Search

Clostridioides difficile infection (CDI) often manifests as diarrhea, particularly in adults of older age or with underlying comorbidities. However, only severe cases are notifiable in Germany. Moreover, failure to collect a stool specimen from inpatients with diarrhea or incomplete testing may lead to underdiagnosis and underreporting of CDI. We assessed the frequency of diarrhea, stool specimen collection, and CDI testing to estimate CDI underdiagnosis and underreporting among hospitalized adults. In a ten-day point-prevalence study (2019–2021) of nine hospitals in a defined area (Muenster/Coesfeld, North Rhine-Westphalia, Germany), all diarrhea cases (≥ 3 loose stools in 24 h) among adult inpatients were captured via medical record screening and nurse interviews. Patient characteristics, symptom onset, putative origin, antibiotic consumption, and diagnostic stool sampling were collected in a case report form (CRF). Diagnostic results were retrieved from the respective hospital laboratories. Among 6998 patients screened, 476 (7%) diarrhea patients were identified, yielding a hospital-based incidence of 201 cases per 10,000 patient-days. Of the diarrheal patients, 186 (39%) had a stool sample collected, of which 160 (86%) were tested for CDI, meaning that the overall CDI testing rate among diarrhea patients was 34%. Toxigenic C. difficile was detected in 18 (11%) of the tested samples. The frequency of stool specimen collection and CDI testing among hospitalized diarrhea patients was suboptimal. Thus, CDI incidence in Germany is likely underestimated. To assess the complete burden of CDI in German hospitals, further investigations are needed.

Background Coronavirus disease 2019 (COVID-19) is a life-threatening respiratory condition caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and was initially detected in China in December 2019. Currently, in Germany >140 000 cases of COVID-19 are confirmed. Here we report a nosocomial outbreak of SARS-CoV-2 infections in the pediatric dialysis unit of the University Hospital Münster (UHM). Methods Single-step real-time reverse-transcription polymerase chain reaction (rRT-PCR) from nasopharyngeal swabs was used to diagnose the index patient and identify infected contacts. Epidemiological links were analyzed by patient interviews and medical record reviews. In addition, each contact was assessed for exposure to the index case and monitored for clinical symptoms. Cycle threshold (Ct) values of all positive test results were compared between symptomatic and asymptomatic cases. Results Forty-eight cases were involved in this nosocomial outbreak. Nine contact cases developed laboratory-confirmed COVID-19 infections. Two SARS-CoV-2–positive cases remained clinically asymptomatic. Eleven cases reported flulike symptoms without positive results. Ct values were significantly lower in cases presenting typical COVID-19 symptoms, suggesting high viral shedding (P = .007). Conclusions Person-to-person transmission was at the heart of a hospital outbreak of SARS-CoV-2 between healthcare workers (HCWs) and patients in the pediatric dialysis unit at UHM. Semiquantitative rRT-PCR results suggest that individuals with high viral load pose a risk to spread SARS-CoV-2 in the hospital setting. Our epidemiological observation highlights the need to develop strategies to trace and monitor SARS-CoV-2–infected HCWs to prevent COVID-19 outbreaks in the hospital setting.

Staphylococcus aureus is a widely distributed, opportunistic pathogen and has been linked to the human skin disease atopic dermatitis (AD). Here, we present 44 complete and 4 draft genome sequences of S. aureus strains isolated from the nose and skin of AD patients and healthy controls from a German study cohort.

Aim: To estimate the burden of parenting and caregiving duties among clinical microbiologists in Germany and to identify workplace-related support systems and barriers to engaging in career-relevant activities. Methods: A cross-sectional web-based survey was conducted. Participants were asked to answer 37 questions, of which 24 specifically addressed parenting and caregiving duties. Results: Only few workplace-related support systems are currently available, and experiences of job-related disadvantages were frequently reported (27 of 47; 57.4%). Main barriers were a lack of flexible working hours and reliable childcare. Sociocultural norms and a lack of role models were perceived as detrimental. Conclusion: More support systems and a credible culture of family friendliness are needed to prevent jeopardizing the academic potential of young parents.

Over the last few decades, allergic diseases have been steadily increasing worldwide, a phenomenon that is not yet completely understood. Recent evidence, however, suggests that alterations in the microbiome may be a contributing factor. The microbiome refers to all microorganisms in a habitat including bacteria, fungi, and viruses. Using modern sequencing technologies, we are now capable of detecting and analyzing the human microbiome in more detail than ever before. Epidemiological and experimental studies have indicated that a complex intestinal microbiome supports the development of the immune system during childhood, thus providing protection from allergic diseases, including food allergy. The microbiome becomes an important part of human physiology and forms dynamic relationships with our various barrier systems. For example, bacterial dysbiosis is a hallmark of atopic eczema and correlates with disease progression. Similarly, the lung and nasopharyngeal microbiome is altered in patients with asthma and allergic rhinitis. While these results are interesting, the underlying mechanisms are still unclear and need to be investigated with functional studies. This review gives a short overview of the terminology and methods used in microbiome research before highlighting results concerning the lung, skin, and intestinal microbiome in allergic diseases.

Background Currently, hospitals have been forced to divert substantial resources to cope with the ongoing coronavirus disease 2019 (COVID-19) pandemic. It is unclear if this situation will affect long-standing infection prevention practices and impact on healthcare associated infections. Here, we report a nosocomial cluster of vancomycin-resistant enterococci (VRE) that occurred on a COVID-19 dedicated intensive care unit (ICU) despite intensified contact precautions during the current pandemic. Whole genome sequence-based typing (WGS) was used to investigate genetic relatedness of VRE isolates collected from COVID-19 and non-COVID-19 patients during the outbreak and to compare them to environmental VRE samples. Methods Five VRE isolated from patients (three clinical and two screening samples) as well as 11 VRE and six vancomycin susceptible Enterococcus faecium (E. faecium) samples from environmental sites underwent WGS during the outbreak investigation. Isolate relatedness was determined using core genome multilocus sequence typing (cgMLST). Results WGS revealed two genotypic distinct VRE clusters with genetically closely related patient and environmental isolates. The cluster was terminated by enhanced infection control bundle strategies. Conclusions Our results illustrate the importance of continued adherence to infection prevention and control measures during the COVID-19 pandemic to prevent VRE transmission and healthcare associated infections.

During the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, healthcare systems worldwide have to prevent nosocomial SARS-CoV-2 transmission while maintaining duty of care. In our study, we characterize the transmission dynamic of SARS-CoV-2 in inpatients and healthcare workers (HCWs) at the University Hospital Münster (UHM) in northwest Germany. We identified 27 cases of healthcare-associated SARS-CoV-2 infections (4 inpatients and 23 HCWs) who had contact with patients and/or HCWs without the use of adequate PPE. The contacts of these index cases were followed up for SARS-CoV-2 infection after unprotected exposure and a quantitative measure of probability of becoming infected, the attack rate, was calculated. In addition, transmission was evaluated in the context of infection control measures established during the pandemic and we compared the epidemiological data of all index cases, including symptoms and Ct values of virology test results. The overall attack rate in the hospital setting was 1.3% (inpatients 0.9%, HCWs 1.6%). However, during an outbreak, the attack rate was 25.5% (inpatients 20.0%, HCWs 29.6%). For both scenarios, HCWs had a higher attack rate illustrating their role in healthcare-associated SARS-CoV-2 transmission. Taken together, our experiences demonstrate how infection control measures can minimize the transmission of SARS-CoV-2 in the healthcare setting.

Background Transplant recipients are at high risk for infections. However, donor-recipient transmission of multidrug-resistant organisms (MDROs) remains mostly unaddressed in the protocols of pre-transplant infection and colonization screening. Vancomycin-resistant enterococci (VRE) are MDROs that colonize the gastrointestinal tract and are associated with a significant burden of disease. Besides the high mortality of invasive VRE infections, chronic colonization leads to costly isolation measures in the hospital setting. Whereas most post-transplantation VRE infections are endogenous and thus preceded by colonization of the recipient, conclusive evidence of VRE transmission via allograft in the context of intestinal transplantation is lacking. Case presentation We describe a donor-derived VRE infection after intestinal transplantation including small bowel and right hemicolon. The recipient, a 54-year old male with history of mesenteric ischemia and small bowel perforation due to generalized atherosclerosis and chronic stenosis of the celiac trunk and the superior mesenteric artery, developed an intra-abdominal infection and bloodstream infection after transplantation. VRE isolates recovered from the patient as well as from the allograft prior to transplantation were analyzed via whole genome sequencing. Isolates showed to be genetically identical, thus confirming the transmission from donor to recipient. Conclusions This case underlines the relevance of donor-recipient VRE transmission and invasive infection in the context of intestinal transplantation, highlighting the need for preoperative MDRO screening that facilitates the prompt and effective treatment of possible infections as well as the timely establishment of contact precautions to prevent further spread.

On 7 January 2020, the World Health Organization (WHO) announced a novel coronavirus to be the cause of pneumonia cases whose cause was unclear in China. The infection came to be known as a coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After

MicroRNAs (MiRs) are small, noncoding RNAs that regulate gene expression posttranscriptionally. In this study, we show that MiR-210 is induced by Oct-2, a key transcriptional mediator of B cell activation. Germline deletion of MiR-210 results in the development of autoantibodies from 5 mo of age. Overexpression of MiR-210 in vivo resulted in cell autonomous expansion of the B1 lineage and impaired fitness of B2 cells. Mice overexpressing MiR-210 exhibited impaired class-switched Ab responses, a finding confirmed in wild-type B cells transfected with a MiR-210 mimic. In vitro studies demonstrated defects in cellular proliferation and cell cycle entry, which were consistent with the transcriptomic analysis demonstrating downregulation of genes involved in cellular proliferation and B cell activation. These findings indicate that Oct-2 induction of MiR-210 provides a novel inhibitory mechanism for the control of B cells and autoantibody production.

At mucosal surfaces, the immune system should not initiate inflammatory immune responses to the plethora of antigens constantly present in the environment, but should remain poised to unleash a potent assault on intestinal pathogens. The transcriptional programs and regulatory factors required for immune cells to switch from homeostatic (often tissue-protective) function to potent antimicrobial immunity are poorly defined. Mucosal retinoic-acid-receptor-related orphan receptor-γt-positive (RORγt(+)) innate lymphoid cells (ILCs) are emerging as an important innate lymphocyte population required for immunity to intestinal infections. Various subsets of RORγt(+) ILCs have been described but the transcriptional programs controlling their specification and fate remain largely unknown. Here we provide evidence that the transcription factor T-bet determines the fate of a distinct lineage of CCR6(-)RORγt(+) ILCs. Postnatally emerging CCR6(-)RORγt(+) ILCs upregulated T-bet and this was controlled by cues from the commensal microbiota and interleukin-23 (IL-23). In contrast, CCR6(+)RORγt(+) ILCs, which arise earlier during ontogeny, did not express T-bet. T-bet instructed the expression of T-bet target genes such as interferon-γ (IFN-γ) and of the natural cytotoxicity receptor NKp46. Mice genetically lacking T-bet showed normal development of CCR6(-)RORγt(+) ILCs, but they could not differentiate into NKp46-expressing RORγt(+) ILCs (that is, IL-22-producing natural killer (NK-22) cells) and failed to produce IFN-γ. The production of IFN-γ by T-bet-expressing CCR6(-)RORγt(+) ILCs was essential for the release of mucus-forming glycoproteins required to protect the epithelial barrier during Salmonella enterica infection. Salmonella infection also causes severe enterocolitis that is at least partly driven by IFN-γ. Mice deficient for T-bet or depleted of ILCs developed only mild enterocolitis. Thus, graded expression of T-bet in CCR6(-)RORγt(+) ILCs facilitates the differentiation of IFN-γ-producing CCR6(-)RORγt(+) ILCs required to protect the epithelial barrier against Salmonella infections. Co-expression of T-bet and RORγt, which is also found in subsets of IL-17-producing T-helper (T(H)17) cells, may be an evolutionarily conserved transcriptional program that originally developed as part of the innate defence against infections but that also confers an increased risk of immune-mediated pathology.

Heat shock proteins (HSP) not only function as chaperones for denatured proteins but also for antigenic peptides, thus inducing protective T cell responses. Here we show that vaccination with peptide-loaded HSP70 causes initial interferon-gamma production by murine CD8 T cells but no T cell expansion. These CD8 T cells lacked cytotoxic activity in vitro and in vivo, which was not due to apoptosis. Restimulation with peptide-pulsed dendritic cells both bypassed the proliferative block and suspended the non-protective state of CD8 T lymphocytes in an infection model with the bacterial pathogen, Listeria monocytogenes. Cotransfer of antigen-specific CD4 T cells circumvented the proliferative arrest of CD8 T cells. Our data suggest that HSP vaccines induce CD8 T cell unresponsiveness unless proficient help is provided. Assuming that this model reflects the antigenically experienced human condition where immunological space is restricted and any T cell response possibly leads to suppression of heterologous reactions, our findings bear implications for rational vaccination protocols including those for immunocompromised patients.

Lipids from Mycobacterium tuberculosis are presented through CD1 proteins to T lymphocytes in humans, but the accessory molecules required for antigen loading and presentation remain unidentified. Here we show that fibroblasts deficient in sphingolipid activator proteins (SAPs) transfected with CD1b failed to activate lipid-specific T cells. However, the T cell response was restored when fibroblasts were reconstituted with SAP-C but not other SAPs. Lipid antigen and SAP-C colocalized in lysosomal compartments, and liposome assays showed that SAP-C efficiently extracts antigen from membranes. Coprecipitation demonstrated direct molecular interaction between SAP-C and CD1b. We propose a model in which SAP-C exposes lipid antigens from intralysosomal membranes for loading onto CD1b. Thus, SAP-C represents a missing link in antigen presentation of lipids through CD1b to human T cells.

The epithelium is the main entry point for many viruses, but the processes that protect barrier surfaces against viral infections are incompletely understood. Here we identified interleukin 22 (IL-22) produced by innate lymphoid cell group 3 (ILC3) as an amplifier of signaling via interferon-λ (IFN-λ), a synergism needed to curtail the replication of rotavirus, the leading cause of childhood gastroenteritis. Cooperation between the receptor for IL-22 and the receptor for IFN-λ, both of which were 'preferentially' expressed by intestinal epithelial cells (IECs), was required for optimal activation of the transcription factor STAT1 and expression of interferon-stimulated genes (ISGs). These data suggested that epithelial cells are protected against viral replication by co-option of two evolutionarily related cytokine networks. These data may inform the design of novel immunotherapy for viral infections that are sensitive to interferons.

As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.

Nature Immunology 5, 169–174 (2004). Citation of two papers was accidentally omitted. The paper by Hiraiwa, M., Soeda, S., Kishimoto, Y. & O'Brien, J.S. Binding and transport of gangliosides by prosaposin. Proc. Natl. Acad. Sci. USA 89, 11254–11258 (1992) should have been cited instead of reference 24 on page 171, last paragraph, first sentence.