Diphtheria in a Swiss Asylum Seeker Reception Centre: Outbreak Investigation and Evaluation of Testing and Vaccination Strategies.

Objectives: To describe a suspected diphtheria outbreak in a Swiss asylum seeker reception centre, and to analyse its management response regarding testing and vaccination. Methods: We retrospectively analysed clinical, microbiology, and case management data of all asylum seekers tested for C. diphtheriae between 28th August and 31st December 2022 while residing at the centre. Results are reported descriptively. Results: Among 265 individuals tested, ten cases of cutaneous diphtheria, one simultaneous respiratory and cutaneous case, and nine respiratory carriers were identified. Mass throat screening, targeted throat testing and targeted wound testing yielded 4.8%, 4.3%, and 17.4% positive results, respectively. No respiratory carrier was identified among cutaneous cases undergoing a throat swab, and no symptomatic case was identified among individuals with unspecific throat symptoms. Rates of vaccination implementation of newly arriving asylum seekers before and after the outbreak were low (17.5% and 15.5%, respectively), as were rates of targeted vaccination among cases and close contacts. Conclusion: We provide evidence for transmission both prior to arrival and within the setting, suboptimal practices and timeliness of testing, and implementation gaps in vaccination.

Potential value of a rapid syndromic multiplex PCR for the diagnosis of native and prosthetic joint infections: a real-world evidence study.

Introduction: The BIOFIRE Joint Infection (JI) Panel is a diagnostic tool that uses multiplex-PCR testing to detect microorganisms in synovial fluid specimens from patients suspected of having septic arthritis (SA) on native joints or prosthetic joint infections (PJIs). Methods: A study was conducted across 34 clinical sites in 19 European and Middle Eastern countries from March 2021 to June 2022 to assess the effectiveness of the BIOFIRE JI Panel. Results: A total of 1527 samples were collected from patients suspected of SA or PJI, with an overall agreement of 88.4 % and 85 % respectively between the JI Panel and synovial fluid cultures (SFCs). The JI Panel detected more positive samples and microorganisms than SFC, with a notable difference on Staphylococcus aureus, Streptococcus species, Enterococcus faecalis, Kingella kingae, Neisseria gonorrhoeae, and anaerobic bacteria. The study found that the BIOFIRE JI Panel has a high utility in the real-world clinical setting for suspected SA and PJI, providing diagnostic results in approximately 1 h. The user experience was positive, implying a potential benefit of rapidity of results' turnover in optimising patient management strategies. Conclusion: The study suggests that the BIOFIRE JI Panel could potentially optimise patient management and antimicrobial therapy, thus highlighting its importance in the clinical setting.

Novel Organism Verification and Analysis (NOVA) study: identification of 35 clinical isolates representing potentially novel bacterial taxa using a pipeline based on whole genome sequencing.

BACKGROUND: Reliable species identification of cultured isolates is essential in clinical bacteriology. We established a new study algorithm named NOVA - Novel Organism Verification and Analysis to systematically analyze bacterial isolates that cannot be characterized by conventional identification procedures MALDI-TOF MS and partial 16 S rRNA gene sequencing using Whole Genome Sequencing (WGS). RESULTS: We identified a total of 35 bacterial strains that represent potentially novel species. Corynebacterium sp. (n = 6) and Schaalia sp. (n = 5) were the predominant genera. Two strains each were identified within the genera Anaerococcus, Clostridium, Desulfovibrio, and Peptoniphilus, and one new species was detected within Citrobacter, Dermabacter, Helcococcus, Lancefieldella, Neisseria, Ochrobactrum (Brucella), Paenibacillus, Pantoea, Porphyromonas, Pseudoclavibacter, Pseudomonas, Psychrobacter, Pusillimonas, Rothia, Sneathia, and Tessaracoccus. Twenty-seven of 35 strains were isolated from deep tissue specimens or blood cultures. Seven out of 35 isolated strains identified were clinically relevant. In addition, 26 bacterial strains that could only be identified at the species level using WGS analysis, were mainly organisms that have been identified/classified very recently. CONCLUSION: Our new algorithm proved to be a powerful tool for detection and identification of novel bacterial organisms. Publicly available clinical and genomic data may help to better understand their clinical and ecological role. Our identification of 35 novel strains, 7 of which appear to be clinically relevant, shows the wide range of undescribed pathogens yet to define.

Evaluation of the clinical relevance of the Biofire© FilmArray pneumonia panel among hospitalized patients.

PURPOSE: Panel PCR tests provide rapid pathogen identification. However, their diagnostic performance is unclear. We assessed the performance of the Biofire© FilmArray pneumonia (PN)-panel against standard culture in broncho-alveolar lavage (BAL) samples. METHODS: Setting: University Hospital Basel (February 2019 to July 2020), including hospitalized patients with a BAL (± pneumonia). We determined sensitivity and specificity of the PN-panel against standard culture. Using univariate logistic regression, we calculated odds ratios (OR) for pneumonia according to PN-panel and culture status, stratifying by chronic pulmonary disease. We calculated ORs for pneumonia for different pathogens to estimate the clinical relevance. RESULTS: We included 840 adult patients, 60% were males, median age was 68 years, 35% had chronic pulmonary disease, 21% had pneumonia, and 36% had recent antibiotic use. In 1078 BAL samples, bacterial pathogens were detected in 36% and 16% with PN-panel and culture, respectively. The overall sensitivity and specificity of the PN-panel was high, whereas the positive predictive value was low. The OR of pneumonia was 1.1 (95% CI 0.7-1.6) for PN-panel-positive only; 2.6 (95% CI 1.3-5.3) for culture-positive only, and 1.6 (95% CI 1.0-2.4) for PN-panel and culture-positive. The detection rate of Haemophilus influenzae, Staphylococcus aureus, and Moraxella catarrhalis in the PN-panel was high but not associated with pneumonia. CONCLUSION: While sensitivity and specificity of PN-panel are high compared to culture, pathogen detection did not correlate well with a pneumonia diagnosis. Patients with culture-positive BAL had the highest OR for pneumonia-thus the impact of the PN-panel on clinical management needs further evaluation in randomized controlled trials.

Cefepime versus carbapenems for treatment of AmpC beta-lactamase-producing Enterobacterales bloodstream infections.

PURPOSE: Cefepime is recommended for treating infections caused by AmpC beta-lactamase-producing Enterobacterales (AmpC-PE), though supporting evidence is limited. Therefore, this study compared outcomes associated with cefepime versus carbapenem therapy for bloodstream infections (BSIs) caused by AmpC-PE after phenotypic exclusion of ESBL-co-producing isolates. METHODS: This retrospective cohort study compared definite cefepime versus carbapenem treatment for AmpC-PE BSI in hospitalized patients of the University Hospital Basel, Switzerland, between 01/2015 and 07/2020. Primary outcomes included in-hospital death, renal impairment and neurologic adverse events; secondary outcomes included length of hospital stay and recurrent infection. RESULTS: Two hundred and seventy episodes of AmpC-PE BSI were included, 162, 77 and 31 were treated with a carbapenem, cefepime and other antibiotics, respectively. Patients treated with carbapenems were more likely to be transferred to the ICU on admission and more frequently had central venous catheter as a source of infection. In uni- and multivariable analyses, primary and secondary outcomes did not differ between the two treatment groups, except for more frequent occurrence of neurological adverse events among patients treated with carbapenems and shorter length of hospital stay among survivors treated with cefepime. CONCLUSION: After excluding isolates with phenotypic ESBL-co-production, cefepime was not associated with adverse outcomes compared to carbapenems when used to treat BSIs caused by AmpC-PE. Our study provides evidence to support the use of cefepime as a safe treatment strategy for AmpC-PE BSI, particularly in clinically stable patients without initial renal impairment or increased susceptibility to neurological adverse events.

Epidemiology of patients harboring carbapenemase-producing bacteria and comparison with patients with detection of extended-spectrum beta-lactamase-producing Enterobacterales-A retrospective cohort study.

OBJECTIVE: We evaluated the epidemiology of carbapenemase-producing bacteria (CPB) in Switzerland by comparing risk factors between patients colonized with CPB and patients colonized with extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PE). METHODS: This retrospective cohort study was conducted at the University Hospital Basel in Switzerland. Hospitalized patients with CPB in any sample between January 2008 and July 2019 were included. The ESBL-PE group consisted of hospitalized patients with detection of ESBL-PE from any sample between January 2016 and December 2018. Comparisons of risk factors for acquisition of CPB and ESBL-PE were performed by logistic regression. RESULTS: Inclusion criteria were met for 50 patients in the CPB group and 572 in the ESBL-PE group. In the CPB group, 62% had a travel history and 60% had been hospitalized abroad. When comparing the CPB group to the ESBL-PE group, hospitalization abroad (odds ratio [OR], 25.33; 95% confidence interval [CI], 11.07-57.98) and prior antibiotic therapy (OR, 4.76; 95% CI, 2.15-10.55) remained independently associated with CPB colonization. Hospitalization abroad (P < .001) and prior antibiotic therapy (P < .001) predicted CPB in the comparison of CPB with ESBL Escherichia coli, whereas hospitalization abroad was associated with CPB in comparison to ESBL Klebsiella pneumoniae. CONCLUSIONS: Although CPB still seem to be mainly imported from areas of higher endemicity, local acquisition of CPB is emerging, especially in patients with close and/or frequent contact with healthcare services. This trend resembles the epidemiology of ESBL K. pneumoniae, supporting mainly healthcare-associated transmission. Frequent evaluation of CPB epidemiology is required to improve detection of patients at risk of CPB carriage.

Diagnostic challenges within the Bacillus cereus-group: finding the beast without teeth.

The Bacillus cereus-group (B. cereus sensu lato) includes common, usually avirulent species, often considered contaminants of patient samples in routine microbiological diagnostics, as well as the highly virulent B. anthracis. Here we describe 16 isolates from 15 patients, identified as B. cereus-group using a MALDI-TOF MS standard database. Whole genome sequencing (WGS) analysis identified five of the isolates as B. anthracis species not carrying the typical virulence plasmids pXO1 and pXO2, four isolates as B. paranthracis, three as B. cereus sensu stricto, two as B. thuringiensis, one as B. mobilis, and one isolate represents a previously undefined species of Bacillus (B. basilensis sp. nov.). More detailed analysis using alternative MALDI-TOF MS databases, biochemical phenotyping, and diagnostic PCRs, gave further conflicting species results. These cases highlight the difficulties in identifying avirulent B. anthracis within the B. cereus-group using standard methods. WGS and alternative MALDI-TOF MS databases offer more accurate species identification, but so far are not routinely applied. We discuss the diagnostic resolution and discrepancies of various identification methods.

Patients exposed to vancomycin-resistant enterococci during in-hospital outbreaks in a low endemic setting: a proposal for risk-based screening.

BACKGROUND: The optimal extent of screening of contact patients (CoPat) after exposure to patients infected or colonized with vancomycin-resistant enterococci (VRE) remains controversial. METHODS: We retrospectively developed a new risk stratification for screening patients exposed to VRE, based on data from three outbreaks-two with Enterococcus faecium vanB and one with Enterococcus faecium vanA involving 1096 CoPat-in a low endemic setting. We classified them into four risk groups: three on environmental exposure, one by healthcare exposure: high (sharing the same room/bathroom with a VRE-colonized patient), medium (hospitalization in the same room after a VRE-colonized patient's discharge until terminal disinfection including ultraviolet C (UVc)-disinfection), low (hospitalized in the same room within three weeks before the VRE-colonized patient), and "staff" (screening of patients having the same medical care team). RESULTS: VRE-transmission occurred in 7.9% in the high-risk group compared to 0.6% and 0% in the medium and low risk groups. There was a significant trend to higher rates of transmission by risk level of exposure (p < 0.001). In the "staff" group, VRE transmission rate was 2.3%. CONCLUSION: Based on this stratification, we recommend to focus screening of exposed CoPat on the high-risk and "staff" group, saving resources and costs, but larger studies will allow to further improve the yield of VRE screening in the outbreak setting.

Distribution of Aspergillus Species and Prevalence of Azole Resistance in Respiratory Samples From Swiss Tertiary Care Hospitals.

Among 400 Aspergillus species from respiratory samples in Switzerland, Aspergillus fumigatus was the most frequent species. Non-fumigatus Aspergillus spp were more prevalent among solid organ transplant recipients and after azole exposure. Azole resistance was detected in 4 A fumigatus isolates, 3 of them with the "environmental" mutation TR34/L98H in the cyp51A gene.

Description of Pseudoclavibacter triregionum sp. nov. from human blood and Pseudoclavibacter albus comb. nov., and revised classification of the genus Pseudoclavibacter: proposal of Caespitibacter gen. nov., with Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov.

We present polyphasic taxonomic data to demonstrate that strain 125703-2019T, a human blood isolate, represents a novel species within the genus Pseudoclavibacter, and to reclassify the illegitimate Zimmermannella alba Lin et al., 2004 as Pseudoclavibacter albus comb. nov. Upon primary isolation, strain 125703-2019T could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that it belonged to the genus Pseudoclavibacter. Average nucleotide identity and digital DNA-DNA hybridisation analyses confirmed that it represented a novel species within this genus. A detailed physiological characterisation yielded differential tests between the novel species and its nearest neighbor taxa, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify this strain into the novel species Pseudoclavibacter triregionum sp. nov., with strain 125703-2019T (= R-76471T, LMG 31777T, CCUG 74796T) as the type strain. The whole-genome assembly of strain 125703-2019T has a size of 2.4 Mb and a G + C content of 72.74%. A Pseudoclavibacter pangenome analysis revealed that 667 gene clusters were exclusively present in strain 125703-2019T. While these gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that explained the occurrence of this species in human infection. Finally, several phylogenetic and phylogenomic analyses demonstrated that the genus Pseudoclavibacter is polyphyletic with Pseudoclavibacter soli and Pseudoclavibacter caeni representing a unique and deeply branching line of descent within the family Microbacteriaceae. We therefore also propose to reclassify both species into the novel genus Caespitibacter gen. nov. as Caespitibacter soli comb. nov. and Caespitibacter caeni comb. nov., respectively, and with C. soli comb. nov. as the type species.

Trends of the Epidemiology of Candidemia in Switzerland: A 15-Year FUNGINOS Survey.

BACKGROUND: The increasing incidence of candidemia and emergence of drug-resistant Candida species are major concerns worldwide. Long-term surveillance studies are needed. METHODS: The Fungal Infection Network of Switzerland (FUNGINOS) conducted a 15-year (2004-2018), nationwide, epidemiological study of candidemia. Hospital-based incidence of candidemia, Candida species distribution, antifungal susceptibility, and consumption were stratified in 3 periods (2004-2008, 2009-2013, 2014-2018). Population-based incidence over the period 2009-2018 derived from the Swiss Antibiotic Resistance Surveillance System (ANRESIS). RESULTS: A total of 2273 Candida blood isolates were studied. Population and hospital-based annual incidence of candidemia increased from 2.96 to 4.20/100 000 inhabitants (P = .022) and 0.86 to 0.99/10 000 patient-days (P = .124), respectively. The proportion of Candida albicans decreased significantly from 60% to 53% (P = .0023), whereas Candida glabrata increased from 18% to 27% (P < .0001). Other non-albicans Candida species remained stable. Candida glabrata bloodstream infections occurred predominantly in the age group 18-40 and above 65 years. A higher proportional increase of C glabrata was recorded in wards (18% to 29%, P < .0001) versus intensive care units (19% to 24%, P = .22). According to Clinical and Laboratory Standards Institute, nonsusceptibility to fluconazole in C albicans was observed in 1% of isolates, and anidulafungin and micafungin nonsusceptibility was observed in 2% of C albicans and C glabrata. Fluconazole consumption, the most frequently used antifungal, remained stable, whereas use of mold-active triazoles and echinocandins increased significantly in the last decade (P < .0001). CONCLUSIONS: Over the 15-year period, the incidence of candidemia increased. A species shift toward C glabrata was recently observed, concurring with increased consumption of mold-active triazoles.

Gulosibacter hominis sp. nov.: a novel human microbiome bacterium that may cause opportunistic infections.

We present genomic, phylogenomic, and phenotypic taxonomic data to demonstrate that three human ear isolates represent a novel species within the genus Gulosibacter. These isolates could not be identified reliably using MALDI-TOF mass spectrometry during routine diagnostic work, but partial 16S rRNA gene sequence analysis revealed that they belonged to the genus Gulosibacter. Overall genomic relatedness indices between the draft genome sequences of the three isolates and of the type strains of established Gulosibacter species confirmed that the three isolates represented a single novel Gulosibacter species. A biochemical characterisation yielded differential tests between the novel and established Gulosibacter species, which could also be differentiated using MALDI-TOF mass spectrometry. We propose to formally classify these three isolates into Gulosibacter hominis sp. nov., with 401352-2018 T (= LMG 31778 T, CCUG 74795 T) as the type strain. The whole-genome sequence of strain 401352-2018 T has a size of 2,340,181 bp and a G+C content of 62.04 mol%. A Gulosibacter pangenome analysis revealed 467 gene clusters that were exclusively present in G. hominis genomes. While these G. hominis specific gene clusters were enriched in several COG functional categories, this analysis did not reveal functions that suggested a role in the human microbiome, nor did it explain the occurrence of G. hominis in ear infections. The absence of acquired antimicrobial resistance determinants and virulence factors in the G. hominis genomes, and an analysis of publicly available 16S rRNA gene sequences and 16S rRNA amplicon sequencing data sets suggested that G. hominis is a member of the human skin microbiota that may occasionally be involved in opportunistic infections.

Ongoing evolution of Chlamydia trachomatis lymphogranuloma venereum: exploring the genomic diversity of circulating strains.

Lymphogranuloma venereum (LGV), the invasive infection of the sexually transmissible infection (STI) Chlamydia trachomatis, is caused by strains from the LGV biovar, most commonly represented by ompA-genotypes L2b and L2. We investigated the diversity in LGV samples across an international collection over seven years using typing and genome sequencing. LGV-positive samples (n=321) from eight countries collected between 2011 and 2017 (Spain n=97, Netherlands n=67, Switzerland n=64, Australia n=53, Sweden n=37, Hungary n=31, Czechia n=30, Slovenia n=10) were genotyped for pmpH and ompA variants. All were found to contain the 9 bp insertion in the pmpH gene, previously associated with ompA-genotype L2b. However, analysis of the ompA gene shows ompA-genotype L2b (n=83), ompA-genotype L2 (n=180) and several variants of these (n=52; 12 variant types), as well as other/mixed ompA-genotypes (n=6). To elucidate the genomic diversity, whole genome sequencing (WGS) was performed from selected samples using SureSelect target enrichment, resulting in 42 genomes, covering a diversity of ompA-genotypes and representing most of the countries sampled. A phylogeny of these data clearly shows that these ompA-genotypes derive from an ompA-genotype L2b ancestor, carrying up to eight SNPs per isolate. SNPs within ompA are overrepresented among genomic changes in these samples, each of which results in an amino acid change in the variable domains of OmpA (major outer membrane protein, MOMP). A reversion to ompA-genotype L2 with the L2b genomic backbone is commonly seen. The wide diversity of ompA-genotypes found in these recent LGV samples indicates that this gene is under immunological selection. Our results suggest that the ompA-genotype L2b genomic backbone is the dominant strain circulating and evolving particularly in men who have sex with men (MSM) populations.

Cutibacterium modestum and "Propionibacterium humerusii" represent the same species that is commonly misidentified as Cutibacterium acnes.

Cutibacterium spp. play an increasing role in soft tissue and implant-associated infections. We isolated a novel Cutibacterium spp. from an implant and investigated this isolate using multiple identification approaches. Correct identification was hampered by inconsistent reference data. The isolate was characterised using conventional methods such as Gram stain, MALDI-TOF MS, and antimicrobial susceptibility testing against multiple antimicrobials. Partial 16S rRNA gene sequencing and whole genome sequencing were also performed. In addition, we summarised the available published sequence data and compared prior data to our strain. Conventional phenotypic identification of our isolate resulted in Cutibacterium spp. After analysis of 16S rRNA gene and genome sequences, our isolate was identified as C. modestum, a very recently described species. The 16S rRNA gene analysis was hampered by three incorrect nucleotides within the 16S rRNA gene reference sequence of C. modestum M12T (accession no. LC466959). We also clearly demonstrate that this novel species is identical to tentatively named "Propionibacterium humerusii". Retrospective data analysis indicates that C. modestum is a clinically important Cutibacterium species often misidentified as C. acnes. The isolation and identification of Cutibacterium spp. is still a challenge. The correct description of very recently named C. modestum and the availability of a correct 16S rRNA sequence of the type strain may help to clarify the taxonomical uncertainty concerning "P. humerusii". The novel C. modestum is an additional, clinically important species within the genus Cutibacterium and may represent a new member of the human skin microbiome.

Unexpectedly High False-Positive Rates for Haemophilus influenzae Using a Meningoencephalitis Syndromic PCR Panel in Two Tertiary Centers.

False-positive results in the diagnostic of meningitis and encephalitis pose important challenges. This study aimed to determine false-positive rates for Haemophilus influenzae in cerebrospinal fluids evaluated by the BioFire FilmArray® Meningitis/Encephalitis Panel. We conducted a retrospective study of all H. influenzae-positive FilmArray®. Meningitis/Encephalitis Panel results from June 2016 to October 2019 in two Swiss university hospitals. Cases were classified as true positive, likely true-positive, and likely false-positive results according to cerebrospinal fluid culture, H. influenzae-specific quantitative real-time PCR (qPCR), and Gram staining, as well as culture of other materials. We performed 3,082 panels corresponding to 2,895 patients: 0.6% of the samples (18/3,082) were positive for H. influenzae. Culture and H. influenzae-specific qPCR were performed on 17/18 (94.4%) and 3/18 (16.7%) cerebrospinal fluid samples, respectively; qPCR was negative in all cases. Among 17 samples sent for culture, 10 concerned patients were not treated with antibiotics prior to lumbar puncture. Only 1/17 revealed growth of H. influenzae and was classified as a true positive. We further classified 3/18 (16.7%) cases with the identification of Gram-negative rods in the cerebrospinal fluid or positive blood cultures for H. influenzae as likely true-positive and 14/18 (77.8%) cases as likely false-positive. Diagnostic results should always be interpreted together with the clinical presentation, cerebrospinal fluid analysis, and other available microbiological results. All H. influenzae-positive results should be viewed with special caution and a H. influenzae-specific qPCR should be systematically considered.

First case of IMP-15-producing Pseudomonas aeruginosa in Switzerland: Challenging laboratory diagnosis using whole genome sequencing (WGS).

We report on the first case of multiresistant Pseudomonas aeruginosa harbouring the metallo-ß-lactamase IMP-15 isolated in Switzerland from a patient repatriated from Cambodia. The laboratory diagnosis of IMP-15 was hampered by two negative tests for carbapenemase detection. The carbapenemase gene was subsequently detected by whole genome sequencing and the isolate further characterised by various phenotypic and genotypic analyses.

Multicenter Prevalence Study Comparing Molecular and Toxin Assays for Clostridioides difficile Surveillance, Switzerland.

Public health authorities in the United States and Europe recommend surveillance for Clostridioides difficile infections among hospitalized patients, but differing diagnostic algorithms can hamper comparisons between institutions and countries. We compared surveillance based on detection of C. difficile by PCR or enzyme immunoassay (EIA) in a nationwide C. difficile prevalence study in Switzerland. We included all routinely collected stool samples from hospitalized patients with diarrhea in 76 hospitals in Switzerland on 2 days, 1 in winter and 1 in summer, in 2015. EIA C. difficile detection rates were 6.4 cases/10,000 patient bed-days in winter and 5.7 cases/10,000 patient bed-days in summer. PCR detection rates were 11.4 cases/10,000 patient bed-days in winter and 7.1 cases/10,000 patient bed-days in summer. We found PCR used alone increased reported C. difficile prevalence rates by <80% compared with a 2-stage EIA-based algorithm.

Brief validation of the novel GeneXpert Xpress SARS-CoV-2 PCR assay.

The clinical and epidemiologic management of the SARS-CoV-2 pandemic is critically dependent on molecular assays with short turn-around time. We validated the novel Xpert Xpress SARS-CoV-2 assay using a commercial nucleic acid testing (Roche Cobas 6800). We found an excellent concordance over a range of SARS-CoV-2 loads and across established human coronaviruses.

Results of the phase I open label clinical trial SAKK 06/14 assessing safety of intravesical instillation of VPM1002BC, a recombinant mycobacterium Bacillus Calmette Guérin (BCG), in patients with non-muscle invasive bladder cancer and previous failure of conventional BCG therapy.

Background: VPM1002BC is a modified mycobacterium Bacillus Calmette Guérin (BCG) for the treatment of non-muscle invasive bladder cancer (NMIBC). The genetic modifications are expected to result in better immunogenicity and less side effects. We report on patient safety and immunology of the first intravesical application of VPM1002BC in human. Methods: Six patients with BCG failure received a treatment of 6 weekly instillations with VPM1002BC. Patients were monitored for adverse events (AE), excretion of VPM1002BC and cytokines, respectively. Results: No DLT (dose limiting toxicity) occurred during the DLT-period. No grade ≥3 AEs occurred. Excretion of VPM1002BC in the urine was limited to less than 24 hours. Plasma levels of TNFα significantly increased after treatment and blood-derived CD4+ T cells stimulated with PPD demonstrated significantly increased intracellular GM-CSF and IFN expression. Conclusion: The intravesical application of VPM1002BC is safe and well tolerated by patients and results in a potential Th1 weighted immune response.

Tick-Borne Relapsing Fever Caused by Borrelia persica in Traveler to Central Asia, 2019.

We report a case of tick-borne relapsing fever caused by Borrelia persica in a traveler returning to Switzerland from central Asia. After the disease was diagnosed by blood smear microscopy, the causative Borrelia species was confirmed by shotgun metagenomics sequencing. PCR and sequencing techniques provide highly sensitive diagnostic tools superior to microscopy.