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Zusammenfassung. Die Lyme-Borreliose wird durch Borrelia burgdorferi sensu lato hervorgerufen und ist eine Zecken-übertragene Infektion, die vor allem in der nördlichen Hemisphäre vorkommt. Die Infektion beginnt typischerweise mit einer lokalisierten Infektion, die sich als expandierende Hautläsion mit zentraler Aufhellung manifestiert, dem sogenannten Erythema migrans. Unbehandelt kann es zu einer frühen disseminierten Form führen, welche häufig zu einem Befall des ZNS und weniger häufig zu Karditis führt. Späte Infektionsmanifestationen sind typischerweise die Arthritis und ein charakteristischer Hautbefall, die Acrodermatitis atrophicans. Die chronologische Abfolge der Stadien ist jedoch nicht zwingend und auch isolierte «späte» Manifestationen können der Erstpräsentation der Infektion entsprechen. Mit der Ausnahme des Erythema migrans, welches eine Blickdiagnose und keine Serologie erfordert, basiert die Diagnose aller anderen Infektionsmanifestationen auf einer Kombination der typischen klinischen Präsentation und dem serologischen Nachweis einer Borrelien-Infektion. Alle Stadien der Borrelien Infektion sprechen gut auf Antibiotika an, allen voran beta-Lactam-Derivate und Tetracycline. In einer Minderheit der Patienten kann es zu persistierenden, postinfektiösen Syndromen kommen.

Clinical presentation and Treatment of Lyme Disease

As innate sentinels in the lung, alveolar macrophages (AMs) play a critical role during Mycobacterium tuberculosis (Mtb) infection as the first cells to encounter bacteria. We previously showed that AMs initially respond to Mtb infection in vivo by mounting a cell-protective, rather than pro-inflammatory response, yet whether the AM response could be modified by environmental factors was unknown. Here, we characterize how previous exposure to mycobacteria, either through subcutaneous vaccination with Mycobacterium bovis (scBCG) or through a contained Mtb infection (coMtb), impacts the initial response by AMs and early innate response in the lung. We find that both scBCG and coMtb accelerate early innate cell activation and recruitment and generate a stronger pro-inflammatory AM response to Mtb in vivo. AMs from scBCG vaccinated mice mount a robust interferon response, while AMs from coMtb mice produce a broader and more diverse inflammatory response. Using single-cell RNA-sequencing, we identify exposure-induced changes to airway-resident cells, with scBCG and coMtb enriching for different AM subpopulations. Ex vivo stimulation assays reveal that AMs from scBCG and coMtb mice switch on an interferon-dependent response, which is absent in AMs from unexposed mice. Overall, our studies reveal significant, durable, and cell-intrinsic modifications to AMs following exposure to mycobacterium, and comparison of scBCG and coMtb models reveals that AMs can be reprogrammed into more than one state. These findings highlight the plasticity of innate responses in the airway and underscore the unexplored potential of targeting AMs through vaccination or host-directed therapy to augment host responses.

Previous studies have identified whole-blood transcriptional risk and disease signatures for tuberculosis; however, several lines of evidence suggest that these signatures primarily reflect bacterial burden, which increases before symptomatic disease. We found that the peripheral blood transcriptome of mice with contained Mycobacterium tuberculosis infection (CMTI) has striking similarities to that of humans with active tuberculosis and that a signature derived from these mice predicts human disease with accuracy comparable to that of signatures derived directly from humans. A set of genes associated with immune defense are up-regulated in mice with CMTI but not in humans with active tuberculosis, suggesting that their up-regulation is associated with bacterial containment. A signature comprising these genes predicts both protection from tuberculosis disease and successful treatment at early time points where current signatures are not predictive. These results suggest that detailed study of the CMTI model may enable identification of biomarkers for human tuberculosis.

BACKGROUND: Before April 2022, monkeypox virus infection in humans was seldom reported outside African regions where it is endemic. Currently, cases are occurring worldwide. Transmission, risk factors, clinical presentation, and outcomes of infection are poorly defined. METHODS: We formed an international collaborative group of clinicians who contributed to an international case series to describe the presentation, clinical course, and outcomes of polymerase-chain-reaction-confirmed monkeypox virus infections. RESULTS: We report 528 infections diagnosed between April 27 and June 24, 2022, at 43 sites in 16 countries. Overall, 98% of the persons with infection were gay or bisexual men, 75% were White, and 41% had human immunodeficiency virus infection; the median age was 38 years. Transmission was suspected to have occurred through sexual activity in 95% of the persons with infection. In this case series, 95% of the persons presented with a rash (with 64% having ≤10 lesions), 73% had anogenital lesions, and 41% had mucosal lesions (with 54 having a single genital lesion). Common systemic features preceding the rash included fever (62%), lethargy (41%), myalgia (31%), and headache (27%); lymphadenopathy was also common (reported in 56%). Concomitant sexually transmitted infections were reported in 109 of 377 persons (29%) who were tested. Among the 23 persons with a clear exposure history, the median incubation period was 7 days (range, 3 to 20). Monkeypox virus DNA was detected in 29 of the 32 persons in whom seminal fluid was analyzed. Antiviral treatment was given to 5% of the persons overall, and 70 (13%) were hospitalized; the reasons for hospitalization were pain management, mostly for severe anorectal pain (21 persons); soft-tissue superinfection (18); pharyngitis limiting oral intake (5); eye lesions (2); acute kidney injury (2); myocarditis (2); and infection-control purposes (13). No deaths were reported. CONCLUSIONS: In this case series, monkeypox manifested with a variety of dermatologic and systemic clinical findings. The simultaneous identification of cases outside areas where monkeypox has traditionally been endemic highlights the need for rapid identification and diagnosis of cases to contain further community spread.

While an increased risk of active and latent tuberculosis infection (LTBI) in people with type-2 diabetes (DM) has been demonstrated, it is less well characterized whether LTBI is associated with an increased risk of developing DM. We investigated the link between LTBI and DM in people living with HIV in the Swiss HIV Cohort Study via time-dependent Cox proportional hazards models. We found that LTBI significantly increased the risk of developing DM (HR = 1.47), which was robust across different adjustment and censoring techniques. Our results thus suggest that LTBI may be associated with an increased risk of developing DM.

This case study discusses the management of a disseminated Mycobacterium simiae and Mycobacterium avium infection causing an immune reconstitution inflammatory syndrome in a 52-year-old woman with HIV infection. Disseminated M. avium infections have extensively been described in HIV patients; however, reports of infections with M. simiae are rare. Treatment of M. simiae infections is challenging due to its high rates of natural drug resistances, and thus far, no standard treatment regimen exists.

Objectives: Immune activation, among others driven by interferon (IFN)-α and IFN-γ activation, is a main feature of progressive HIV infection. Suppressor of cytokine signaling (SOCS) 1 and 3 are negative feedback regulators of the IFN-α and IFN-γ axis. Here, we analyzed the role of 9 single-nucleotide polymorphisms (SNPs) within SOCS-1 and SOCS-3 genes for their association with an HIV progression rate in a cohort of 318 rapid vs 376 slow progressors from the Swiss HIV Cohort Study. Design and methods: We analyzed 9 SNPs, which we have identified in Swiss blood donors, in a cohort of HIV-infected patients (n = 1144), which have been categorized according to the decline in CD4 T-cell counts. In all the conducted analyses, we focused on the comparison between rapid and slow progressors with regard to SNPs in SOCS-1 and SOCS-3 and with regard to haplotypes using multivariate logistic regression models. Results: Three SOCS-1 SNPs (rs193779, rs33989964, and rs4780355) are associated with a risk reduction for rapid progression. Two of these SNPs, rs33989964 and rs4780355, are in strong linkage disequilibrium, forming a frequent haplotype. Homozygous carriers of this haplotype are also associated with a risk reduction for rapid progression. By contrast, the minor TT genotype of rs33977706 is associated with twice the risk for rapid progression. No associations have been observed for the 4 SOCS-3 SNPs or the major SOCS-3 haplotypes. Conclusions: Our data suggest that SNPs in SOCS-1 are associated with HIV disease progression and speak in favor that immune activation is causal for the progressive immunodeficiency.

Mycobacterium tuberculosis (MTB) is notorious for persisting within host macrophages. Efflux pumps decrease intracellular drug levels, thus fostering persistence of MTB during therapy. Isoniazid (INH) and pyrazinamide (PZA) are substrates of the efflux pump breast cancer resistance protein-1 (BCRP-1), which is inhibited by chloroquine (CQ). In this study, BCRP-1 was found to be expressed on macrophages of human origin and on foamy giant cells at the site of MTB infection. In the current in vitro study, interferon-gamma (IFNγ) increased the expression of BCRP-1 in macrophages derived from the human monocytic leukaemia cell line THP-1. Using a BCRP-1-specific fluorescent dye and radioactively labelled INH, it was demonstrated that efflux from macrophages increased upon activation with IFNγ. CQ was able to inhibit active efflux and augmented the intracellular concentrations both of INH and the dye. In agreement, CQ and specific inhibition of BCRP-1 increased the antimycobacterial activity of INH against intracellular MTB. Although PZA behaved differently, CQ had comparable advantageous effects on the intracellular pharmacokinetics and activity of PZA. The adjunctive effects of CQ on intracellular killing of MTB were measurable at concentrations achievable in humans at approved therapeutic doses. Therefore, CQ, a widely used and worldwide available drug, may potentiate the efficacy of standard MTB therapy against bacteria in the intracellular compartment.

Infections caused by carbapenemase-producing, multidrug-resistant (MDR), or extensively drug-resistant (XDR) Gram-negative bacteria constitute a major therapeutic challenge. Whether combination antibiotic therapy is superior to monotherapy remains unknown. In this systematic review and meta-analysis OVID MEDLINE, EMBASE, PubMed, The Cochrane Library, and Scopus databases were searched for randomized controlled trials (RCTs) and observational studies published by December 2016 comparing mono- with combination antibiotic therapy for infections with carbapenemase-producing, MDR, or XDR Gram-negative bacteria. Mortality and clinical cure rates served as primary and secondary outcome measures, respectively. Of 8847 initially identified studies, 53 studies – covering pneumonia (n = 10 studies), blood stream (n = 15), osteoarticular (n = 1), and mixed infections (n = 27) - were included. 41% (n = 1848) of patients underwent monotherapy, and 59% (n = 2666) combination therapy. In case series/cohort studies (n = 45) mortality was lower with combination- vs. monotherapy (RR 0.83, CI 0.73–0.93, p = 0.002, I2 = 24%). Subgroup analysis revealed lower mortality with combination therapy with at least two in-vitro active antibiotics, in blood stream infections, and carbapenemase-producing Enterobacteriaceae. No mortality difference was seen in case-control studies (n = 6) and RCTs (n = 2). Cure rates did not differ regardless of study type. The two included RCTs had a high and unknown risk of bias, respectively. 16.7% (1/6) of case-control studies and 37.8% (17/45) of cases series/cohort studies were of good quality, whereas quality was poor in the remaining studies. In conclusion, combination antimicrobial therapy of multidrug-resistant Gram-negative bacteria appears to be superior to monotherapy with regard to mortality.

Alveolar macrophages (AMs) are the first cells to be infected during Mycobacterium tuberculosis (M.tb.) infection. Thus, the AM response to infection is the first of many steps leading to initiation of the adaptive immune response required for efficient control of infection. A hallmark of M.tb. infection is the slow initiation of the adaptive response, yet the mechanisms responsible for this are largely unknown. To study the initial AM response to infection, we developed a system to identify, sort, and analyze M.tb.-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described using in vitro systems, M.tb.-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment but not bacterial virulence. Computational approaches including pathway analysis and transcription factor motif enrichment analysis identify NRF2 as a master regulator of the response. Using knockout mouse models, we demonstrate that NRF2 drives expression of the cell-protective signature in AMs and impairs the control of early bacterial growth. AMs up-regulate a substantial pro-inflammatory response to M.tb. infection only 10 days after infection, yet comparisons with bystander AMs from the same infected animals demonstrate that M.tb.-infected AMs generate a less robust inflammatory response than the uninfected cells around them. Our findings demonstrate that the initial macrophage response to M.tb. in the lung is far less inflammatory than has previously been described by in vitro systems and may impede the overall host response to infection.

An efficacious vaccine against adult tuberculosis (TB) remains elusive. Progress is hampered by an incomplete understanding of the immune mechanisms that protect against infection with Mycobacterium tuberculosis (Mtb), the causative agent of TB1. Over 90% of people who become infected with Mtb mount an immune response that contains the bacteria indefinitely, leading to a state known as “latent TB infection” (LTBI)2. A significant body of epidemiologic evidence indicates that LTBI protects against active TB after re-exposure, offering an intriguing avenue to identifying protective mechanisms3, 4. We show that in a mouse model, LTBI is highly protective against infection with Mtb for up to 100 days following aerosol challenge. LTBI mice are also protected against heterologous bacterial challenge (Listeria monocytogenes) and disseminated melanoma suggesting that protection is in part mediated by alterations in the activation state of the innate immune system. Protection is associated with elevated activation of alveolar macrophages (AM), the first cells that respond to inhaled Mtb, and accelerated recruitment of Mtb-specific T cells to the lung parenchyma upon aerosol challenge. Systems approaches, including transcriptome analysis of both naïve and infected AMs, as well as ex vivo functional assays, demonstrate that LTBI reconfigures the response of tissue resident AMs.. Furthermore, we demonstrate that both LTBI mice and latently infected humans show similar alterations in the relative proportions of circulating innate immune cells, suggesting that the same cellular changes observed in the LTBI mouse model are also occurring in humans. Therefore, we argue that under certain circumstances, LTBI could be beneficial to the host by providing protection against subsequent Mtb exposure.

Alveolar macrophages (AMs) are the first cells to be infected duringMycobacterium tuberculosis(Mtb) infection. Thus the AM response to infection is the first of many steps leading to initiation of the adaptive immune response, which is required for efficient control of infection. A hallmark of Mtb infection is the delay of the adaptive response, yet the mechanisms responsible for this delay are largely unknown. We developed a system to identify, sort and analyze Mtb-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described usingin vitrosystems, we find that Mtb-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment and not dependent on bacterial virulence. Computational approaches including pathway analysis and transcription factor binding motif enrichment analysis identify Nrf2 as a master regulator of the response of AMs to Mtb infection. Using knock-out mouse models, we demonstrate that Nrf2 drives the expression of the cell protective transcriptional program and impairs the ability of the host to control bacterial growth over the first 10 days of infection. Mtb-infected AMs exhibit a highly delayed pro-inflammatory response, and comparisons with uninfected AMs from the same infected animals demonstrate that inflammatory signals in the lung environment are blocked in the Mtb-infected cells. Thus, we have identified a novel lung-specific transcriptional response to Mtb infection that impedes AMs from responding rapidly to intracellular infection and thereby hinders the overall immune response.One Sentence SummaryIn response to Mtb infectionin vivo, alveolar macrophages fail to up-regulate the canonical pro-inflammatory innate response and instead induce an Nrf2-dependent cell protective transcriptional program, which in turn impairs the host’s control of bacterial growth.

Alveolar macrophages (AMs) are the first cells to be infected during Mycobacterium tuberculosis (M.tb.) infection. Thus the AM response to infection is the first of many steps leading to initiation of the adaptive immune response, required for efficient control of infection. A hallmark of M.tb. infection is the slow initiation of the adaptive response, yet the mechanisms responsible for this are largely unknown. To study the initial AM response to infection, we developed a system to identify, sort and analyze M.tb.-infected AMs from the lung within the first 10 days of infection. In contrast to what has been previously described using in vitro systems, M.tb.-infected AMs up-regulate a cell-protective antioxidant transcriptional signature that is dependent on the lung environment but not bacterial virulence. Computational approaches including pathway analysis and transcription factor motif enrichment analysis identify NRF2 as a master regulator of the response. Using knock-out mouse models, we demonstrate that NRF2 drives expression of the cell protective signature in AMs and impairs the control of early bacterial growth. AMs up-regulate a significant pro-inflammatory response to M.tb. infection only 10 days following infection, yet comparisons with bystander AMs from the same infected animals demonstrate that M.tb.-infected AMs generate a less robust inflammatory response than the uninfected cells around them. Our findings demonstrate that the initial macrophage response to M.tb. in the lung is far less inflammatory than has previously been described by in vitro systems and may impede the overall host response to infection.

Host-directed therapies against HIV-1 are thought to be critical for long term containment of the HIV-1 pandemic but remain elusive. Because HIV-1 infects and manipulates important effectors of both the innate and adaptive immune system, identifying modulations of the host cell systems in humans during HIV-1 infection may be crucial for the development of immune based therapies. Here, we quantified the changes of the proteome in human CD4+ T cells upon HIV-1 infection, both in vitro and in vivo. A SWATH-MS approach was used to measure the proteome of human primary CD4+ T cells infected with HIV-1 in vitro as well as CD4+ T cells from HIV-1-infected patients with paired samples on and off antiretroviral treatment. In the in vitro experiment, the proteome of CD4+ T cells was quantified over a time course following HIV-1 infection. 1,725 host cell proteins and 4 HIV-1 proteins were quantified, with 145 proteins changing significantly during the time course. Changes in the proteome peaked 24 h after infection, concomitantly with significant HIV-1 protein production. In the in vivo branch of the study, CD4+ T cells from viremic patients and those with no detectable viral load after treatment were sorted, and the proteomes were quantified. We consistently detected 895 proteins, 172 of which were considered to be significantly different between the viremic patients and patients undergoing successful treatment. The proteome of the in vitro-infected CD4+ T cells was modulated on multiple functional levels, including TLR-4 signaling and the type 1 interferon signaling pathway. Perturbations in the type 1 interferon signaling pathway were recapitulated in CD4+ T cells from patients. The study shows that proteome maps generated by SWATH-MS indicate a range of functionally significant changes in the proteome of HIV-infected human CD4+ T cells. Exploring these perturbations in more detail may help identify new targets for immune based interventions.

Die Phase der HIV-Primoinfektion umfasst den Zeitraum der ersten drei bis sechs Monate nach Infektion. Phylogenetische Analysen des Virus weisen darauf hin, dass bis zu 50 % der Neuinfektionen durch die Übertragung von HIV von Patienten mit einer Primoinfektion zustande kommen. Die Primoinfektion manifestiert sich in 25 – 90% als akutes retrovirales Syndrom. Die häufigsten Symptome sind Fieber, Abgeschlagenheit, Halsschmerzen, Hautausschlag, Lymphknotenschwellung und Durchfall. Allerdings sind diese Symptome zu unspezifisch, um eine Primoinfektion klinisch sicher diagnostizieren zu können. In einer bedeutenden Anzahl der Fälle kann sich die Primoinfektion asymptomatisch, symptomarm oder atypisch präsentieren, so dass bei Personen mit Risiko niederschwellig ein HIV-Test veranlasst werden soll. Die heute routinemäßig verwendeten HIV-Suchtests der 4. Generation vermögen eine Primoinfektion in den meisten Fällen nach ca. zwei bis drei Wochen zu detektieren, der routinemäßige Einsatz einer HIV-PCR wird in der Praxis nicht als Suchtest empfohlen. Die aktuelle Datenlage weist darauf hin, dass eine antiretrovirale Frühtherapie den Krankheitsverlauf günstig beeinflussen kann und zusätzlich hilft, weitere Infektionen zu vermeiden. Die Frühtherapie wird heutzutage von den meisten internationalen Fachgremien empfohlen. Eine Frühtherapie sollte durch mit HIV erfahrene Ärzte initiiert werden.

Approximately 9 million cases of tuberculosis (TB) are reported annually and half a million occur in children

Summary Background Worldwide, the burden of multidrug-resistant bacteria (MDR) is increasing, especially in the hospital setting. Aim To explore characteristics and clinical relevance of MDR obtained from travellers transferred from hospitals abroad. Methods This retrospective study included patients transferred from hospitals abroad to the University Hospital Zurich, Switzerland, who routinely underwent admission screening for possible colonization with meticillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing bacteria (ESBL) and multidrug-resistant Gram-negative bacteria (MR Gram negative). Findings Forty-six (17%) of 259 subjects were found to be colonized with MDR and nine (3.5%) patients to be infected. Thirty-three (12%) patients were colonized with one bacterial species, 12 (4.6%) with two, and three (1.2%) were colonized with three different bacterial species. In total, 36 ESBL, 21 MR Gram-negative and three MRSA isolates were detected. Escherichia coli ( N = 18, 30%), Klebsiella pneumoniae ( N = 14, 23%) and Acinetobacter baumannii ( N = 14, 23%) were most frequently isolated. The most common sites of detection were skin (97%) and respiratory tract (41%). Being colonized contributed to an increased length of ICU stay [median (range): 8 (1–35) vs 3.5 (1–78) days; P = 0.011]. In-hospital mortality in patients colonized with MDR (10.9%) was higher than in uncolonized patients (2.3%, P = 0.018). Being colonized with MDR was associated with death (adjusted odds ratio: 5.176; 95% confidence interval: 1.325–20.218). Conclusions A substantial proportion of patients transferred from abroad are colonized with MDR, a fact which is associated with poor clinical outcome.

Influenza vaccination programmes are assumed to have a herd effect and protect contacts of vaccinated persons from influenza virus infection. We searched MEDLINE, EMBASE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Global Health and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2014 for studies assessing the protective effect of influenza vaccination vs no vaccination on influenza virus infections in contacts. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using a random-effects model. Of 43,082 screened articles, nine randomised controlled trials (RCTs) and four observational studies were eligible. Among the RCTs, no statistically significant herd effect on the occurrence of influenza in contacts could be found (OR: 0.62; 95% CI: 0.34–1.12). The one RCT conducted in a community setting, however, showed a significant effect (OR: 0.39; 95% CI: 0.26–0.57), as did the observational studies (OR: 0.57; 95% CI: 0.43–0.77). We found only a few studies that quantified the herd effect of vaccination, all studies except one were conducted in children, and the overall evidence was graded as low. The evidence is too limited to conclude in what setting(s) a herd effect may or may not be achieved.

Mycobacterium tuberculosis (MTB)-specific cytokine responses in the peripheral blood and at the site of infection may differ significantly within the same individual, but the under-lying T-cell subset changes are largely unknown. Here, we measured effector and memory T-cell markers on CD4⁺ T cells (CD45RO, cysteine chemokine receptor (CCR)7, and CD27) in peripheral blood and at the site of active tuberculosis (TB). Additionally, T cells were stimulated overnight with purified protein derivative (PPD) and early secretory antigenic target (ESAT)-6 to determine which T-cell subset produces MTB-specific interferon (IFN)-γ. A striking decrease in CCR7 and CD27 expression on T cells was noted at the site of active TB. Likewise, IFN-γ expressing, ESAT-6 specific CD4⁺CD45RO⁺CD27⁻ T cells were dramatically increased at the site of infection but were not detectable in peripheral blood. An antigen-specific expansion of differentiated T cells at the site of active TB infection was poorly reflected in peripheral blood. Insight in these changes in MTB-specific effector T cells in different compartments of the body could lead to new approaches for immune-based diagnosis and interventions.

Interferon-γ release assays (IGRAs) are now established for the immunodiagnosis of latent infection with Mycobacterium tuberculosis in many countries. However, the role of IGRAs for the diagnosis of active tuberculosis (TB) remains unclear. Following preferred reporting items for systematic reviews and meta-analyses (PRISMA) and quality assessment of diagnostic accuracy studies (QUADAS) guidelines, we searched PubMed, EMBASE and Cochrane databases to identify studies published in January 2001-November 2009 that evaluated the evidence of using QuantiFERON-TB® Gold in-tube (QFT-G-IT) and T-SPOT.TB® directly on blood or extrasanguinous specimens for the diagnosis of active TB. The literature search yielded 844 studies and 27 met the inclusion criteria. In blood and extrasanguinous fluids, the pooled sensitivity for the diagnosis of active TB was 80% (95% CI 75-84%) and 48% (95% CI 39-58%) for QFT-G-IT, and 81% (95% CI 78-84%) and 88% (confirmed and unconfirmed cases) (95% CI 82-92%) for T-SPOT.TB®, respectively. In blood and extrasanguinous fluids, the pooled specificity was 79% (95% CI 75-82%) and 82% (95% CI 70-91%) for QFT-G-IT, and 59% (95% CI 56-62%) and 82% (95% CI 78-86%) for T-SPOT.TB®, respectively. Although the diagnostic sensitivities of both IGRAs were higher than that of tuberculin skin tests, it was still not high enough to use as a rule out test for TB. Positive evidence for the use of IGRAs in compartments other than blood will require more independent and carefully designed prospective studies.

OBJECTIVES Antibiotics are commonly classified into bactericidal and bacteriostatic agents based on their antimicrobial action. We aimed to assess whether this distinction is clinically relevant. METHODS OVID MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials (CENTRAL) and relevant references and conference proceedings using the Web of Science and Scopus databases were searched for randomized controlled trials comparing bactericidal with bacteriostatic antibiotics for treatment of severe infections. Main outcome measures were clinical cure rates and overall mortality. Abstracts of studies selected in the database search were screened by one reviewer; full-text screening and data extraction were performed by three independent reviewers. RESULTS Thirty-three studies were included. Approximately half of patients were treated with bacteriostatic monotherapy. Infections covered were pneumonia (n = 13), skin and soft tissue infections (n = 8), intra-abdominal infections (n = 4) and others (n = 8). Neither clinical cure rates [risk ratio (RR), 0.99; 95% CI, 0.97-1.01; P = 0.11] nor mortality rates (RR, 0.91; 95% CI, 0.76-1.08; P = 0.28) were different between patients treated with bactericidal drugs and those treated with bacteriostatic drugs. Subgroup analyses showed a benefit for clinical cure rates associated with linezolid and increased mortality associated with tigecycline. In meta-regression, clinical cure rates remained higher in patients treated with linezolid (P = 0.01); tigecycline displayed a close to significant association with increased mortality (P = 0.05) if compared with other bacteriostatic agents. CONCLUSIONS The categorization of antibiotics into bacteriostatic and bactericidal is unlikely to be relevant in clinical practice if used for abdominal infections, skin and soft tissue infections and pneumonia. Because we were not able to include studies on meningitis, endocarditis or neutropenia, no conclusion regarding these diseases can be drawn.

Als spitalerworbene Pneumonie wird eine Pneumonie bezeichnet, die fruhestens 48 Stunden nach Spitaleintritt auftritt.

Primary HIV-infection (PHI) encompasses the first 6 months after HIV infection. Phylogenetic analysis demonstrates that PHI accounts for approximately half of onward transmissions. Between 25 and 90 % of patients with PHI present with an acute retroviral syndrome, but asymptomatic or atypical manifestations of PHI are substantially underestimated and occur in up to one third. Signs and symptoms include fever, fatigue, sore throat, exanthema, lymphadenopathy and diarrhea. The unspecific nature of these signs and symptoms preclude a reliable clinical diagnosis. Therefore, an HIV test should be performed routinely amongst persons at risk. The 4th generation Combo test detects PHI in most cases within two to three weeks after infection and should be used for screening. A routine use of the HIV-specific PCR for screening purposes is discouraged. During the last decade early antiretroviral therapy has been recognized as beneficial for patients with PHI and therefore is recommended.Die Phase der HIV-Primoinfektion umfasst den Zeitraum der ersten drei bis sechs Monate nach Infektion. Phylogenetische Analysen des Virus weisen darauf hin, dass bis zu 50 % der Neuinfektionen durch die Übertragung von HIV von Patienten mit einer Primoinfektion zustande kommen. Die Primoinfektion manifestiert sich in 25 – 90% als akutes retrovirales Syndrom. Die häufigsten Symptome sind Fieber, Abgeschlagenheit, Halsschmerzen, Hautausschlag, Lymphknotenschwellung und Durchfall. Allerdings sind diese Symptome zu unspezifisch, um eine Primoinfektion klinisch sicher diagnostizieren zu können. In einer bedeutenden Anzahl der Fälle kann sich die Primoinfektion asymptomatisch, symptomarm oder atypisch präsentieren, so dass bei Personen mit Risiko niederschwellig ein HIV-Test veranlasst werden soll. Die heute routinemäßig verwendeten HIV-Suchtests der 4. Generation vermögen eine Primoinfektion in den meisten Fällen nach ca. zwei bis drei Wochen zu detektieren, der routinemäßige Einsatz einer HIV-PCR wird in der Praxis nicht als Suchtest empfohlen. Die aktuelle Datenlage weist darauf hin, dass eine antiretrovirale Frühtherapie den Krankheitsverlauf günstig beeinflussen kann und zusätzlich hilft, weitere Infektionen zu vermeiden. Die Frühtherapie wird heutzutage von den meisten internationalen Fachgremien empfohlen. Eine Frühtherapie sollte durch mit HIV erfahrene Ärzte initiiert werden.

Artemisinins show the potential for neurotoxicity in preclinical studies. Artemisone is a leading candidate of second-generation semi-synthetic artemisinin derivatives for antimalarial therapy devoid of neurotoxicity. Artemisone showed 3-5-fold higher in vitro activity (50% effective concentration (EC50) = 0.14 nmol/L, EC90 = 2.55 nmol/L) than artesunate against fresh Plasmodium falciparum isolates from Gabon and a high-activity correlation indicates a shared drug target.

Underpinned by the accuracy of GNSS technologies the Volumetric Navigation System (VNS) concept introduces the opportunity of working not only with positions for identifying the location of any moving vehicle, but also with the capacity to manage the geo- referenced volume associated to the vehicle. This issue allows a safer navigation and traffic interaction especially in scenarios involving large vehicles in narrow sections. Based on this concept ARIADNA encompasses a new maritime navigation support system in order to allow optimization of the infrastructures, the navigation on dense traffic in ports, rivers, channels, lock and their access areas; developing a system which leads to efficient and environmentally-friendly maritime and inland operations.

This article reports on a 62-year-old man, who presented with cervical mass and rather nonspecific symptoms. The medical history and clinical workup initially favored a malignant disease such as a carcinoma of unknown primary as the underlying cause. Eventually, the patient was diagnosed with a granulomatous lymphadenitis caused by Francisella tularensis subsp holarctica. Tularemia is a rare disease in Western Europe and can present in multiple ways encompassing almost asymptomatic infections and fatal disease. A rapid diagnosis is often hampered by nonspecific symptoms and the generally low prevalence and incidence of this disease in endemic countries. This case report also provides a comprehensive review of the literature on cervical tularemia and discusses the differential diagnoses.