RCandy: an R package for visualizing homologous recombinations in bacterial genomes

SUMMARY: Homologous recombination is an important evolutionary process in bacteria and other prokaryotes, which increases genomic sequence diversity and can facilitate adaptation. Several methods and tools have been developed to detect genomic regions recently affected by recombination. Exploration and visualization of such recombination events can reveal valuable biological insights, but it remains challenging. Here, we present RCandy, a platform-independent R package for rapid, simple and flexible visualization of recombination events in bacterial genomes. AVAILABILITY AND IMPLEMENTATION: RCandy is an R package freely available for use under the MIT license. It is platform-independent and has been tested on Windows, Linux and MacOSX. The source code comes together with a detailed vignette available on GitHub at https://github.com/ChrispinChaguza/RCandy. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Statistical Regression Model of Water, Sanitation, and Hygiene; Treatment Coverage; and Environmental Influences on School-Level Soil-Transmitted Helminths and Schistosome Prevalence in Kenya: Secondary Analysis of the National Deworming Program Data.

According to the Kenya National School-Based Deworming program launched in 2012 and implemented for the first 5 years (2012-2017), the prevalence of soil-transmitted helminths (STH) and schistosomiasis substantially reduced over the mentioned period among the surveyed schools. However, this reduction is heterogeneous. In this study, we aimed to determine the factors associated with the 5-year school-level infection prevalence and relative reduction (RR) in prevalence in Kenya following the implementation of the program. Multiple variables related to treatment, water, sanitation, and hygiene (WASH) and environmental factors were assembled and included in mixed-effects linear regression models to identify key determinants of the school location STH and schistosomiasis prevalence and RR. Reduced prevalence of Ascaris lumbricoides was associated with low ( 75%) reported coverage of a household improved water source. Reduced Schistosoma haematobium was associated with high aridity index. Analysis indicated that a combination of factors, including the number of treatment rounds, multiple related program interventions, community- and school-level WASH, and several environmental factors had a major influence on the school-level infection transmission and reduction

Pneumococcal within-host diversity during colonization, transmission and treatment

Characterizing the genetic diversity of pathogens within the host promises to greatly improve surveillance and reconstruction of transmission chains. For bacteria, it also informs our understanding of inter-strain competition and how this shapes the distribution of resistant and sensitive bacteria. Here we study the genetic diversity of Streptococcus pneumoniae within 468 infants and 145 of their mothers by deep sequencing whole pneumococcal populations from 3,761 longitudinal nasopharyngeal samples. We demonstrate that deep sequencing has unsurpassed sensitivity for detecting multiple colonization, doubling the rate at which highly invasive serotype 1 bacteria were detected in carriage compared with gold-standard methods. The greater resolution identified an elevated rate of transmission from mothers to their children in the first year of the child's life. Comprehensive treatment data demonstrated that infants were at an elevated risk of both the acquisition and persistent colonization of a multidrug-resistant bacterium following antimicrobial treatment. Some alleles were enriched after antimicrobial treatment, suggesting that they aided persistence, but generally purifying selection dominated within-host evolution. Rates of co-colonization imply that in the absence of treatment, susceptible lineages outcompeted resistant lineages within the host. These results demonstrate the many benefits of deep sequencing for the genomic surveillance of bacterial pathogens. Longitudinal population deep sequencing of Streptococcus pneumoniae sampled from infants and their mothers improves our understanding of the dynamics of colonization, transmission, inter-strain competition and the impact of antibiotic treatment.Peer reviewe

Genomic landscape of extended-spectrum β-lactamase resistance in Escherichia coli from an urban African setting

Objectives: Efforts to treat Escherichia coli infections are increasingly being compromised by the rapid, global spread of antimicrobial resistance (AMR). Whilst AMR in E. coli has been extensively investigated in resource-rich settings, in sub-Saharan Africa molecular patterns of AMR are not well described. In this study, we have begun to explore the population structure and molecular determinants of AMR amongst E. coli isolates from Malawi. Methods: Ninety-four E. coli isolates from patients admitted to Queen’s Hospital, Malawi, were whole-genome sequenced. The isolates were selected on the basis of diversity of phenotypic resistance profiles and clinical source of isolation (blood, CSF and rectal swab). Sequence data were analysed using comparative genomics and phylogenetics. Results: Our results revealed the presence of five clades, which were strongly associated with E. coli phylogroups A, B1, B2, D and F. We identified 43 multilocus STs, of which ST131 (14.9%) and ST12 (9.6%) were the most common. We identified 25 AMR genes. The most common ESBL gene was blaCTX-M-15 and it was present in all five phylogroups and 11 STs, and most commonly detected in ST391 (4/4 isolates), ST648 (3/3 isolates) and ST131 [3/14 (21.4%) isolates]. Conclusions: This study has revealed a high diversity of lineages associated with AMR, including ESBL and fluoroquinolone resistance, in Malawi. The data highlight the value of longitudinal bacteraemia surveillance coupled with detailed molecular epidemiology in all settings, including low-income settings, in describing the global epidemiology of ESBL resistance

Prevalence and Correlation Analysis of Soil-Transmitted Helminths Infections and Treatment Coverage for Preschool and School Aged Children in Kenya: Secondary Analysis of the National School Based Deworming Program Data

Background: Soil-transmitted helminths (STH) are among the most common parasitic infections globally, disproportionately affecting children. Treatment of STH in Kenya is often targeted at preschool (PSAC) and school aged (SAC) children delivered through annual mass drug administration (MDA) in primary schools. Understanding group-specific prevalence and dynamics between treatment and coverage is critical for continued treatment success. This study aims to provide detailed information on group-specific infection prevalence and relative reductions (RR), and their relationships with treatment coverage over time. Additionally, it aims to quantify the correlation between the observed school level infection prevalence and treatment coverage. Methods: Secondary analysis of existing data collected between 2012 and 2018 by the monitoring and evaluation (M&E) program of the National School-Based Deworming (NSBD) program was used. The M&E program conducted surveys utilizing cross-sectional study design, at four survey time points, in a nationally-representative sample of schoolchildren across counties in Kenya. In each participating school, the program randomly sampled 108 children per school, of both groups. Infection prevalence was estimated using binomial regression, RR in prevalence using multivariable mixed effects model, statistical correlations using structural equation modeling, and change-point-analysis using the binary segmentation algorithm. Results: Overall, STH prevalence for PSAC was 33.7, 20.2, 19.0, and 17.9% during Year 1 (Y1), Year 3 (Y3), Year 5 (Y5), and Year 6 (Y6) surveys, respectively with an overall RR of 46.9% (p = 0.001) from Y1 to Y6. Similarly, overall STH prevalence for SAC was 33.6, 18.4, 14.7, and 12.5% during Y1, Y3, Y5, and Y6 surveys, respectively with an overall RR of 62.6% (p < 0.001). An overall (all time points) significant but very weak negative correlation was found between treatment coverage and undifferentiated STH prevalence (r = -0.144, p = 0.002) among PSAC but not in SAC. Further, we observed inter-county heterogeneity variation in infection prevalence, RR, as well as correlations. Conclusion: The analysis showed that after six rounds of MDA, prevalence of STH has significantly declined among both groups of children, however not to a point where it is not a public health problem (below 1%). The analysis, additionally established an overall significant but weak negative correlation between treatment coverage and prevalence, indicating that the current treatment coverage might not be sufficient to drive the overall STH prevalence to below 1%. These findings will allow STH control programs in Kenya to make decisions that will accelerate the attainment of STH elimination as a public health problem

Left Atrial Structure in Relationship to Age, Sex, Ethnicity, and Cardiovascular Risk Factors MESA (Multi-Ethnic Study of Atherosclerosis)

This research was supported by contracts N01-HC-95159, N01-HC-95160, N01-HC-95161, N01- HC-95162, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01- HC-95168 and N01-HC-95169 from the National Heart, Lung, and Blood Institute and by grants UL1-TR-000040 and UL1-TR-001079 from the National Center for Research Resources. Prof. Petersen and Drs. Zemrak and Mohiddin gratefully acknowledge funding from the National Institute for Health Research Cardiovascular Biomedical Research Unit at Barts. Prof. Petersen’s work is supported by awards establishing the Farr Institute of Health Informatics Research at University College London Partners from the Medical Research Council, in partnership with Arthritis Research United Kingdom, the British Heart Foundation, Cancer Research United Kingdom, the Economic and Social Research Council, the Engineering and Physical Sciences Research Council, the National Institute of Health Research, the National Institute for Social Care and Health Research (Welsh Assembly Government), the Chief Scientist Office (Scottish Government Health Directorates), and the Wellcome Trust (MR/K006584/1)

Study protocol: The Intensive Care Outcome Network ('ICON') study

<p>Abstract</p> <p>Background</p> <p>Extended follow-up of survivors of ICU treatment has shown many patients suffer long-term physical and psychological consequences that affect their health-related quality of life. The current lack of rigorous longitudinal studies means that the true prevalence of these physical and psychological problems remains undetermined.</p> <p>Methods/Design</p> <p>The ICON (Intensive Care Outcome Network) study is a multi-centre, longitudinal study of survivors of critical illness. Patients will be recruited prior to hospital discharge from 20–30 ICUs in the UK and will be assessed at 3, 6, and 12 months following ICU discharge for health-related quality of life as measured by the Short Form-36 (SF-36) and the EuroQoL (EQ-5D); anxiety and depression as measured by the Hospital Anxiety and Depression Scale (HADS); and post traumatic stress disorder (PTSD) symptoms as measured by the PTSD Civilian Checklist (PCL-C). Postal questionnaires will be used.</p> <p>Discussion</p> <p>The ICON study will create a valuable UK database detailing the prevalence of physical and psychological morbidity experienced by patients as they recover from critical illness. Knowledge of the prevalence of physical and psychological morbidity in ICU survivors is important because research to generate models of causality, prognosis and treatment effects is dependent on accurate determination of prevalence. The results will also inform economic modelling of the long-term burden of critical illness.</p> <p>Trial Registration</p> <p>ISRCTN69112866</p

The population-level impact of Enterococcus faecalis genetics on intestinal colonization and extraintestinal infection

IMPORTANCE: Enterococcus faecalis causes life-threatening invasive hospital- and community-associated infections that are usually associated with multidrug resistance globally. Although E. faecalis infections cause opportunistic infections typically associated with antibiotic use, immunocompromised immune status, and other factors, they also possess an arsenal of virulence factors crucial for their pathogenicity. Despite this, the relative contribution of these virulence factors and other genetic changes to the pathogenicity of E. faecalis strains remain poorly understood. Here, we investigated whether specific genomic changes in the genome of E. faecalis isolates influence its pathogenicity-infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection and intestinal colonization. Our findings indicate that E. faecalis genetics partially influence the infection of hospitalized and nonhospitalized individuals and the propensity to cause extraintestinal infection, possibly due to gut-to-bloodstream translocation, highlighting the potential substantial role of host and environmental factors, including gut microbiota, on the opportunistic pathogenic lifestyle of this bacterium

Modified Chrispin-Norman chest radiography score for cystic fibrosis: observer agreement and correlation with lung function

Contains fulltext : 96114.pdf ( ) (Closed access)OBJECTIVE: To test observer agreement and two strategies for possible improvement (consensus meeting and reference images) for the modified Chrispin-Norman score for children with cystic fibrosis (CF). METHODS: Before and after a consensus meeting and after developing reference images three observers scored sets of 25 chest radiographs from children with CF. Observer agreement was tested for line, ring, mottled and large soft shadows, for overinflation and for the composite modified Chrispin-Norman score. Correlation with lung function was assessed. RESULTS: Before the consensus meeting agreement between observers 1 and 2 was moderate-good, but with observer 3 agreement was poor-fair. Scores correlated significantly with spirometry for observers 1 and 2 (-0.72<R<-0.42, P < 0.05), but not for observer 3. Agreement with observer 3 improved after the consensus meeting. Reference images improved agreement for overinflation and mottled and large shadows and correlation with lung function, but agreement for the modified Chrispin-Norman score did not improve further. CONCLUSION: Consensus meetings and reference images improve among-observer agreement for the modified Chrispin-Norman score, but good agreement was not achieved among all observers for the modified Chrispin-Norman score and for bronchial line and ring shadows

Genomic analysis of Klebsiella pneumoniae isolates from Malawi reveals acquisition of multiple ESBL determinants across diverse lineages

Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations