Potential Role for Urine Polymerase Chain Reaction in the Diagnosis of Whipple's Disease.

BACKGROUND: Whipple's disease (WD) is a rare infection with Tropheryma whipplei that is fatal if untreated. Diagnosis is challenging and currently based on invasive sampling. In a case of WD diagnosed from a kidney biopsy, we observed morphologically-intact bacteria within the glomerular capsular space and tubular lumens. This raised the questions of whether renal filtration of bacteria is common in WD and whether polymerase chain reaction (PCR) testing of urine might serve as a diagnostic test for WD. METHODS: We prospectively investigated urine samples of 12 newly-diagnosed and 31 treated WD patients by PCR. As controls, we investigated samples from 110 healthy volunteers and patients with excluded WD or acute gastroenteritis. RESULTS: Out of 12 urine samples from independent, therapy-naive WD patients, 9 were positive for T. whipplei PCR. In 3 patients, fluorescence in situ hybridization visualized T. whipplei in urine. All control samples were negative, including those of 11 healthy carriers with T. whipplei-positive stool samples. In our study, the detection of T. whipplei in the urine of untreated patients correlated in all cases with WD. CONCLUSIONS: T. whipplei is detectable by PCR in the urine of the majority of therapy-naive WD patients. With a low prevalence but far-reaching consequences upon diagnosis, invasive sampling for WD is mandatory and must be based on a strong suspicion. Urine testing could prevent patients from being undiagnosed for years. Urine may serve as a novel, easy-to-obtain specimen for guiding the initial diagnosis of WD, in particular in patients with extra-intestinal WD.

Chlamydia trachomatis inhibits telomeric DNA damage signaling via transient hTERT upregulation.

Epidemiological data exist to support a positive association between Chlamydia trachomatis (Ctr) infection and gynecological cancers; however, putative cellular mechanisms for this association are lacking. Here, we identified Ctr-induced perturbations to host cell phenotypes in vitro that persisted after clearance of infection and could directly contribute to host cell transformation. In particular, human telomerase catalytic subunit (hTERT) mRNA expression and catalytic subunit activity were increased in acute infected late passage IMR90E1A cells. hTERT upregulation was accompanied by recruitment of ceramide, a known regulator of hTERT, to the chlamydial inclusion and was abrogated following doxycycline-mediated infection clearance. In cells cleared of Ctr infection, average telomere length was slightly increased and immunofluorescence staining of the DNA damage marker γH2A.X was reduced after clearance of infection compared with cells that had not been infected. Reduced p53 binding to the promoter of the cell cycle checkpoint regulator p21 was also detected in cells cleared of infection and p21 levels were reduced; moreover, this cell population exhibited increased resistance to etoposide-induced DNA damage. Thus, Ctr infection altered cell aging and survival pathways, which persisted after infection clearance. Cells that survive infection are likely to exhibit altered physiology, as evidenced by an increased resistance to DNA damage-induced apoptosis, which may support cellular transformation.

[Invasive meningococcal disease: increased risk and vaccination prevention for immunocompromised patients]. / Invasive Meningokokken-Erkrankungen : Erhöhtes Risiko und Impfprävention für immunsupprimierte Patientinnen und Patienten.

BACKGROUND: The development of evidence-based guidelines for the prevention of infectious diseases through vaccination requires an understanding of populations that most likely may obtain an infection, severe illness or disease. Targeted vaccination recommendations are made possible by identifying risk groups, as is the case with meningococcal infections. Despite falling case numbers, meningococcal sepsis and meningococcal meningitis remain a major health problem. METHOD: A systematic literature search was carried out on the research platform Ovid. RESULTS: Vulnerable groups of people whose immune system is limited by primary and secondary immunodeficiency, such as asplenia, renal failure, human immunodeficiency virus (HIV) infection, diabetes, complement deficiency, organ and stem cell transplants, or immunomodulatory therapy (e.g., in rheumatic, hematological or oncological diseases), are exposed to an increased risk of infection and more severe courses of disease. Despite adequate medical care, the mortality rate is high and patients that survived the infection are often suffering from severe long-term sequelae. In such cases, the vaccination recommendations of the Standing Committee on Vaccination (STIKO) for indication vaccinations and the application instructions for vaccination in the case of immune deficiency should be consistently implemented in Germany. CONCLUSIONS: Increased responsibility for comprehensive protection must be assumed for persons with underlying diseases. Reducing invasive meningococcal infections can be achieved through widespread education of patients and contacts, as well as practicing physicians on available vaccinations.

Clinical and economic burden of invasive meningococcal disease: Evidence from a large German claims database.

BACKGROUND: Limited data is available to describe clinical characteristics, long-term outcomes, healthcare resource use and the attributable costs of invasive meningococcal disease (IMD) in Germany. We aimed to examine demographic and clinical characteristics as well as healthcare resource use and related costs. METHODS: We conducted a retrospective cohort study based on the InGef database in patients with IMD between 2009 and 2015. Cases were identified based on hospital main discharge diagnoses of IMD. Demographics, clinical characteristics, 30-day and 1-year mortality as well as IMD-related complications and sequelae in IMD cases were examined. In addition, short and long-term costs and healthcare resource use in IMD cases were analyzed and compared to an age- and sex-matched control group without IMD. RESULTS: The study population comprised 164 IMD cases between 2009 and 2015. The mean length of the IMD-related hospitalization was 13 days and 38% of all cases presented with meningitis only, 35% with sepsis only, 16% with both and 11% with other IMD. The 30-day and one-year mortality were 4.3% and 5.5%, respectively. Approximately 13% of IMD cases had documented IMD-related complications at hospital discharge and 24% suffered from sequelae during follow-up. The IMD-related hospitalization was associated with mean costs of € 9,620 (standard deviation: € 22,197). The difference of mean costs between IMD cases and matched non-IMD controls were € 267 in the first month and € 1,161 from one month to one year after discharged from IMD-related hospitalization. During the later follow-up period, the mean overall costs and costs associated with individual healthcare sectors were also higher for IMD cases without reaching statistical significance. CONCLUSIONS: IMD resulted in severe complications and sequelae and was associated with extensive costs and increased healthcare resource use in Germany, especially in the first year after IMD diagnosis and due the IMD-related hospitalization.

Helicobacter pylori-induced modification of the histone H3 phosphorylation status in gastric epithelial cells reflects its impact on cell cycle regulation.

Post-translational modifications of core histones are important components of the epigenetic landscape. Recent investigations of bacterial or toxin-induced effects on histone phosphorylation and acetylation in host cells have linked the changes to transcriptional alterations of key cellular response pathways. However, these changes may have other reasons and functional consequences. Here, we show that infection of gastric epithelial cell lines with the carcinogenic bacterium Helicobacter pylori leads to changes in histone H3 phosphorylation: type IV secretion system (T4SS)-dependent decreases of H3 phosphorylation levels at serine 10 (pH3Ser10) and threonine 3 (pH3Thr3) were observed. Immunofluorescence experiments with pH3Ser10 and cyclin B1 revealed that a H. pylori-induced transient pre-mitotic arrest was responsible for the observed reduction. This causal link was substantiated further by showing that H. pylori causes a strong decrease of the cell division cycle 25 (CDC25C) phosphatase. As a consequence, mitotic histone H3 kinases such as vaccinia-related kinase 1 (VRK1) and Aurora B were not fully activated in infected cells. We show that VRK1 activity, measured using a kinase activity assay, was reduced after H. pylori infection by approximately 40%. Moreover, overexpression of VRK1, but not Aurora B, compensated for the H. pylori-induced decrease of pH3Ser10. Rephosphorylation of H3Ser10 was IkappaB kinase alpha (IKKalpha)-dependent and occurred at later time points of infection. Taken together, our work highlights the impact of bacterial pathogens on host cell chromatin; this modulation reflects the subversion of key cellular processes such as cell cycle progression.