Calculated parenteral initial treatment of bacterial infections: Microbiology.

This is the second chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Preliminary microbiological findings regarding the patient and their immediate environment are crucial for the calculation of treatment with antibiotics in each case, as well as the resistance situation of the ward on which the patient is being cared for. If such data is not available, regional or supra-regional data can be used as a fallback. This chapter describes the methods of susceptibility testing, informs about the resistance situation in Germany and describes the main resistance mechanisms of bacterial pathogens against antibiotics. Further, the chapter informs about collateral damage of antibiotics as well as medical measures against increasing resistance.

Use of MALDI-TOF mass spectrometry to detect nosocomial outbreaks of Serratia marcescens and Citrobacter freundii.

MALDI-TOF mass spectrometry (MS) may be used as a rapid typing method for nosocomial pathogens. Here, we evaluated MALDI-TOF MS for discrimination of hospital outbreak-related clusters of Serratia marcescens and carbapenemase-producing Citrobacter freundii. Thirty-three S. marcescens isolates collected from neonatal intensive care unit (NICU) patients, and 23 C. freundii isolates including VIM-positive isolates from a hospital colonization outbreak were measured by Vitek MS. Consensus spectra of each isolate were clustered using SARAMIS software. Genotyping was performed by whole-genome sequencing (WGS). First, a set of 21 S. marcescens isolates from 2014 with seven genotypes including three monoclonal clusters was used for the evaluation of MALDI-TOF typing. MS clustering was largely in agreement with genotyping results when the similarity cut-off for clonal identity was set on 90%. MALDI-TOF cluster analysis was then investigated for the surveillance of S. marcescens in the NICU in 2017 and demonstrated the introduction of new strains into the hospital and nosocomial transmissions. MS analysis of the C. freundii outbreak in 2016 revealed a monoclonal cluster of VIM-positive isolates and the separation of epidemiologically non-related VIM-positive and negative isolates. Two additional VIM-positive Citrobacter isolates from food samples were closely related to the large monoclonal cluster. WGS confirmed the MS results. MALDI-TOF MS may be used as a first-line typing tool for S. marcescens and C. freundii to detect transmission events in the hospital because isolates of an identical WGS type were grouped into the same MS cluster.

Neuroborreliosis and acute encephalopathy: The use of CXCL13 as a biomarker in CNS manifestations of Lyme borreliosis.

We report the case of an 80-year-old patient with acute onset confusion initially suspected to reflect delirium in incipient Alzheimer's disease. Cerebrospinal fluid tests revealed an unusually severe form of neuroborreliosis, which resolved following antibiotic treatment. This was mirrored in the measurement of CXCL13, which is suggested as a complementary biomarker. Clinical implications for screening, differential diagnosis and treatment are discussed.

Schnelltest-Diagnostik sexuell übertragbarer Infektionen in niedrigschwelligen Einrichtungen : Gemeinsame Stellungnahme des RKI, PEI und der DSTIG.

On February 5th, 2016 an expert meeting on rapid diagnostic tests (RDT) for sexually transmitted infections (STI) was held in Berlin at the Robert-Koch-Institute. The aim of the conference was to update a former evaluation of RDTs for diagnosis of HIV, HBV, HCV, T. pallidum, C. trachomatis and N. gonorrhoeae in low-threshold counseling services for STI that had been published after the previous meeting in 2012. According to the strategy to control HIV, hepatitis B and C and other STI, recently adopted by the German Government, there is a lack of test capabilities and a demand for more testing services as well as improved access to testing. Using RDTs as low-threshold test services in counseling centers or even for testing at home may provide an important option to lower the barrier of testing. Based on performance data evaluated in clinical trials some RDTs for HIV, HCV and syphilis are quite well suited as a point-of-care Test (POCT). In contrast, sufficient diagnostic accuracy for detection of C. trachomatis and N. gonorrhoeae can only be achieved by PCR-based POCTs. In Germany the use of POCTs is subjected to legal stipulations of IfSG and MPG. Of importance, it is not allowed to deliver HIV tests to private persons for home testing (§ 11, MPG). Furthermore, both assessment and communication of infectious diseases are reserved to the physician and must not happen as remote diagnostics (§ 24, IfSG). In addition, like all laboratory tests, RDTs are subject to quality assessment according to guidelines of the German Medical Association.

Draft Genome Sequence of the Vaccination Strain Mycobacterium bovis BCG S4-Jena.

Here, we present the draft genome sequence of ITALIC! Mycobacterium bovisBCG S4-Jena, a tuberculosis vaccine strain. The genome of S4-Jena is represented by 48 scaffolds, consisting of 132 scaffolded contigs and amounting to a size of about 4.2 Mb. New genes potentially encoding a phage fragment were identified in the genome.

Severe leptospirosis complicated by Epstein-Barr Virus reactivation.

INTRODUCTION: Weil's disease is a severe, potentially fatal illness following Leptospira interrogans infection. The reported case of a patient suffering from acute renal failure, jaundice, thrombocytopenia, rhabdomyolysis and encephalitis syndrome highlights the clinical challenge in reference to Weil syndrome complicated by Epstein-Barr Virus (EBV) reactivation. MATERIALS AND METHODS: The diagnosis of leptospirosis was performed using four different diagnostic methods. Sera were analyzed with an in-house IgM and IgG enzyme-linked immunosorbent assay (ELISA) and indirect haemagglutination assay (IHA). Microscopic agglutination test (MAT) was done using 17 reference strains comprising 14 serogroups and 17 serovars. Polyvalent EBV-IgG analysis, EBV-IgG/IgM/IgA western blot analysis as well as quantitative EBV polymerase chain reaction (PCR) were performed. RESULTS: Leptospira IHA showed an initial titer of 1:640 (cut-off 1:320), leptospiral IgG was negative, but IgM was positive. MAT was negative at that time for all 17 strains analyzed. One week later, leptospirosis IHA titer increased to 1:20,480. Leptospiral IgG was now positive, -IgM remained positive and urine was tested negative for leptospiral DNA. The MAT showed positive results for L. interrogans serovar Bataviae, serovar Copenhageni, serovar Pyrogenes and L. borgpetersenii serovar Serjoe. During follow-up examinations, both the leptospiral IgM and IgG remained positive and MAT showed positive results for L. interrogans of different serovars. EBV IgA immunoblot taken at admission was positive for VCA-p18, quantitative EBV-PCR showed an EBV viral load of 2.8E3 copies/ml indicating acute EBV-reactivation. CONCLUSION: Leptospirosis represents a neglected and re-emerging disease which is difficult to diagnose since Leptospira-PCR from whole blood or urine is frequently negative in the case of early empiric antibiotic treatment. EBV-reactivation might represent a severe complication in Weil's disease which potentially aggravates clinical manifestations of leptospirosis including hepatitis, nephritis, and rhabdomyolysis. Thus, there might be a need for peripheral blood EBV-PCR and EBV blotting in patients suffering from complicated Weil syndrome, also in terms of the choice of antibiotic treatment.

Detection of pneumonia associated pathogens using a prototype multiplexed pneumonia test in hospitalized patients with severe pneumonia.

UNLABELLED: Severe pneumonia remains an important cause of morbidity and mortality. Polymerase chain reaction (PCR) has been shown to be more sensitive than current standard microbiological methods--particularly in patients with prior antibiotic treatment--and therefore, may improve the accuracy of microbiological diagnosis for hospitalized patients with pneumonia. Conventional detection techniques and multiplex PCR for 14 typical bacterial pneumonia-associated pathogens were performed on respiratory samples collected from adult hospitalized patients enrolled in a prospective multi-center study. Patients were enrolled from March until September 2012. A total of 739 fresh, native samples were eligible for analysis, of which 75 were sputa, 421 aspirates, and 234 bronchial lavages. 276 pathogens were detected by microbiology for which a valid PCR result was generated (positive or negative detection result by Curetis prototype system). Among these, 120 were identified by the prototype assay, 50 pathogens were not detected. Overall performance of the prototype for pathogen identification was 70.6% sensitivity (95% confidence interval (CI) lower bound: 63.3%, upper bound: 76.9%) and 95.2% specificity (95% CI lower bound: 94.6%, upper bound: 95.7%). Based on the study results, device cut-off settings were adjusted for future series production. The overall performance with the settings of the CE series production devices was 78.7% sensitivity (95% CI lower bound: 72.1%) and 96.6% specificity (95% CI lower bound: 96.1%). Time to result was 5.2 hours (median) for the prototype test and 43.5 h for standard-of-care. The Pneumonia Application provides a rapid and moderately sensitive assay for the detection of pneumonia-causing pathogens with minimal hands-on time. TRIAL REGISTRATION: Deutsches Register Klinischer Studien (DRKS) DRKS00005684.

Preoperative serum pattern analysis to predict the outcome of tonsillectomy in adults with chronic tonsillitis.

The method of classification and tree analysis (CART) was used to predict the outcome of tonsillectomy for chronic tonsillitis (CHT) analyzing patterns of serological markers. In a prospective case study of 24 adult patients with CHT in comparison to 24 patients with acute peritonsillar abscess (PTA) blood samples were assessed 1 day before (T-1) and 3 days after tonsillectomy. Outcome 6 months later (T180) was documented using the Glasgow Benefit Inventory (GBI) and the Specific Benefits from Tonsillectomy Inventory (SBTI). In comparison to PTA, patients with CHT were at best classified by C-reactive protein with a cut-off value of <16.735 mg/dl. For CHT, immunoglobulin E ≤ 144.65 kU/l and the combination of monocytes ≤ 0.565 Gpt/l plus leucocytes >5.855 Gpt/l at T-1 were the best classificators for higher SBTI overall score and symptom score symptom score, respectively, at T180. A higher benefit subscore at T180 was associated to γ-globulin >15.85 % plus α2-globulin >8.950% at T-1. The best classificator for better GBI overall score at T180 was an ASL titer >169.0 IU/ml or the combination of an ASL titer ≤ 169.0 IU/ml with lymphocytes ≤ 2.195 Gpt/l. Lymphocytes ≤ 2.195 Gpt/l were associated with higher GBI general subscore. Leukocytes ≤ 6.780 Gpt/l were related to higher GBI social support subscore. The combination of immunoglobulin A >1.360 g/l with procalcitonin level >0.058 ng/ml was the best combination to classify for higher physical health score. Instead of looking on isolated serologic markers, CART of multiple parameters seems to be more effective to predict the outcome of tonsillectomy for CHT.

Specific risk factors for contracting Q fever: lessons from the outbreak Jena.

A Q fever outbreak with 331 reported cases in seven weeks occurred in a densely populated residential district in Jena (Germany) in 2005. Prompt identification of a stable infection source follow by an intense information policy, well defined and stable meteorological conditions and a large number of reported cases within one small community all allowed us to study promoting and protecting factors of Q fever. We conducted a cross-sectional study and investigated a part of the affected area for 100% sampling (in-home interviews). Out of 608 residents at home 460 (75.7%) participated in the study and 101 fulfilled our definition of an acute Q fever case. Our data revealed a critical zone for residency within 500 m of herds of gestating ewes in a typical urban dwelling area. We found an association between shift work and contracting Q fever. An association between outdoor activity and Q fever was only found after prolonged outdoor stays, on average more than 4h/day. Only open windows facing the putative source were associated with increased risk of Q fever. Therefore fully open windows of more than 6h/day is a significant parameter.

Culture independent Raman spectroscopic identification of urinary tract infection pathogens: a proof of principle study.

Urinary tract infection (UTI) is a very common infection. Up to every second woman will experience at least one UTI episode during her lifetime. The gold standard for identifying the infectious microorganisms is the urine culture. However, culture methods are time-consuming and need at least 24 h until the results are available. Here, we report about a culture independent identification procedure by using Raman microspectroscopy in combination with innovative chemometrics. We investigated, for the first time directly, urine samples by Raman microspectroscopy on a single-cell level. In a first step, a database of eleven important UTI bacterial species, which were grown in sterile filtered urine, was built up. A support vector machine (SVM) was used to generate a statistical model, which allows a classification of this data set with an accuracy of 92% on a species level. This model was afterward used to identify infected urine samples of ten patients directly without a preceding culture step. Thereby, we were able to determine the predominant bacterial species (seven Escherichia coli and three Enterococcus faecalis ) for all ten patient samples. These results demonstrate that Raman microspectroscopy in combination with support vector machines allow an identification of important UTI bacteria within two hours without the need of a culture step.

Clinical significance and diagnostic usefulness of serologic markers for improvement of outcome of tonsillectomy in adults with chronic tonsillitis.

BACKGROUND: The aim of the present study was to explore serological biomarkers which predict the outcome of tonsillectomy for chronic tonsillitis. METHODS: A case study in a University ENT department of 24 adult patients with chronic tonsillitis (CHT) in comparison to 24 patients with acute peritonsillar abscess (PTA) was performed. Blood samples for clinical routine hematological and serological parameters were assessed prior to surgery (T-1) and five days (T5) after tonsillectomy. Outcome 6 months later (T180) was documented using the Glasgow Benefit Inventory (GBI) and the Specific Benefits from Tonsillectomy Inventory (SBTI). Correlation analyses between CHT and PTA group as well as between the different time points within each group concerning the serological parameters and the outcome parameters were performed. RESULTS: At T-1, patients in the CHT group presented with significantly higher lymphocytes counts (relative and absolute), basophils (relative and absolute) and eosinophils but less white-cells, monocytes, neutrophils (absolute and relative), alpha-1, alpha-2, beta globulins, immunoglobulin and lower C-reactive protein and procalcitonin values than patients in the PTA group (all p < 0.05, respectively). Within each group, different significant changes of the serum parameters (often in opposite direction) were observed between T-1 and T5. SBTI scores at T-1 were significantly lower in the CHT group. In contrast, most GBI scores at T180 were significantly higher in the CHT group. Between T-1 and T180 the SBTI scores improved in three quarters of the CHT patients but only in three fifths of the PTA patients. Higher eosinophil counts and immunoglobulin E levels at T-1 predicted higher GBI scores at T180 in the CHT group. CONCLUSIONS: This pilot study showed a specific serological pattern for patients with chronic tonsillitis with a specific pattern of changes after tonsillectomy. But there is no established role for biomarkers currently used in clinical practice to predict the outcome of tonsillectomy for chronic tonsillitis.

Attributable costs of patients with candidemia and potential implications of polymerase chain reaction-based pathogen detection on antifungal therapy in patients with sepsis.

PURPOSE: The purposes of this study were to calculate attributable costs of candidemia in patients with severe sepsis and to obtain preliminary data regarding the potential effects of polymerase chain reaction-based pathogen detection on antifungal therapy for these patients. METHODS: Patients treated between 2004 and 2010 because of severe sepsis were included into this retrospective analysis. The hospital management provided annual fixed costs per patient-day; data for variable intensive care unit costs were taken from the literature. Multiplex polymerase chain reaction (PCR) was used (VYOO, SIRS-Lab, Jena, Germany) for pathogen detection in the blood. RESULTS: Thirty-two patients with candidemia were identified. Of 874 patients with sepsis, propensity score matching found 32 corresponding patients with sepsis but without candida infection but similar risk factors for developing candidemia. Attributable costs of candidemia were 7713.79 Euro (cost increase, 19.4%). Initiation of antifungal therapy was reduced from 67.5 (52.4, 90) hours in the group, where candida infection was determined by blood culture, to 31.0 (28.0, 37.5; P < .01) hours after detection by multiplex PCR. CONCLUSIONS: Candidemia increases costs of care in patients with septic shock. Polymerase chain reaction-based pathogen detection significantly reduces the time to initiation of antifungal therapy. This might impact on the clinical course of the disease but need to be confirmed in further trials.

Maternofetal consequences of Coxiella burnetii infection in pregnancy: a case series of two outbreaks.

BACKGROUND: A high complication rate of Q fever in pregnancy is described on the basis of a limited number of cases. All pregnant women with proven Q fever regardless of clinical symptoms should therefore receive long-term cotrimoxazole therapy. But cotrimoxazole as a folic acid antagonist may cause harm to the fetus. We therefore investigated the Q fever outbreaks, Soest in 2003 and Jena in 2005, to determine the maternofetal consequences of Coxiella burnetii infection contracted during pregnancy. METHODS: Different outbreak investigation strategies were employed at the two sides. Antibody screening was performed with an indirect immunofluorescence test. Medical history and clinical data were obtained and serological follow up performed at delivery. Available placental tissue, amniotic fluid and colostrum/milk were further investigated by polymerase chain reaction and by culture. RESULTS: 11 pregnant women from Soest (screening rate: 49%) and 82 pregnant women from Jena (screening rate: 27%) participated in the outbreak investigation. 11 pregnant women with an acute C. burnetii infection were diagnosed. Three women had symptomatic disease. Three women, who were infected in the first trimester, were put on long-term therapy. The remaining women received cotrimoxazole to a lesser extent (n=3), were treated with macrolides for three weeks (n=1) or after delivery (n=1), were given no treatment at all (n=2) or received antibiotics ineffective for Q fever (n=1). One woman and her foetus died of an underlying disease not related to Q fever. One woman delivered prematurely (35th week) and one child was born with syndactyly. We found no obvious association between C. burnetii infection and negative pregnancy outcome. CONCLUSIONS: Our data do not support the general recommendation of long-term cotrimoxazole treatment for Q fever infection in pregnancy. Pregnant women with symptomatic C. burnetii infections and with chronic Q fever should be treated. The risk-benefit ratio of treatment in these patients, however, remains uncertain. If cotrimoxazole is administered, folinic acid has to be added.

Evaluation of a polymerase chain reaction assay for pathogen detection in septic patients under routine condition: an observational study.

BACKGROUND: Treatment of septic shock relies on appropriate antimicrobial therapy. Current culture based methods deliver final results after days, which may delay potentially lifesaving adjustments in antimicrobial therapy. This study was undertaken to compare PCR with blood culture results under routine conditions regarding 1. impact on antimicrobial therapy, and 2. time to result, in patients with presumed sepsis. METHODOLOGY/PRINCIPAL FINDINGS: This was an observational study in a 50 beds ICU of a university hospital. In 245 patients with suspected sepsis, 311 concomitant blood cultures and blood for multiplex PCR (VYOO(®)) were obtained. 45 of 311 blood cultures (14.5%) and 94 of 311 PCRs (30.1%) were positive. However, blood culture or microbiological sampling from the presumed site of infection rarely confirmed PCR results and vice versa. Median time to positivity and interquartile range were 24.2 (18.0, 27.5) hours for the PCR and 68 (52.2, 88.5) hours for BC (p<0.01). PCR median time to result was dependent on technician availability (53.5 hours on Saturdays, 7.2 hours under optimal logistic conditions). PCR results showed good correlation with procalcitonin (p<0.001). In 34% of patients with positive PCRs antimicrobial therapy was considered inadequate according to assessment of clinical arbitrators including 5 patients with vancomycin-resistant enterococci (VRE), 3 cases with multiresistant staphylococci, and 4 patients with fungi. CONCLUSIONS: The results of this observational study support the hypothesis that PCR results are available faster, are more frequently positive, and may result in earlier adjustment of antimicrobial therapy. However, shorter time to result can only be fully exploited when the laboratory is adequately staffed for a 24 hour/7 day service, or when point of care/automated assay systems become available.

Prevalence of hepatitis E virus-specific antibodies in humans with occupational exposure to pigs.

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.

Persistent Chlamydia trachomatis infection of HeLa cells mediates apoptosis resistance through a Chlamydia protease-like activity factor-independent mechanism and induces high mobility group box 1 release.

Intracellular persistence of Chlamydia trachomatis has been implicated in the development of chronic infection that can result in pelvic inflammatory disease and tubal sterility. By inhibition of host cell apoptosis, chlamydiae have evolved a strategy to maintain the intracellular environment for replication and persistence. Both antiapoptotic host cell-derived factors and the chlamydial protease-like activity factor (CPAF) are involved in Chlamydia-mediated apoptosis resistance. Here, we show that in HeLa cells infected with gamma interferon (IFN-γ)-induced persistent C. trachomatis serovar D, the expression of CPAF is downregulated, and proapoptotic protease substrates are not cleaved. Persistent infection protected HeLa cells from apoptosis when they were exposed to staurosporine. Small-interfering RNA-mediated inhibition of myeloid cell leukemia 1 (Mcl-1) protein upregulation sensitized persistently infected cells for apoptosis. The inhibitor of apoptosis protein 2 (IAP-2) seems not to be relevant in this context because IAP-2 protein was not induced in response to IFN-γ treatment. Although apoptosis was inhibited, persistent infection caused cell membrane disintegration, as measured by the increased release of cytokeratin 18 from HeLa cells. Moreover, persistently infected cells released significantly increased amounts of high mobility group box 1 (HMGB1) protein which represents a proinflammatory damage-associated pattern molecule. The data of this study suggest that cells infected with persistent C. trachomatis are protected from apoptosis independently of CPAF but may promote chronic inflammation through HMGB1 release.

Supra-additive expression of interleukin-6, interleukin-8 and basic fibroblast growth factor in vascular smooth muscle cells following coinfection with Chlamydia pneumoniae and cytomegalovirus as a novel link between infection and atherosclerosis.

BACKGROUND: Chlamydia pneumoniae and human cytomegalovirus (HCMV) may be involved in the pathogenesis of atherosclerosis. Prospective studies indicate an increased risk for cardiovascular events in patients with evidence of multiple infections. OBJECTIVE: To determine whether there is a synergistic effect of coinfection with C pneumoniae and HCMV on expression of selected growth factors and cytokines. METHODS: The production of interleukin (IL)-6, IL-8, basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF), and 'regulated on activation normal T-cell expressed and secreted' (RANTES) was measured in coinfected aortic smooth muscle cells (AoSMC). RESULTS: Using reverse transcription polymerase chain reaction and immunoassays, it was demonstrated that the expression of IL-6, IL-8, RANTES and bFGF was stimulated in a dose- and time-dependent fashion in C pneumoniae and also in HCMV-infected cultures. In contrast, the expression of PDGF-AA was only stimulated following HCMV infection. Coinfection with C pneumoniae and HCMV resulted in a supra-additive stimulation of IL-6 (30% increased expression, P≤0.05) at 48 h, IL-8 (137% increased expression, P≤0.001) at 24 h and bFGF (209% increased expression, P≤0.01) at 48 h following infection. CONCLUSIONS: The findings of the present study show that C pneumoniae and HCMV are able to act in synergy in coinfected AoSMC. The supra-additive induction of AoSMC growth factors and cytokines indicates a novel molecular link between infection and vascular disease development.

HISTORIQUE: Le Chlamydia pneumoniae et le cytomégalovirus humain (CMVH) participent peut-être à la pathogenèse de l'athérosclérose. Selon des études prospectives, le risque d'événements cardiovasculaires est plus important chez les patients présentant des manifestations d'infections multiples. OBJECTIF: Déterminer si la co-infection par le C pneumoniae et le CMVH a un effet synergétique sur l'expression de facteurs de croissance et de cytokines précises. MÉTHODOLOGIE: Les chercheurs ont mesuré la production d'interleukine (IL)-6, d'IL-8, du facteur de croissance basique des fibroblastes (FCbF), du facteur de croissance dérivé des plaquettes (FCDP) et de la protéine RANTES régulée à l'activation, exprimée par les lymphocytes T normaux et sécrétée en présence de co-infection des cellules des muscles lisses de l'aorte (CMLA). RÉSULTATS: Au moyen de la réaction en chaîne de la polymérase à transcription inverse et du dosage immunologique, les chercheurs ont démontré que l'expression de l'IL-6, de l'IL-8, de la protéine RANTES et du FCbF étaient stimulés selon la dose et le délai dans les cellules infectées par le C pneumoniae ainsi que par le CMVH. Par contre, l'expression du FCDP-AA n'était stimulée qu'après une infection par le CMVH. Une co-infection par le C pneumoniae et le CMVH entraînait une stimulation supra-additive de l'IL-6 (expression accrue de 30 %, P≤0,05) 48 heures après l'infection, de l'IL-8 (expression accrue de 137 %, P≤0,001) 24 heures après l'infection et du FCbF (expression accrue de 209 %, P≤0,01) 48 heures après l'infection. CONCLUSIONS: Les résultats de la présente étude démontrent que le C pneumoniae et le CMVH peuvent agir en synergie en cas de co-infection des CMLA. L'induction supra-additive des facteurs de croissance des CMLA et des cytokines laisse supposer un nouveau lien moléculaire entre l'infection et l'apparition d'une maladie vasculaire.

Human cytomegalovirus induces MMP-1 and MMP-3 expression in aortic smooth muscle cells.

Human cytomegalovirus (HCMV) infection may be involved in the pathogenesis of atherosclerosis by modulating functions of smooth muscle cells (SMC). In this study, we performed an oligonucleotide microarray screening of 780 inflammation-associated genes in HCMV-infected aortic SMC (AoSMC). The expression of 31 genes was stimulated and 24 genes were down-regulated following infection with HCMV strain DC-134. Following infection with HCMV strain AD-169 infection, we found 24 genes to be stimulated and 32 genes to be down-regulated. Among these were primarily genes encoding for CC and CXC chemokines, adhesion molecules, and tumor necrosis factor (TNF) receptor superfamily members, apoptosis-related factors, signal transduction molecules and transcription regulators. The up-regulated genes included matrix metalloproteinase (MMP)-1 and MMP-3 in HCMV infected cells. Using RT-PCR and enzyme immunoassay we found stimulated expression of MMP-1 (3.2-fold expression) and MMP-3 (334-fold expression) in HCMV strain DC-134-infected AoSMC at 72 h following infection.The findings of our study suggest that HCMV infection of AoSMC cause an activation of atherosclerosis-relevant factors in SMC. The increased expression of MMPs which have been shown to be involved in atherosclerotic plaque rupture and myocardial infarction is in agreement with the hypothesis that this pathogen might contribute to plaque inflammation in atherosclerotic disease.

Diversity and coexistence of tick-borne pathogens in central Germany.

In total, 1000 Ixodes ricinus L. ticks were collected from a small recreational forest area in central Germany (Thuringia) and investigated for the presence of Borrelia spp., Babesia spp., Anaplasma spp., Rickettsia spp., Coxiella burnetii, and Francisella tularensis. Overall, 43.6% of the ticks were infected with at least one pathogen. In 8.4% of ticks double infections were detected, and 1.6% harbored more than two pathogens. In this study, we present data on the coexistence of established and emerging pathogens in questing nymphs and adult ticks in a recreational area in central Germany, indicating the need for further studies for a reliable risk assessment.