Epidemiological Link Research Articles

Social-behavioral insights in understanding tuberculosis transmission pattern during the COVID-19 pandemic period in Kuala Lumpur, Malaysia: The MyTBNet study protocol.

Many countries have reported increase of TB incidence during the COVID-19 pandemic period, which demands dire attention as it may threaten global effort to end TB transmission. Services, are among many others, were disrupted by the COVID-19 pandemic during the years 2020 and 2021; but its impact on the TB transmission is not well understood. This retrospective population-based molecular and epidemiological cohort study aims to determine the pattern of TB transmission in Kuala Lumpur (an area with high population density, moderate TB burden and high rates of COVID-19 cases) for the cohort of Pulmonary TB (PTB) cases notified from 2020 until 2021 and factors associated with clustering or clear epidemiologic linkage. This study will be carried out from 2022 until 2024. The study will utilise comparative phylogenetic analysis to determine the degree of relatedness between different isolates, based on the genomes similarities, and overlay this with epidemiological, clinical and social network data to enhance understanding of the social-behavioural dynamics of TB transmission. Mycobacterium tuberculosis complex (MTBC) cultures will be genotyped using Mycobacterial Interspersed Repetitive Unit Variable Number Tandem Repeats (MIRU-VNTR) and whole-genome sequence (WGS) for MTBC cluster isolates. Epidemiologic and genomic data will be overlaid on a social network constructed by means of interviews with patients, by using Social Network Analysis questionnaire, to determine the origins and transmission dynamics of the outbreak. The finding of this study would aid in the identification of TB transmission events, facilitating active case finding, TB screening, TB contact tracing, and the mapping of social contacts during critical period. This will contribute to building an effective preventive and preparedness strategy to interrupt TB transmission in Malaysia, tailored to the characteristics of the local population.

Spatiotemporal and Species‐Crossing Transmission Dynamics of Subclade 2.3.4.4b H5Nx HPAIVs

Subclade 2.3.4.4b H5Nx highly pathogenic avian influenza (HPAI) viruses, emerged in 2013 with multiple subtypes of H5N8, H5N1, and H5N6, had unprecedently caused a global epizootic by H5N1 since 2021, which had devasted multiple species of wild birds, poultry, and wild mammals (terrestrial and marine) with a high mortality, causing severe ecological damage. The infected wild mammals may become new “mixers” for influenza viruses, posing the potential transmission to human. Frequent outbreaks of subclade 2.3.4.4b H5Nx viruses among wild birds and poultry had exposed major gaps in our knowledge on their evolution, spatiotemporal diffusion, and species‐crossing transmission. Here, we integrated the phylogenetic and epidemiological data of subclade 2.3.4.4b H5Nx viruses in public database and used Bayesian phylodynamic analysis to reveal the pattern of the global large‐scale transmission. Phylogenic analysis demonstrated that the HA gene of these viruses diverged into two dominant clusters around 2015 and 2016. The Bayesian phylodynamic analysis illustrated that the viruses presented spatiotemporally complex transmission network with geographical and host relative expansion and recombination with different subtypes of NA segment. Spatially, the Russian Federation (Siberia) was identified as the primary hub for virus transmission, which was further facilitated by the establishment of strong epidemiological linkages between West Europe and broader regions, such as North America. As for hosts, wild Anseriformes were the primary species for the virus spillover, contributing to the spatial expansion and rapid diffusion globally of subclade 2.3.4.4b viruses. We investigated the phylogeny of subclade 2.3.4.4b H5Nx viruses and the spatiotemporal pattern of transmission with initial location and the primary host, which could provide comprehensive insights for subclade 2.3.4.4b H5Nx viruses. Due to the wild birds involved the widespread of subclade 2.3.4.4b H5Nx viruses, the epizootics in poultry are inevitable, so we highly recommend to apply the policy of culling plus with vaccination to protect the poultry industry and potentially protect the public health.

High-Throughput Short Sequence Typing Schemes for Pseudomonas aeruginosa and Stenotrophomonas maltophilia Pure Culture and Environmental DNA.

Molecular typing techniques are utilized to determine genetic similarities between bacterial isolates. However, the use of environmental DNA profiling to assess epidemiologic links between patients and their environment has not been fully explored. This work reports the development and validation of two high-throughput short sequence typing (HiSST) schemes targeting the opportunistic pathogens Pseudomonas aeruginosa and Stenotrophomonas maltophilia, along with a modified SM2I selective medium for the specific isolation of S. maltophilia. These HiSST schemes are based on four discriminative loci for each species and demonstrate high discriminating power, comparable to pairwise whole-genome comparisons. Each scheme includes species-specific PCR primers for precise differentiation from closely related taxa, without the need for upstream culture-dependent methods. For example, the primers targeting the bvgS locus make it possible to distinguish P. aeruginosa from the very closely related Pseudomonas paraeruginosa sp. nov. The selected loci included in the schemes are adapted to massive parallel amplicon sequencing technology. An R-based script implemented in the DADA2 pipeline was assembled to facilitate HiSST analyses for efficient and accurate genotyping of P. aeruginosa and S. maltophilia. We demonstrate the performance of both schemes through in silico validations, assessments against reference culture collections, and a case study involving environmental samples.

Dynamics of Staphylococcus aureus in patients and the hospital environment in a tertiary care hospital in the Netherlands

BackgroundThe dynamics of Staphylococcus aureus in patients and the hospital environment are relatively unknown. We studied these dynamics in a tertiary care hospital in the Netherlands.MethodsNasal samples were taken from adult patients at admission and discharge. Isolates cultured from clinical samples taken before and during hospitalization from these patients were included. Environmental samples of patient rooms were taken over a three-year period. Finally, isolates from clinical samples from patients with an epidemiological link to S. aureus positive rooms were included. Staphylococcal protein A (spa) typing was performed.ResultsNasal samples were taken from 673 patients. One hundred eighteen (17.5%) were positive at admission and discharge, 15 (2.2%) patients acquired S. aureus during hospitalization. Nineteen patients had a positive clinical sample during hospitalization, 15.9% of the S. aureus were considered as from an exogenous source. One hundred and forty (2.8%) environmental samples were S. aureus positive. No persistent contamination of surfaces was observed. Isolates were highly diverse: spa typing was performed for 893 isolates, identifying 278 different spa types, 161 of these spa types were observed only once.ConclusionLimited transmission could be identified between patients and the hospital environment, and from patient-to-patient. Exogenous acquisition was assumed to occur in 15% of clinical samples. Environmental contamination was infrequent, temporarily, and coincided with the strain from the patient admitted to the room at that time. MRSA was rare and not found in the environment.

Prolonged carriage of OXA-244-carbapenemase-producing Escherichia coli complicates epidemiological investigations

The rapid increase of OXA-244-producing Escherichia coli, predominantly driven by genetically clustered isolates of sequence type (ST)38, has been observed in at least nine European countries, including Germany. However, the reasons for the spread of OXA-244-producing E. coli remain unclear. Here, we aim to evaluate the possibility of prolonged carriage. We identified a total of six different patients with repeated detection of OXA-244-producing E. coli isolates, which were subjected to both short and long-read whole-genome sequencing (WGS). Besides allelic differences using core genome multilocus sequence typing (cgMLST) analyses, we obtained numbers of single-nucleotide polymorphisms (SNPs) to calculate individual base-pair substitution (BPS) rates. To assess possible re-exposure and risk factors for prolonged carriage, case interviews were conducted. The time between detections ranged from eleven months to more than three years. Initial isolates originated in three+ out of six cases from clinical samples, whereas remaining samples were from screening, mostly in the inpatient setting. As expected, cgMLST analyses showed low numbers of allelic differences between isolates of each case ranging from 1 to 4, whereas numbers of SNPs were between 2 and 99 (mean = 36), thus clearly highlighting the discrepancy between these different bacterial typing approaches. For five out of six cases, observed BPS rates suggest that patients can be colonized with OXA-244-producing E. coli, including ST38 cluster isolates, for extensively long times. Thus, we may have previously missed the epidemiological link between cases because exposure to OXA-244-producing E. coli could have occurred in a time frame, which has not been evaluated in previous investigations. Our results may help to guide future epidemiological investigations as well as to support the interpretation of genetic diversity of OXA-244-producing E. coli, particularly among ST38 cluster isolates.

Health-related quality of life among prostate cancer survivors with metastatic disease and non-metastatic disease and men without a cancer history in the USA.

Few studies have comprehensively compared health-related quality of life (HRQoL) between metastatic prostate cancer survivors, survivors with non-metastatic disease, and men without a cancer history. We used the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey (SEER-MHOS) data linkage to identify men aged ≥ 65 years enrolled in Medicare Advantage (MA) plans. Prostate cancer survivors were diagnosed between 1988 and 2017 and completed MHOS surveys between 1998 and 2019. We analyzed data from752 metastatic prostate cancer survivors (1040 survey records), 19,583 localized or regional prostate cancer survivors (non-metastatic; 30,121 survey records), and 784,305 men aged ≥ 65 years without a cancer history in the same SEER regions (1.15 million survey records). We used clustered linear regressions to compare HRQoL measures at the person-level using the Veterans RAND 12 Item Health Survey (VR-12) T-scores for general health and physical and mental component summaries. Compared to men without a cancer history, prostate cancer survivors were older, more likely to be married, and had higher socioeconomic status. Compared to men without a cancer history, metastatic prostate cancer survivors reported lower general health (T-score differences [95% confidence interval]: - 6.26, [- 7.14, - 5.38], p < .001), physical health (- 4.33, [- 5.18, - 3.48], p < .001), and mental health (- 2.64, [- 3.40, - 1.88], p < .001) component summaries. Results were similar for other VR-12 T-scores. In contrast, non-metastatic prostate cancer survivors reported similar VR-12 T-scores as men without a cancer history. Further analyses comparing metastatic and non-metastatic prostate cancer survivors support these findings. Interventions to improve health-related quality of life for men diagnosed with metastatic prostate cancer merit additional investigation. Interventions to improve health-related quality of life for metastatic prostate cancer survivors merit additionalinvestigation.

Endothelial lipid droplets suppress eNOS to link high fat consumption to blood pressure elevation.

Metabolic syndrome, today affecting more than 20% of the US population, is a group of 5 conditions that often coexist and that strongly predispose to cardiovascular disease. How these conditions are linked mechanistically remains unclear, especially two of these: obesity and elevated blood pressure. Here, we show that high fat consumption in mice leads to the accumulation of lipid droplets in endothelial cells throughout the organism and that lipid droplet accumulation in endothelium suppresses endothelial nitric oxide synthase (eNOS), reduces NO production, elevates blood pressure, and accelerates atherosclerosis. Mechanistically, the accumulation of lipid droplets destabilizes eNOS mRNA and activates an endothelial inflammatory signaling cascade that suppresses eNOS and NO production. Pharmacological prevention of lipid droplet formation reverses the suppression of NO production in cell culture and in vivo and blunts blood pressure elevation in response to a high-fat diet. These results highlight lipid droplets as a critical and unappreciated component of endothelial cell biology, explain how lipids increase blood pressure acutely, and provide a mechanistic account for the epidemiological link between obesity and elevated blood pressure.

Maintaining measles elimination status in Colombia during outbreak control, 2019Manutenção do status de eliminação do sarampo na Colômbia durante o controle de surtos, 2019

Describe measles outbreaks caused by importation of multiple cases, and the corresponding control interventions. Descriptive study of measles outbreaks caused by the importation of multiple cases to Colombia in 2018-2019. Case definitions, classification of source of infection, collection of biological specimens, searches for suspected cases, case identification, and contact tracing were employed. Vaccination records were obtained from vaccination cards or from the Colombian information system. Nationality was determined from records found in the public health surveillance system. The incident command system was used, and response teams and action plans were activated to control outbreaks. In March 2018, the first case of measles imported from Venezuela was confirmed. Measles incidence in 2018 was 0.2 cases per 100 000 population, and it was 0.3 per 100 000 in 2019. The case fatality rate in 2019 was 0.4%. A total of 214 cases were confirmed in the Venezuelan population (91% with no vaccination history); and 69 outbreaks with no epidemiological link were studied. The MVi/Hulu Langat.MYS/26.11[D8] lineage was identified. Endemic circulation was prevented through innovative interventions such as infection surveillance and control, immediate notification, prioritization of field visits, and transmission risk level criteria. Colombia controlled measles outbreaks that resulted from imported cases, and it prevented endemic circulation, thereby maintaining certification of measles elimination in the country.

Whole-genome sequencing of extensively drug-resistant Salmonella enterica serovar Typhi clinical isolates from the Peshawar region of Pakistan

BackgroundTyphoid fever, caused by Salmonella enterica serovar Typhi, is a significant public health concern due to the escalating of antimicrobial resistance (AMR), with limited treatment options for extensively drug-resistant (XDR) S. Typhi strains pose a serious threat to disease management and control. This study aimed to investigate the genomic characteristics, epidemiology and AMR genes of XDR S. Typhi strains from typhoid fever patients in Pakistan. MethodologyWe assessed 200 patients with enteric fever symptoms, confirming 65 S. Typhi cases through culturing and biochemical tests. Subsequent antimicrobial susceptibility testing revealed 40 cases of extensively drug-resistant (XDR) and 25 cases of multi-drug resistance (MDR). Thirteen XDR strains were selected for whole-genome sequencing, to analyze their sequence type, phylogenetics, resistance genes, pathogenicity islands, and plasmid sequences using variety of data analysis resources. Pangenome analysis was conducted for 140 XDR strains, including thirteen in-house and 127 strains reported from other regions of Pakistan, to assess their genetic diversity and functional annotation. ResultsMLST analysis classified all isolates as sequence type 1 (ST-1) with 4.3.1.1. P1 genotype characterization. Prophage and Salmonella Pathogenicity Island (SPI) analysis identified intact prophages and eight SPIs involved in Salmonella's invasion and replication within host cells. Genome data analysis revealed numerous AMR genes including dfrA7, sul1, qnrS1, TEM-1, Cat1, and CTX-M-15, and SNPs associated with antibiotics resistance. IncY, IncQ1, pMAC, and pAbTS2 plasmids, conferring antimicrobial resistance, were detected in a few XDR S. Typhi strains. Phylogenetic analysis inferred a close epidemiological linkage among XDR strains from different regions of Pakistan. Pangenome was noted closed among these strains and functional annotation highlighted genes related to metabolism and pathogenesis. ConclusionThis study revealed a uniform genotypic background among XDR S. Typhi strains in Pakistan, signifying a persistence transmission of a single, highly antibiotic-resistant clone. The closed pan-genome observed underscores limited genetic diversity and highlights the importance of genomic surveillance for combating drug-resistant typhoid infections.

A genetic and proteomic approach to understanding neuropsychiatric symptoms in ADRD

AbstractBackgroundThree lines of epidemiologic evidence link several psychiatric disorders to ADRD. First, experiencing schizophrenia or a mood/anxiety disorder in early/mid‐adulthood increases the risk of developing dementia by 6‐folds. Second, approximately 80% of ADRD patients experience neuropsychiatric symptoms (NPS), including depression, apathy, anxiety, irritability, agitation, delusions, and hallucinations. Third, these NPS overlap with symptoms of schizophrenia and mood/anxiety disorders. Given these observations, this study focuses on the question of whether these psychiatric disorders and ADRD have shared pathophysiology, which may underlie the manifestation of NPS in ADRDMethodTo investigate whether there is a shared genetic and molecular basis between the psychiatric conditions (major depressive disorder [MDD], bipolar disorder [BD], neuroticism, anxiety, PTSD, schizophrenia, and alcoholism) and ADRD (AD, Lewy body dementia [LBD], ALS, Parkinson’s disease [PD]), we performed three analyses. First, we examined genetic correlations between a psychiatric disorder and an ADRD using GWAS results in each condition and LDSC regression. Second, to identify causal genes and proteins for each of these brain conditions, we integrated each GWAS results with human brain proteomes (n = 722) using multiple independent state‐of‐the‐art integration approaches (PWAS, Mendelian randomization, colocalization analysis). Third, we examined protein‐protein interactions (PPIs) between a psychiatric causal protein and an ADRD causal protein using BIOGRID database.ResultFrom LDSC regression, we found 7 pairs of a psychiatric condition and an ADRD having significant genetic correlations, suggesting a shared genetic diathesis between these psychiatric conditions (MDD, BD, neuroticism, anxiety, PTSD, alcoholism) and ADRD (AD, LBD, ALS). Furthermore, among the causal proteins we identified for each condition, 30% of the ADRD causal proteins (13 of 42) were also causal proteins in the psychiatric conditions, highlighting a shared pathophysiology. Moreover, we found 2.6‐folds more PPIs between a psychiatric causal protein and an ADRD causal protein than by chance (p = 0.003, 120 PPIs).ConclusionTogether, these 3 levels of novel evidence highlight a shared genetic and molecular basis between several psychiatric conditions and ADRD, which may underlie the pathophysiology of NPS in ADRD. The 13 shared causal proteins are promising targets for further validation in NPS in ADRD and towards the goal of developing effective therapeutics for NPS.

A rare presentation of measles and post-measles complications in a neonate: case report

BackgroundMeasles is a common infection in children. Measles infection in children less than 6 months of age is very rare since maternal antibodies play a major role in the prevention of the disease.Case presentationHere we present a rare case of a 34-day-old infant, who had a history of fever with a rash on the 18th day of life and significant history of measles contact with mother and elder brother. The patient presented to us with septic shock and multiorgan involvement in the form of pneumonia, acute gastroenteritis with severe dehydration, mucopurulent conjunctivitis, and post-measles encephalitis. The patient had a strong measles contact and epidemiological linkage to the measles epicenter, Govandi (a locality in the Mumbai region of western India), so measles IgM antibody was obtained which were significantly raised.The patient was successfully revived from this critical presentation with early and appropriate resuscitation, timely ionotropic support, and the use of empirical broad-spectrum antibiotics. The patient required intensive unit care for four days and was started on feeds and discharged after 12 days of hospital stay. On follow-up, the patient is doing well and gaining weight.ConclusionUncommon presentation and the epidemiology of the disease should alert the clinician of having a high index of suspicion. Early intervention and prompt treatment can help reduce morbidity and mortality.

An outbreak of Salmonella Typhimurium associated with the consumption of raw liver at an Eid al-Adha celebration in Wales (UK), July 2021.

In July 2021, Public Health Wales received two notifications of salmonella gastroenteritis. Both cases has attended the same barbecue to celebrate Eid al-Adha, two days earlier. Additional cases attending the same barbecue were found and an outbreak investigation was initiated. The barbecue was attended by a North African community's social network. On same day, smaller lunches were held in three homes in the social network. Many people attended both a lunch and the barbecue. Cases were defined as someone with an epidemiological link to the barbecue and/or lunches with diarrhoea and/or vomiting with date of onset following these events. We undertook a cohort study of 36 people attending the barbecue and/or lunch, and a nested case-control study using Firth logistic regression. A communication campaign, sensitive towards different cultural practices, was developed in collaboration with the affected community. Consumption of a traditional raw liver dish, 'marrara', at the barbecue was the likely vehicle for infection (Firth logistic regression, aOR: 49.99, 95%CI 1.71-1461.54, p = 0.02). Meat and offal came from two local butchers (same supplier) and samples yielded identical whole genome sequences as cases. Future outbreak investigations should be relevant to the community affected by considering dishes beyond those found in routine questionnaires.

2329. What Causes a Cluster to Grow? Factors Associated with a Nosocomial COVID-19 Cluster at a University Hospital in Central Tokyo

Abstract Background Coronavirus disease 2019 (COVID-19) remains a significant threat to hospital infection control. Despite the decrease in severity and mortality associated with changes in the variants of concern and increased vaccination, SARS-CoV-2 transmissibility remains high, and nosocomial clusters continue to be reported in various countries. Although COVID-19 may be detected in multiple patients and healthcare workers (HCWs) in a given ward within a few days, it is uncertain whether these cases will develop into a large cluster. Methods The present, retrospective cohort study of nosocomial COVID-19 clusters was conducted at Tokyo Medical and Dental University Hospital from January 2022 to January 2023 using data from the hospital’s infection prevention and control team. A nosocomial COVID-19 cluster was defined as consisting of more than 2 COVID-19 cases occurring within 5 days in the same ward. Cases with a clear epidemiological link and clusters outside the ward were excluded. We collected information regarding community trends, the index case details, and each cluster's ward profile. Predictors of cluster expansion to more than 5 cases were also examined. Results 66 clusters were identified at the hospital during the study period. The median number of COVID-19 cases per cluster was 3 (range: 2-22), and their median duration was 5 days (range: 1-27). 37 (56.1%), 25 (37.9%), and 4 (6.1%) clusters comprised both inpatients and HCWs, only HCWs, and only patients, respectively. The index case of 51 clusters (77.3%) was a HCW. 18 (27.3%) and 47 (72.7%) clusters contained &amp;gt; 5 and &amp;lt; 5 cases, respectively. No significant intergroup difference was found in terms of community prevalence, index case and ward characteristics, the rate of close contact or history of previous clusters. However, “clusters occurring during the non-epidemic period” and “infections &amp;gt; 3 occurring within 3 days” tended to develop into clusters containing more than 5 cases. Conclusion Nosocomial clusters can occur anywhere, and predicting them is challenging. Further research is needed to identify the factors leading to cluster development and to establish effective infection prevention and control measures. Disclosures All Authors: No reported disclosures

Genomic transmission clusters and circulating lineages of Mycobacterium tuberculosis among refugees residing in refugee camps in Ethiopia

BackgroundUnderstanding the transmission dynamics of Mycobacterium tuberculosis (Mtb) could benefit the design of tuberculosis (TB) prevention and control strategies for refugee populations. Whole Genome Sequencing (WGS) has not yet been used to document the Mtb transmission dynamics among refugees in Ethiopia. We applied WGS to accurately identify transmission clusters and Mtb lineages among TB cases in refugee camps in Ethiopia. Method and designWe conducted a cross-sectional study of 610 refugees in refugee camps in Ethiopia presenting with symptoms of TB. WGS data of 67 isolates was analyzed using the Maximum Accessible Genome for Mtb Analysis (MAGMA) pipeline; iTol and FigTree were used to visualize phylogenetic trees, lineages, and the presence of transmission clusters. ResultsMtb culture-positive refugees originated from South Sudan (52/67, 77.6%), Somalia (9/67, 13.4%). Eritrea (4/67, 6%), and Sudan (2/67, 3%). The majority (52, 77.6%) of the isolates belonged to Mtb lineage (L) 3, and one L9 was identified from a Somalian refugee. The vast majority (82%) of the isolates were pan-susceptible Mtb, and none were multi-drug-resistant (MDR)-TB. Based on the 5-single nucleotide polymorphisms cutoff, we identified eight potential transmission clusters containing 23.9% of the isolates. Contact investigation confirmed epidemiological links with either family or social interaction within the refugee camps or with neighboring refugee camps. ConclusionFour lineages (L1, L3, L4, and L9) were identified, with the majority of strains being L3, reflecting the Mtb L3 dominance in South Sudan, where the majority of refugees originated from. Recent transmission among refugees was relatively low (24%), likely due to the short study period. The improved understanding of the Mtb transmission dynamics using WGS in refugee camps could assist in designing effective TB control programs for refugees.

Virulence and resistance patterns of Vibrio cholerae non-O1/non-O139 acquired in Germany and other European countries

Global warming has caused an increase in the emergence of Vibrio species in marine and estuarine environments as well as fresh water bodies. Over the past decades, antimicrobial resistance (AMR) has evolved among Vibrio species toward various antibiotics commonly used for the treatment of Vibrio infections. In this study, we assessed virulence and resistance patterns of Vibrio cholerae non-O1/non-O139 strains derived from Germany and other European countries. A total of 63 clinical and 24 environmental Vibrio cholerae non-O1/non-O139 strains, collected between 2011 and 2021, were analyzed. In silico antibiotic resistances were compared with resistance phenotypes according to EUCAST breakpoints. Additionally, genetic relatedness between isolates was assessed by two cgMLST schemes (SeqSphere +, pubMLST). Both cgMLST schemes yielded similar results, indicating high genetic diversity among V. cholerae non-O1/non-O139 isolates. Some isolates were found to be genetically closely related (allelic distance &amp;lt; 20), which suggests an epidemiological link. Thirty-seven virulence genes (VGs) were identified among 87 V. cholerae non-O1/non-O139 isolates, which resulted in 38 virulence profiles (VPs). VPs were similar between clinical and environmental isolates, with the exception of one clinical isolate that displayed a higher abundance of VGs. Also, a cluster of 11 environmental isolates was identified to have the lowest number of VGs. Among all strains, the predominant virulence factors were quorum sensing protein (luxS), repeats-in-toxins (rtxC/rtxD), hemolysin (hlyA) and different type VI secretion systems (T6SS) genes. The genotypic profiles revealed antibiotic resistance genes (ARGs) associated with resistance to beta-lactams, quinolones, macrolides, tetracycline, antifolate, aminoglycosides, fosfomycin, phenicols and sulfonamide. Carbapenemase gene VCC-1 was detected in 10 meropenem-resistant V. cholerae non-O1/non-O139 isolates derived from surface water in Germany. The proportion of resistance among V. cholerae non-O1/non-O139 species isolates against first line treatment (3rd generation cephalosporin, tetracycline and fluoroquinolone) was low. Empirical treatment would likely have been effective for all of the clinical V. cholerae non-O1/non-O139 isolates examined. Nevertheless, carbapenem-resistant isolates have been present in fresh water in Germany and might represent a reservoir for ARGs. Monitoring antimicrobial resistance is crucial for public health authorities to minimize the risks for the human population.

Mpox knowledge, behaviours and barriers to public health measures among gay, bisexual and other men who have sex with men in the UK: a qualitative study to inform public health guidance and messaging

BackgroundThe 2022-23 mpox epidemic is the first-time sustained community transmission had been reported in countries without epidemiological links to endemic areas. During that period, the outbreak almost exclusively affected sexual networks of gay, bisexual, or other men who have sex with men (GBMSM) and people living with HIV. In efforts to control transmission, multiple public health measures were implemented, including vaccination, contact tracing and isolation. This study examines knowledge, attitudes, and perceptions of mpox among a sample of GBMSM during the 2022-23 outbreak in the UK, including facilitators for and barriers to the uptake of public health measures.MethodsInterviews were conducted with 44 GBMSM between May and December 2022. Data were analysed using reflexive thematic analysis. Positive and negative comments pertaining to public health measures were collated in a modified version of a ‘table of changes’ to inform optimisations to public health messages and guidance.ResultsMost interviewees were well informed about mpox transmission mechanisms and were either willing to or currently adhering to public health measures, despite low perceptions of mpox severity. Measures that aligned with existing sexual health practices and norms were considered most acceptable. Connections to GBMSM networks and social media channels were found to increase exposure to sexual health information and norms influencing protective behaviours. Those excluded or marginalized from these networks found some measures challenging to perform or adhere to. Although social media was a key mode of information sharing, there were preferences for timely information from official sources to dispel exaggerated or misleading information.ConclusionsThere are differential needs, preferences, and experiences of GBMSM that limit the acceptability of some mitigation and prevention measures. Future public health interventions and campaigns should be co-designed in consultation with key groups and communities to ensure greater acceptability and credibility in different contexts and communities.

Molecular Diversity of Mycobacterium avium subsp. paratuberculosis in Four Dairy Goat Herds from Thuringia (Germany).

This study investigated the intra- and inter-herd diversity of Mycobacterium avium subsp. paratuberculosis (MAP) isolates from four goat herds in Thuringia (Germany) that were affected by paratuberculosis for several years. The main focus was on the characterization and distribution of genotypes among animals and the environment of goat herd 1. This study included 196 isolates from the feces of 121 infected goats, various tissues from 13 clinically diseased goats, 29 environmental samples from herd 1, and additionally, 22 isolates of different origin from herds 2 to 4. The isolates, sampled between 2018 and 2022, were genotyped using short-sequence-repeat (SSR) analysis, mycobacterial-interspersed repetitive units-variable-number tandem repeat (MIRU-VNTR) analysis, and a single nucleotide polymorphism (SNP)-based assay for phylogenetic grouping. All the isolates belonged to the MAP-C group. In herd 1, one predominant genotype was determined, while two other genotypes were identified very rarely and only in fecal and environmental samples. One of three further genotypes was found in each of herds 2 to 4. The assignment of genotypes to different phylogenetic clades suggested six different infection strains. The results indicated no epidemiological links between the examined herds. Based on the current MAP genotyping data from Germany, possible sources of infection are MAP-contaminated barns previously used by infected cattle and the purchase of sub-clinically infected goats.

Genomic analysis of Citrobacter from Australian wastewater and silver gulls reveals novel sequence types carrying critically important antibiotic resistance genes

Antimicrobial resistance (AMR) is a major public health concern, and environmental bacteria have been recognized as important reservoirs of antimicrobial resistance genes (ARGs). Citrobacter, a common environmental bacterium and opportunistic pathogen in humans and other animals, has been largely understudied in terms of its diversity and AMR potential. Whole-genome (short-read) sequencing on a total of 77 Citrobacter isolates obtained from Australian silver gull (Chroicocephalus novaehollandiae) (n = 17) and influent wastewater samples (n = 60) was performed, revealing a diverse Citrobacter population, with seven different species and 33 sequence types, 17 of which were novel. From silver gull using non-selective media we isolated a broader range of species with little to no mobilised ARG carriage. Wastewater isolates (selected using Carbapenem- Resistant Enterobacterales (CRE) selective media) carried a heavy burden of ARGs (up to 21 ARGs, conferring resistance to nine classes of antibiotics), with several novel multidrug-resistant (MDR) lineages identified, including C. braakii ST1110, which carried ARGs conferring resistance to eight to nine classes of antibiotics, and C. freundii ST1105, which carried two carbapenemase genes, blaIMP-4 in class 1 integron structure, and blaKPC-2. Additionally, we identified an MDR C. portucalensis isolate carrying blaNDM-1, blaSHV-12, and mcr-9. We identified IncC, IncM2, and IncP6 plasmids as the likely vectors for many of the critically important mobilised ARGs. Phylogenetic analyses were performed to assess any epidemiological linkages between isolation sources, demonstrating low relatedness across sources beyond the ST level. However, these analyses did reveal some closer relationships between strains from disparate wastewater sources despite their collection some 13,000 km apart. These findings support the need for future surveillance of Citrobacter populations in wastewater and wildlife populations to monitor for potential opportunistic human pathogens.

An Autochthonous Susceptible Candida auris Clade I Otomycosis Case in Iran.

Candida auris is a newly emerging multidrug-resistant fungal pathogen considered to be a serious global health threat. Due to diagnostic challenges, there is no precise estimate for the prevalence rate of this pathogen in Iran. Since 2019, only six culture-proven C. auris cases have been reported from Iran, of which, five belonged to clade V and one to clade I. Herein, we report a case of otomycosis due to C. auris from 2017 in a 78-year-old man with diabetes mellitus type II without an epidemiological link to other cases or travel history. Short tandem repeat genotyping and whole genome sequencing (WGS) analysis revealed that this isolate belonged to clade I of C. auris (South Asian Clade). The WGS single nucleotide polymorphism calling demonstrated that the C. auris isolate from 2017 is not related to a previously reported clade I isolate from Iran. The presence of this retrospectively recognized clade I isolate also suggests an early introduction from other regions or an autochthonous presence. Although the majority of reported C. auris isolates worldwide are resistant to fluconazole and, to a lesser extent, to echinocandins and amphotericin B, the reported clade I isolate from Iran was susceptible to all antifungal drugs.

A prospective bacterial whole-genome-sequencing-based surveillance programme for comprehensive early detection of healthcare-associated infection transmission in paediatric oncology patients

Bacterial whole-genome sequencing (WGS) and determination of genetic relatedness is an important tool for investigation of epidemiologically suspected outbreaks. This prospective cohort study evaluated a comprehensive, prospective bacterial WGS-based surveillance programme for early detection of transmission of most bacterial pathogens among patients at a paediatric oncology hospital. Cultured bacterial isolates from clinical diagnostic specimens collected prospectively from both inpatient and outpatient encounters between January 2019 and December 2021 underwent routine WGS and core genome multi-locus sequence typing to determine isolates' relatedness. Previously collected isolates from January to December 2018 were retrospectively analysed for identification of prior or ongoing transmission. Multi-patient clusters were investigated to identify potential transmission events based on temporal and spatial epidemiological links and interventions were introduced. A total of 1497 bacterial isolates from 1025 patients underwent WGS. A total of 259 genetically related clusters were detected, of which 18 (6.9%) multi-patient clusters involving 38 (3.7%) patients were identified. Sixteen clusters involved two patients each, and two clusters involved three patients. Following investigation, epidemiologically plausible transmission links were identified in five (27.8%) multi-patient clusters. None of the multi-patient clusters were suspected by conventional epidemiological surveillance. Bacterial WGS-based surveillance for early detection of hospital transmission detected several limited multi-patient clusters that were unrecognized by conventional epidemiological methods. Genomic surveillance helped efficiently focus interventions while reducing unnecessary investigations.