Papers by Christoph Schoen
Pediatric Infectious Disease Journal, 2020
BACKGROUND Parapneumonic pleural effusion and pleural empyema (PPE/PE) are complications of commu... more BACKGROUND Parapneumonic pleural effusion and pleural empyema (PPE/PE) are complications of community-acquired pneumonia. The objective of this study was to analyze prehospital antibiotic therapy (PH-ABT) of children with PPE/PE and investigate its effects on clinical outcome and pathogen detection. METHODS Prospective nationwide active surveillance in Germany between October 2010 and June 2018. Children and adolescents <18 years of age with pneumonia-associated PE or PPE requiring drainage or with persistence of PPE/PE >7 days were included. RESULTS A total of 1724 children with PPE/PE were reported, of whom 556 children (32.3% of 1719 with available data) received PH-ABT. Children with PH-ABT had a shorter median hospital length of stay (15 vs. 18 days, P < 0.001), a longer time from onset of symptoms until hospital discharge (25 vs. 23 days, P = 0.002), a lower rate of intensive care unit admission (58.3% vs. 64.4%, P = 0.015) and fewer infectious complications (5.9% vs. 10.0%; P = 0.005). Bacterial pathogens in blood or pleural fluid culture were detected in 597 (34.5%) of 1513 children. Positive culture results were less frequent in children with than without PH-ABT (81/466 [17.4%] vs. 299/1005 [29.8%]; P < 0.001), whereas detection rates in pleural fluid samples by polymerase chain reaction were similar (91/181 [50.3%] vs. 220/398 [55.3%]; P = 0.263). CONCLUSIONS In children with PPE/PE, PH-ABT significantly reduced the overall rate of bacterial pathogen detection by culture, but not by polymerase chain reaction. PH-ABT was associated with a lower rate of infectious complications but did not affect the overall duration of disease. We therefore speculate that the duration of PPE/PE is mainly a consequence of an infection-induced inflammatory process, which can only partially be influenced by antibiotic treatment.
JAMA Network Open, 2022
IMPORTANCE Closure of day care centers has been implemented globally to contain the COVID-19 pand... more IMPORTANCE Closure of day care centers has been implemented globally to contain the COVID-19 pandemic but has negative effects on children's health and psychosocial well-being. OBJECTIVE To investigate the feasibility of surveillance among children and childcare workers and to model the efficacy of surveillance on viral spread prevention. DESIGN, SETTING, AND PARTICIPANTS This nonrandomized controlled trial was conducted at 9 day care centers in Wuerzburg, Germany, from October 2020 to March 2021. Participants included children attending day care, childcare workers, and household members. Participating day care centers were assigned to different surveillance modules in a nonrandomized feasibility study. A mathematical model for SARS-CoV-2 spread in day care centers was developed to identify optimal surveillance. INTERVENTIONS Modules 1, 2, and 3 involved continuous surveillance of asymptomatic children and childcare workers by SARS-CoV-2 polymerase chain reaction testing of either midturbinate nasal swabs twice weekly (module 1) or once weekly (module 2) or self-sampled saliva samples twice weekly (module 3). Module 4 involved symptom-based, on-demand testing of children, childcare workers, and their household members by oropharyngeal swabs. All participants underwent SARS-CoV-2 antibody status testing before and after the sampling period. Questionnaires on attitudes and perception of the pandemic were administered in weeks 1, 6, and 12. Mathematical modeling was used to estimate SARS-CoV-2 spread in day care centers. MAIN OUTCOMES AND MEASURES The primary outcomes were acceptance of the respective surveillance protocols (feasibility study) and the estimated number of secondary infections (mathematical modeling). RESULTS Of 954 eligible individuals (772 children and 182 childcare workers), 592 (62%), including 442 children (median [IQR] age, 3 [2-4] years; 214 [48.6%] female) and 150 childcare workers (median [IQR] age, 29 [25-44] years; 129 [90.8%] female) participated in the surveillance. In total, 4755 tests for SARS-CoV-2 detected 2 infections (1 childcare worker and 1 adult household member). Acceptance for continuous surveillance was highest for biweekly saliva testing (150 of 221 eligible individuals [67.9%; 95% CI, 61.5%-73.7%]) compared with biweekly (51 of 117 individuals [43.6%; 95% CI, 35.0%-52.6%]) and weekly (44 of 128 individuals [34.4%; 95% CI, 26.7%-43.0%]) midturbinate swabbing (P < .001). Dropout rates were higher for midturbinate swabbing (biweekly, 11 of 62 participants [18%]; once weekly, 11 of 55 participants [20%]) than for saliva testing (6 of 156 (continued) Key Points Question Is continuous SARS-CoV-2 testing accepted by children, parents, and childcare workers and can it prevent viral spreading in day care centers? Findings In this nonrandomized controlled trial, surveillance testing for SARS-CoV-2 among 954 eligible individuals was well accepted by children, parents, and childcare workers if saliva sampling at home was used. Mathematical modeling based on study and literature data identified biweekly testing of at least 50% of children and childcare workers as minimal requirements to limit secondary infections. Meaning These findings suggest that SARS-CoV-2 surveillance testing is feasible and allows for continued day care attendance for children during the COVID-19 pandemic.
Science, 2021
Cellular RNAs guide CRISPR-Cas9 The Cas9 nuclease widely used for genome editing is derived from ... more Cellular RNAs guide CRISPR-Cas9 The Cas9 nuclease widely used for genome editing is derived from natural bacterial defense systems that protect against invading viruses. Cas9 is directed by RNA guides to cut matching viral DNA. Jiao et al. discovered that RNA guides can also originate from cellular RNAs unassociated with viral defense (see the Perspective by Abudayyeh and Gootenberg). They rendered this process programmable, linking the presence of virtually any RNA to cutting of matching DNA by Cas9. This capability is the basis of a new CRISPR diagnostic method developed by the authors that can detect many biomarkers at once. Named LEOPARD, this method can detect, for example, RNAs from severe acute respiratory syndrome coronavirus 2 and other viruses, thereby translating a new CRISPR discovery into a powerful diagnostic tool. Science , abe7106, this issue p. 941 ; see also abi9335, p. 914
Scientific Reports, 2017
Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant a... more Tuberculosis (TB) and the spread of Mycobacterium tuberculosis complex (MTBC) strains resistant against rifampin (RIF) and isoniazid (INH) pose a serious threat to global health. However, rapid and reliable MTBC detection along with RIF/INH susceptibility testing are challenging in low prevalence countries due to the higher rate of false positives. Here, we provide the first performance data for the artus MTBC PCR assay in a low prevalence setting. We analyze 1323 respiratory and 311 non-respiratory samples with the artus MTBC PCR assay as well as by mycobacterial culture and microscopy. We propose retesting of specimens in duplicate and consideration of a determined cycle-threshold value cutoff greater than 34, as this significantly increases accuracy, specificity, and negative predictive value without affecting sensitivity. Furthermore, we tested fourteen MTBC positive samples with the GenoType MTBDRplus test and demonstrate that using an identical DNA extraction protocol for both assays does not impair downstream genotypic testing for RIF and INH susceptibility. In conclusion, our procedure optimizes the use of the artus MTB assay with workload efficient methods in a low incidence setting. Combining the modified artus MTB with the GenoType MTBDRplus assays allows rapid and accurate detection of MTBC and RIF/INH resistance.
JMM Case Reports, 2017
Introduction. Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal a... more Introduction. Tropheryma whipplei is the causative agent of Whipple's disease. Gastrointestinal and lymphatic tissues are affected in the majority of cases, resulting in diarrhoea, malabsorption and fever. Here, we report a rare case of ocular manifestation in a patient lacking the typical Whipple symptoms. Case presentation. A 74-year-old Caucasian female presented with blurred vision in the right eye over a period of 1-2 months, accompanied by stinging pain and conjunctival hyperaemia for the last 2 days. Upon admission, visual acuity was hand motion in the affected eye. Ophthalmological examination showed typical signs of intraocular inflammation. Diagnostic and therapeutic pars plana vitrectomy including vitreous biopsy and intravitreal instillation of vancomycin and amikacin was performed within hours of initial presentation. Both microscopic analysis and microbial cultures of the vitreous biopsy remained negative for bacteria and fungi. The postoperative antibiotic regime included intravenous administration of ceftriaxone in combination with topical tobramycin and ofloxacin. Due to the empirical therapy the inflammation ceased and the patient was discharged after 5 days with cefpodoxime orally and local antibiotic and steroidal therapy. Meanwhile, the vitreous body had undergone testing by PCR for the eubacterial 16S rRNA gene, which was found to be positive. Analysis of the PCR product revealed a specific sequence of T. whipplei. Conclusion. In our patient, endophthalmitis was the first and only symptom of Morbus Whipple, while most patients with Whipple's disease suffer from severe gastrointestinal symptoms. 16S rDNA PCR should be considered for any intraocular infection when microscopy and standard culture methods remain negative.
Nucleic acids research, Jan 17, 2017
Neisseria meningitidis is a human commensal that can also cause life-threatening meningitis and s... more Neisseria meningitidis is a human commensal that can also cause life-threatening meningitis and septicemia. Despite growing evidence for RNA-based regulation in meningococci, their transcriptome structure and output of regulatory small RNAs (sRNAs) are incompletely understood. Using dRNA-seq, we have mapped at single-nucleotide resolution the primary transcriptome of N. meningitidis strain 8013. Annotation of 1625 transcriptional start sites defines transcription units for most protein-coding genes but also reveals a paucity of classical σ70-type promoters, suggesting the existence of activators that compensate for the lack of -35 consensus sequences in N. meningitidis. The transcriptome maps also reveal 65 candidate sRNAs, a third of which were validated by northern blot analysis. Immunoprecipitation with the RNA chaperone Hfq drafts an unexpectedly large post-transcriptional regulatory network in this organism, comprising 23 sRNAs and hundreds of potential mRNA targets. Based on t...
PloS one, 2017
Some members of the physiological human microbiome occasionally cause life-threatening disease ev... more Some members of the physiological human microbiome occasionally cause life-threatening disease even in immunocompetent individuals. A prime example of such a commensal pathogen is Neisseria meningitidis, which normally resides in the human nasopharynx but is also a leading cause of sepsis and epidemic meningitis. Using N. meningitidis as model organism, we tested the hypothesis that virulence of commensal pathogens is a consequence of within host evolution and selection of invasive variants due to mutations at contingency genes, a mechanism called phase variation. In line with the hypothesis that phase variation evolved as an adaptation to colonize diverse hosts, computational comparisons of all 27 to date completely sequenced and annotated meningococcal genomes retrieved from public databases showed that contingency genes are indeed enriched for genes involved in host interactions. To assess within-host genetic changes in meningococci, we further used ultra-deep whole-genome sequen...
Pediatric pulmonology, Jan 20, 2016
To evaluate the initial management of pediatric parapneumonic effusion or pleural empyema (PPE/PE... more To evaluate the initial management of pediatric parapneumonic effusion or pleural empyema (PPE/PE) with regard to length of hospital stay (LOS). Collection of pediatric PPE/PE cases using a nationwide surveillance system (ESPED) from 10/2010 to 06/2013, in all German pediatric hospitals. Inclusion of PPE/PE patients <18 years of age requiring drainage or with a PPE/PE persistence >7 days. Staging of PPE/PE based on reported pleural sonographic imaging. Comparison of LOS after diagnosis between children treated with different forms of initial invasive procedures performed ≤3 days after PPE/PE diagnosis: pleural puncture, draining catheter, intrapleural fibrinolytic therapy, surgical procedures. Inclusion of 645 children (median age 5 years); median total LOS 17 days. Initial therapy was non-invasive in 282 (45%) cases and invasive in 347 (55%) cases (pleural puncture: 62 [10%], draining catheter: 153 [24%], intrapleural fibrinolytic therapy: 89 [14%], surgical procedures: 43 [7...
Emerging Infectious Diseases, 2015
, caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. olig... more , caused by polycystic larvae of the tapeworm Echinococcus vogeli and unicystic larvae of E. oligarthrus, is an emerging infection in rural South America (1,2). The parasites are propagated in a predator-prey cycle; the final and intermediate hosts for E. vogeli are bush dogs (Speothos venaticus) and pacas (Cuniculus paca), respectively (1,2). Human infections occur in rural areas and have been reported from several South American countries, mostly Brazil (1-3). Prompted by the recent diagnosis of an E. vogeli infection in a Surinamese patient in the Netherlands (4), we performed a retrospective analysis of all recent echinococcosis cases seen at the Amsterdam Medical Center. We describe molecular and immunohistochemical analyses from another case of E. vogeli infection. In 2009, a 48-year-old female schoolteacher from Suriname sought care at the Amsterdam Medical Center for recently increasing retrosternal pain. Born in rural Suriname, she moved to the capital city of Paramaribo at 2 years of age. She had worked in the Brokopondo District for 1 year, then worked in urban Morocco, and immigrated to the Netherlands in 1990. Physical and laboratory examination findings were unremarkable. Esophago-gastro-duodenoscopy showed no abnormality. Abdominal ultrasonography and subsequent computed tomography revealed a lesion with solid and liquid components in liver segment 4, considered consistent with a biliary cystadenoma or an echinococcal cyst. Result of an echinococcosis indirect hemagglutination test with E. granulosus hydatid fluid antigen (Fumouze, Levallois-Perret, France) was strongly positive
Robinson/Population Genetics of Bacteria, 2010
... al., 2004 ; Urwin et al., 2004 ), FetA (Thompson et al., 2003 ; Bennett et al., 2009 ), Opa (... more ... al., 2004 ; Urwin et al., 2004 ), FetA (Thompson et al., 2003 ; Bennett et al., 2009 ), Opa (Callaghan et al., 2008 ), PenA (Taha et al ... Germany, which were obtained by the Bavarian meningococcal carriage study (Claus et al., 2005 ) and for strains from invasive diseases (Elias et al ...
Genome Plasticity and Infectious Diseases
This chapter on mechanisms of genome plasticity in Neisseria meningitidis initially gives a short... more This chapter on mechanisms of genome plasticity in Neisseria meningitidis initially gives a short overview over the genetic variability at the population level and some peculiarities of meningococcal genome organization as revealed by genome sequencing projects. Later, the focus is on genetic mechanisms and genomic features that are paramount for the generation of genomic flexibility, and a brief account of the genetic basis of virulence in Neisseria meningitidis as far as it is known today. Exogenous and endogenous stress induces DNA damage in the meningococcal genome that must be repaired, and DNA repair mechanisms are therefore likely to have a key role in meningococcal genome dynamics. So far, Escherichia coli has served as the prime model organism for DNA repair systems in other microorganisms such as N. meningitidis. The majority of strong mutators found in a number of bacterial species have a defective MMR pathway due to the inactivation of mutS or mutL genes. In addition to global mutation and phase variation, intragenomic as well as intergenomic recombination is of pivotal importance for the generation of genome flexibility in N. meningitidis, and one of the most striking characteristics of the meningococcal genomes is the abundance and diversity of repetitive DNA serving as potential target sites for homologous recombination or replication slippage.
Methods in Molecular Biology, 2011
Infectious disease research has been revolutionized by two recent developments in the field of ge... more Infectious disease research has been revolutionized by two recent developments in the field of genome biology: (1) the sequencing of the human genome as well as many pathogen genomes and (2) the development of high-throughput technologies including microarray technology, proteomics, and metabolomics. Microarray studies enable a deeper understanding of the genetic evolution of pathogens and investigation of the determinants of pathogenicity on a whole-genome scale. Host studies, in turn, allow for an unprecedented holistic appreciation of the complexities of host cell responses at the molecular level. In combination, host-pathogen studies allow global analysis of gene expression in the infecting bacterium as well as in the infected host cell during pathogenesis, providing a comprehensive picture of the intricacies of pathogen-host interactions. In this chapter, we briefly explain the principles underlying DNA microarrays including the major points to consider when planning and analyzing microarray experiments and we describe in detail their practical application, using the interaction of Neisseria meningitidis with human endothelial or epithelial cells as examples.
PLoS ONE, 2011
Background: Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing ... more Background: Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH) and multilocus sequence typing (MLST) of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences.
Nucleic Acids Research, 2009
Multiple sequence alignments (MSAs) are one of the most important sources of information in seque... more Multiple sequence alignments (MSAs) are one of the most important sources of information in sequence analysis. Many methods have been proposed to detect, extract and visualize their most significant properties. To the same extent that site-specific methods like sequence logos successfully visualize site conservations and sequencebased methods like clustering approaches detect relationships between sequences, both types of methods fail at revealing informational elements of MSAs at the level of sequence-site interactions, i.e. finding clusters of sequences and sites responsible for their clustering, which together account for a high fraction of the overall information of the MSA. To fill this gap, we present here a method that combines the Fisher score-based embedding of sequences from a profile hidden Markov model (pHMM) with correspondence analysis. This method is capable of detecting and visualizing group-specific or conflicting signals in an MSA and allows for a detailed explorative investigation of alignments of any size tractable by pHMMs. Applications of our methods are exemplified on an alignment of the Neisseria surface antigen LP2086, where it is used to detect sites of recombinatory horizontal gene transfer and on the vitamin K epoxide reductase family to distinguish between evolutionary and functional signals.
Molecular Cell, 2013
CRISPR interference confers adaptive, sequencebased immunity against viruses and plasmids and is ... more CRISPR interference confers adaptive, sequencebased immunity against viruses and plasmids and is specified by CRISPR RNAs (crRNAs) that are transcribed and processed from spacer-repeat units. Pre-crRNA processing is essential for CRISPR interference in all systems studied thus far. Here, our studies of crRNA biogenesis and CRISPR interference in naturally competent Neisseria spp. reveal a unique crRNA maturation pathway in which crRNAs are transcribed from promoters that are embedded within each repeat, yielding crRNA 5 0 ends formed by transcription and not by processing. Although crRNA 3 0 end formation involves RNase III and trans-encoded tracrRNA, as in other type II CRISPR systems, this processing is dispensable for interference. The meningococcal pathway is the most streamlined CRISPR/Cas system characterized to date. Endogenous CRISPR spacers limit natural transformation, which is the primary source of genetic variation that contributes to immune evasion, antibiotic resistance, and virulence in the human pathogen N. meningitidis.
Journal of Clinical Microbiology, 2009
Daptomycin is a novel lipopeptide antibiotic agent approved for the treatment of gram-positive li... more Daptomycin is a novel lipopeptide antibiotic agent approved for the treatment of gram-positive life-threatening infections. Here we report, for the first time, the isolation of a highly daptomycin-resistant strain of Corynebacterium jeikeium causing a life-threatening infection in a neutropenic patient undergoing cord blood transplantation for secondary acute myeloid leukemia.
Journal of Clinical Microbiology, 2012
R ecently, Geosentinel has been notified of patients with acute muscular Sarcocystis-like infecti... more R ecently, Geosentinel has been notified of patients with acute muscular Sarcocystis-like infections related to travel to Tioman Island, peninsular Malaysia (1). The outbreak started in the summer of 2011, and the initial patients were seen in Würzburg, Germany (2). The epidemic is currently ongoing, with a second wave of diseased travelers returning since the summer of 2012 (1). The organism responsible has not yet been properly characterized, but the clinical symptoms, laboratory parameters, and the histopathological characteristics shown in this report are highly compatible with a zoonotic Sarcocystis infection. Here we describe the initial cluster of patients and a muscle biopsy specimen showing this Sarcocystis-like infective agent for the first time. In the period from 21 to 27 September 2011, 5 patients (3 males and 2 females; aged 31 to 32 years) were referred to the Department of Tropical Medicine, Medical Mission Hospital, Würzburg, Germany, with persisting severe myalgia after travel (Table 1). All had spent their vacation from 10 to 30 July 2011, in peninsular Malaysia with a stay on Tioman Island (July 20 to 29), 32 km off the east coast in the South China Sea (2°48= 47Љ N, 104°11= 17Љ E). A few days after returning home, all travelers, who belonged to a tourist group from southern Germany, had started suffering from a flu-like illness. Symptoms had commenced between August 1 and 8 with fatigue, headache, fever of 38 or 39°C, arthralgia (mild to moderate), and muscle pain (moderate to very severe) in the back and extremities. One patient suffered from watery diarrhea and urticarial rash 1 day before the onset of fever and later developed tachycardia, palpitations, and a recurring rash. Two patients reported that the pain had moved from the arms to the legs and then to the back from day to day, and one of these two patients had also developed a rash and cough. The pain was either increasing or persisting and located in the thighs, calves, upper arms, back, and in one patient also in the tongue. Electrocardiograms were unremarkable, except for one patient, who had an incomplete right bundle branch block and few ventricular extrasystoles. In all trav
Journal of Clinical Microbiology, 2012
Spondylodiscitis caused by Campylobacter species is a rare disease which is most often caused by ... more Spondylodiscitis caused by Campylobacter species is a rare disease which is most often caused by Campylobacter fetus . We report a case of culture-negative spondylodiscitis and a psoas abscess due to Campylobacter jejuni in a 68-year-old woman, as revealed by 16S rRNA gene and Campylobacter -specific PCRs from biopsied tissue.
Journal of Bacteriology, 2010
Neisseria meningitidis serogroup B strains are responsible for most meningococcal cases in the in... more Neisseria meningitidis serogroup B strains are responsible for most meningococcal cases in the industrialized countries, and strains belonging to the clonal complex ST-41/44 are among the most prevalent serogroup B strains in carriage and disease. Here, we report the first genome and transcriptome comparison of a serogroup B carriage strain from the clonal complex ST-41/44 to the serogroup B disease strain MC58 from the clonal complex ST-32. Both genomes are highly colinear, with only three major genome rearrangements that are associated with the integration of mobile genetic elements. They further differ in about 10% of their gene content, with the highest variability in gene presence as well as gene sequence found for proteins involved in host cell interactions, including Opc, NadA, TonB-dependent receptors, RTX toxin, and two-partner secretion system proteins. Whereas housekeeping genes coding for metabolic functions were highly conserved, there were considerable differences in t...
Journal of Bacteriology, 2005
Listeria monocytogenes mutants with deletions in aroA , aroB , or aroE exhibited strong posttrans... more Listeria monocytogenes mutants with deletions in aroA , aroB , or aroE exhibited strong posttranscriptional upregulation of internalin A (InlA) and InlB synthesis, which resulted in a more-than-10-fold increase in InlA-mediated internalization by epithelial Caco-2 cells and a 4-fold increase in InlB-mediated internalization by microvascular endothelial cells (human brain microvascular endothelial cells) compared to the wild-type strain. The increase in InlA and InlB production was not due to enhanced PrfA- and/or sigma factor B (SigB)-dependent inlAB transcription but was caused by enhanced translation of the inlAB transcripts in the aro mutants. All inlA ( B ) transcripts had a 396-nucleotide upstream 5′ untranslated region (UTR). Different deletions introduced into this UTR led to significant reductions in InlA and InlB synthesis; enhanced translation of all of the truncated transcripts in the aro mutants was, however, still observed. Thus, translation of the inlAB transcripts was...
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Papers by Christoph Schoen