the vaccine efficacy/effectiveness (VE) of PPV23 against invasive pneumococcal disease (IPD) and pneumococcal pneumonia in adults aged ≥60 years living in industrialized countries. We searched for pertinent clinical trials and observational studies in databases MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. We assessed the risk of bias of individual studies using the Cochrane Risk of Bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies. We rated the overall quality of the evidence by GRADE criteria. We performed meta-analyses of studies grouped by outcome and study design using random-effects models. We applied a sensitivity analysis excluding studies with high risk of bias. We identified 17 eligible studies. Pooled VE against IPD (by any serotype) was 73% (95%CI: 10-92%) in four clinical trials, 45% (95%CI: 15-65%) in three cohort studies, and 59% (95%CI: 35-74%) in three case-control studies. After excluding studies with high risk of bias, pooled VE against pneumococcal pneumonia (by any serotype) was 64% (95%CI: 35-80%) in two clinical trials and 48% (95%CI: 25-63%) in two cohort studies. Higher VE estimates in trials (follow-up ~2.5 years) than in observational studies (follow-up ~5 years) may indicate waning protection. Unlike previous meta-analyses, we excluded two trials with high risk of bias regarding the outcome pneumococcal pneumonia, because diagnosis was based on serologic methods with insufficient specificity. Our meta-analysis revealed significant VE of PPV23 against both IPD and pneumococcal pneumonia by any serotype in the elderly, comparable to the efficacy of PCV13 against vaccine-serotype disease in a recent clinical trial in elderly people. Due to its broader serotype coverage and the decrease of PCV13 serotypes among adults resulting from routine infant immunization with PCV13, PPV23 continues to play an important role for protecting adults against IPD and pneumococcal pneumonia.

The kinetoplastid protozoan parasites belonging to the genus are the causative agents of different clinical forms of leishmaniasis, a vector-borne infectious disease with worldwide prevalence. The protective host immune response against parasites relies on myeloid cells such as dendritic cells and macrophages in which upon stimulation by cytokines (e.g., interferon-γ) a complex network of signaling pathways is switched on leading to strong antimicrobial activities directed against the intracellular parasite stage. The regulation of these pathways classically depends on post-translational modifications of proteins, with phosphorylation events playing a cardinal role. parasites deactivate their phagocytic host cells by inducing specific mammalian phosphatases that are capable to impede signaling. On the other hand, there is now also evidence that spp. themselves express phosphatases that might target host cell molecules and thereby facilitate the intracellular survival of the parasite. This review will present an overview on the modulation of host phosphatases by parasites as well as on the known families of phosphatases and their possible function as virulence factors. A more detailed understanding of the role of phosphatases in -host cell interactions might open new avenues for the treatment of non-healing, progressive forms of leishmaniasis.

Background Infants < 3 months of age are at highest risk for developing severe complications after pertussis. The majority of pregnant women has low concentrations of pertussis-specific antibodies and thus newborns are insufficiently protected by maternally transferred antibodies. Acellular pertussis vaccination during pregnancy was recently implemented in various countries. Here, we assessed the evidence for safety and effectiveness of pertussis vaccination during pregnancy. Methods We searched Medline, Embase, and ClinicalTrials.gov from January 1st 2010 to January 10th 2019. We assessed risk of bias (ROB) using the Cochrane ROB tool and ROBINS-I. We evaluated the quality of evidence using the GRADE approach. Results We identified 1273 articles and included 22 studies (14 for safety; 8 for effectiveness), comprising 1.4 million pregnant women in safety studies and 855,546 mother-infant-pairs in effectiveness studies. No significant differences between vaccinated and unvaccinated women and their infants were observed for safety outcomes with the exception of fever and chorioamnionitis. Compared to no vaccination, three studies showed a significantly increased relative risk for the presence of the ICD-9 code for chorioamnionitis in electronic patient data after pertussis vaccination. However, no study reported an increased risk for clinical sequelae of chorioamnionitis after vaccination during pregnancy, such as preterm birth or neonatal intensive care unit admission. Vaccine effectiveness against pertussis in infants of immunized mothers ranged from 69 to 91% for pertussis prevention, from 91 to 94% for prevention of hospitalization and was 95% for prevention of death due to pertussis. Risk of bias was serious to critical for safety outcomes and moderate to serious for effectiveness outcomes. GRADE evidence quality was moderate to very low, depending on outcome. Conclusion Although an increased risk for a diagnosis of fever and chorioamnionitis was detected in pregnant women after pertussis vaccination, there was no association with a higher frequency of clinically relevant sequelae. Vaccine effectiveness for prevention of infant pertussis, hospitalization and death is high. Pertussis vaccination during pregnancy has an overall positive benefit-risk ratio. In view of the overall quality of available evidence ongoing surveillance of chorioamnionitis and its potential sequelae is recommended when pertussis vaccination in pregnancy is implemented. Trial registration PROSPERO CRD42018087814 , CRD42018090357 .

Arginase 1 (Arg1), which converts l-arginine into ornithine and urea, exerts pleiotropic immunoregulatory effects. However, the function of Arg1 in inflammatory bowel disease (IBD) remains poorly characterized. Here, we found that Arg1 expression correlated with the degree of inflammation in intestinal tissues from IBD patients. In mice, Arg1 was upregulated in an IL-4/IL-13- and intestinal microbiota-dependent manner. Tie2-Cre Arg1fl/fl mice lacking Arg1 in hematopoietic and endothelial cells recovered faster from colitis than Arg1-expressing (Arg1fl/fl) littermates. This correlated with decreased vessel density, compositional changes in intestinal microbiota, diminished infiltration by myeloid cells, and an accumulation of intraluminal polyamines that promote epithelial healing. The proresolving effect of Arg1 deletion was reduced by an l-arginine-free diet, but rescued by simultaneous deletion of other l-arginine-metabolizing enzymes, such as Arg2 or Nos2, demonstrating that protection from colitis requires l-arginine. Fecal microbiota transfers from Tie2-Cre Arg1fl/fl mice into WT recipients ameliorated intestinal inflammation, while transfers from WT littermates into Arg1-deficient mice prevented an advanced recovery from colitis. Thus, an increased availability of l-arginine as well as altered intestinal microbiota and metabolic products accounts for the accelerated resolution from colitis in the absence of Arg1. Consequently, l-arginine metabolism may serve as a target for clinical intervention in IBD patients.

To allow an efficient protection against viruses like the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2), it is important to avoid their spreading by using filtering face pieces (FFP), which are categorized by different standards according to their filtration efficiency. In this study, we subjected six brands of FFP2 standard masks to three different conditions and subsequently analysed them for their filtration performance to evaluate potentials for reusability. The conditions comprised changes of temperature and air humidity, an exposure to isopropyl alcohol (IPA) and an autoclave sterilization. While four of six masks consisted of electrostatically treated melt blown non-wovens, two masks were fabricated using a nanofibrous multilayer system. Due to the absence of prior electrostatic treatment, the nano-masks did not show a significant change in filtration efficiency when discharged by IPA, unlike the melt blown nonwoven masks showing a significant decrease of filtration efficiency down to around 50% at a particle size of 0.3 μm. However, most melt blown masks maintained a sufficient filtration efficiency after all other treatments with even better results than the nanofibrous masks. This was particularly the case for the capacity to filter smallest particles/droplets with a size of around 0.1 μm, which is below the range of typical filtering standards and important for the retention of virally contaminated nano-aerosols or unattached viruses. After temperature/humidity variation and autoclave sterilization, melt blown masks were able to retain a filtration efficiency up to over 90% at 0.1 μm contrary to nano-masks showing a decrease down to around 70%. Based on their better filtration performance, lower price and potential reusability, we conclude that electret melt blown masks are the preferable type of FFP2 masks.

Background In many industrialized countries routine vaccination with the 23-valent pneumococcal polysaccharide vaccine (PPSV-23) is recommended to prevent pneumococcal disease in the elderly. However, vaccine-induced immunity wanes after a few years, and there are controversies around revaccination with PPSV-23. Here, we systematically assessed the effectiveness and safety of PPSV-23 revaccination. Method We conducted a systematic literature review in MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from inception to June 2015. We included all study types that compared effectiveness, immunogenicity and/or safety of PPSV-23 as a primary vs. a revaccination dose in persons aged 50 years and older. With respect to immunogenicity, we calculated the ratio of geometric mean antibody concentrations and opsonophagocytic indexes at identical time-points after primary and revaccination. Additionally, we compared rates and severity of adverse events (AEs) after primary and revaccination. Results We included 14 observational studies. 10 studies had a prospective design and analysed data on (i) the same individuals after a first and a second dose of PPSV-23 given 1 to 10 years later ( n = 5) or (ii) two groups consisting of participants receiving PPSV-23 who were either vaccine-naïve or had received a first PPSV-23 dose 3 to 13 years earlier ( n = 5). Three studies used electronic data bases to compare AEs after primary vs. revaccination doses of PPSV-23 after 1 to 10 years and one study had a cross-sectional design. Number of participants in the non-register-based and register-based studies ranged from 29 to 1414 and 360 to 316,000, respectively. 11 out of 14 included studies were at high risk of bias, three studies had an unclear risk of bias. None of the studies reported data on clinical effectiveness. Immunogenicity studies revealed that during the first two months antibody levels tended to be lower after revaccination as compared to primary vaccination. Thereafter, no obvious differences in antibody levels were observed. Compared to primary vaccination, revaccination was associated with an increased risk of local and systemic AEs, which, however, were usually mild and self-limiting. The risk and severity of AEs appeared to decrease with longer intervals between primary and revaccination. Conclusion Data comparing the effectiveness of primary vs. revaccination with PPSV-23 are still lacking, because there are no studies with clinical endpoints. Data from observational studies indicates that revaccination with PPSV-23 is likely to induce long-term antibody levels that are comparable to those after primary vaccination. Given the high disease burden and the waning of vaccine-induced immunity, revaccination with PPSV-23 could be considered in the elderly. The increased risk of local and systemic AEs can likely be mitigated when giving revaccination at least five years after the primary dose. Adequately powered randomized controlled trials using clinical endpoints are urgently needed.

Background Malaria occurred endemically in Germany until the twentieth century. Climate change and globalization are known to promote the spreading of malaria. Erlangen is a city with just under 120,000 inhabitants located in the Nürnberg metropolitan region, Federal State of Bavaria, Southern Germany. Historical findings, current climate data, microbiological data (local and state level) and vector surveillance data are used to estimate the risk of re-emergence and autochthonous transmission of malaria in the area of Erlangen. Methods Historical data was obtained by searching literature. Climatic data were retrieved from the German Climate Data Centre. Data on reported (supra-)regional infections were obtained from the Robert-Koch Institute. Cases of malaria diagnosed at the Institute of Clinical Microbiology, Immunology and Hygiene (University Hospital Erlangen) complement this data. The citizen science project “Mückenatlas” (Mosquito Atlas), the German mosquito database (CULBASE) and the company Biogents AG provided mosquito surveillance data. Results Malaria was highly endemic in Erlangen in the nineteenth century, with 18% of hospitalized patients suffering from this disease in 1860, but disappeared during the first half of the twentieth century. After the end of World War II, autochthonous ‘malaria tertiana’ (tertian malaria) occurred in neighbouring Nürnberg, demonstrating the regional malaria potential. In recent decades, the average monthly temperature increased by 1.6 °C. In Erlangen and the surrounding area, three potential vectors of tertian malaria parasites are prevalent ( Anopheles messeae, Anopheles maculipennis sensu stricto, and Anopheles plumbeus ). In addition, Anopheles daciae, which has unknown potential of Plasmodium transmission, and Anopheles claviger sensu lato have been detected. In recent years, malaria diagnosed in Erlangen mainly resulted from travelling to Africa. Plasmodium vivax accounted for only a small proportion of these cases (2010–2023: n = 5, 17%). Conclusion Future autochthonous transmission of malaria parasites in Erlangen is possible, although re-establishment of a natural transmission cycle is currently unlikely. In order to avoid unexpected autochthonous malaria, surveillance and prevention measures should be considered. Patients with fever after visiting endemic areas need to be analysed for Plasmodium infection.

Classically activated macrophages are targets of intracellular bacteria such as Mycobacteria tuberculosis . Murray and colleagues find that such pathogens induce arginase 1 in these macrophages to block the production of antibacterial nitric oxide. Toll-like receptor (TLR) signaling in macrophages is required for antipathogen responses, including the biosynthesis of nitric oxide from arginine, and is essential for immunity to Mycobacterium tuberculosis , Toxoplasma gondii and other intracellular pathogens. Here we report a 'loophole' in the TLR pathway that is advantageous to these pathogens. Intracellular pathogens induced expression of the arginine hydrolytic enzyme arginase 1 (Arg1) in mouse macrophages through the TLR pathway. In contrast to diseases dominated by T helper type 2 responses in which Arg1 expression is greatly increased by interleukin 4 and 13 signaling through the transcription factor STAT6, TLR-mediated Arg1 induction was independent of the STAT6 pathway. Specific elimination of Arg1 in macrophages favored host survival during T. gondii infection and decreased lung bacterial load during tuberculosis infection.

Infection of specific pathogen-free mice with lymphocytic choriomeningitis virus (LCMV) is a widely used model to study antiviral T-cell immunity. Infections in the real world, however, are often accompanied by coinfections with unrelated pathogens. Here we show that in mice, systemic coinfection with E. coli suppresses the LCMV-specific cytotoxic T-lymphocyte (CTL) response and virus elimination in a NK cell- and TLR2/4-dependent manner. Soluble TLR4 ligand LPS also induces NK cell-mediated negative CTL regulation during LCMV infection. NK cells in LPS-treated mice suppress clonal expansion of LCMV-specific CTLs by a NKG2D- or NCR1-independent but perforin-dependent mechanism. These results suggest a TLR4-mediated immunoregulatory role of NK cells during viral-bacterial coinfections. Exposure to multiple pathogens is common in nature, yet interactions between the immune components targeting bacterial and viral pathogens during co-infection are poorly understood. Here the authors show that bacteria-derived LPS induces cytotoxic NK cells that suppress antiviral CD8 T cell response.

Infection with the intracellular bacterium Coxiella (C.) burnetii can cause chronic Q fever with severe complications and limited treatment options. Here, we identify the enzyme cis‐aconitate decarboxylase 1 (ACOD1 or IRG1) and its product itaconate as protective host immune pathway in Q fever. Infection of mice with C. burnetii induced expression of several anti‐microbial candidate genes, including Acod1 . In macrophages, Acod1 was essential for restricting C. burnetii replication, while other antimicrobial pathways were dispensable. Intratracheal or intraperitoneal infection of Acod1 −/− mice caused increased C. burnetii burden, weight loss and stronger inflammatory gene expression. Exogenously added itaconate restored pathogen control in Acod1 −/− mouse macrophages and blocked replication in human macrophages. In axenic cultures, itaconate directly inhibited growth of C. burnetii . Finally, treatment of infected Acod1 −/− mice with itaconate efficiently reduced the tissue pathogen load. Thus, ACOD1‐derived itaconate is a key factor in the macrophage‐mediated defense against C. burnetii and may be exploited for novel therapeutic approaches in chronic Q fever. Synopsis The intracellular bacterium Coxiella burnetii causes the anthropozoonotic infection Q fever. Most patients control and resolve infection, but some develop chronic disease. Finding out how macrophages inhibit bacterial replication may explain susceptibility and suggest new therapies. Coxiella burnetii induces expression of the enzyme Aconitate Decarboxylase 1 (ACOD1) in mouse and human macrophages. Acod1 −/− mice and macrophages do not generate the immunometabolite itaconate and fail to control C. burnetii replication in vitro and in vivo . Itaconate directly blocks C. burnetii replication at physiological concentrations. Treatment with itaconate restores control of C. burnetii in macrophages and in mice. Human macrophages generate less itaconate and allow C. burnetii replication, which is inhibited by exogenous itaconate. Graphical Abstract The intracellular bacterium Coxiella burnetii causes the anthropozoonotic infection Q fever. Most patients control and resolve infection, but some develop chronic disease. Finding out how macrophages inhibit bacterial replication may explain susceptibility and suggest new therapies.