Assessment of the quality and quantity of naturally induced antibody responses to EBA175RIII-V in Ghanaian children living in two communities with varying malaria transmission patterns

Abstract Background Recent global reports on malaria suggest significant decrease in disease severity and an increase in control interventions in many malaria endemic countries, including Ghana. However, a major driving force sustaining malaria transmission in recent times is the asymptomatic carriage of malaria parasites, which can enhance immune responses against parasite antigens. This study determined the prevalence and relative avidities of naturally induced antibodies to EBA175RIII–VLl in asymptomatic children living in two communities with varying malaria transmission patterns. Methods An asexual stage Plasmodium falciparum antigen, EBA175RIII–VLl was expressed in Lactococcus lactis, purified and used in indirect ELISA to measure total and cytophilic IgG concentrations and avidities in children aged between 6 and 12 years. The children were selected from Obom and Abura, communities with perennial and seasonal malaria transmission, respectively. Venous blood samples were collected in July and October 2015 and again in January 2016. The multiplicity of infection and the genetic diversity of EBA175RIII circulating in both sites were also assessed using polymerase chain reaction. Results Asymptomatic parasite carriage in the children from Obom decreased from July (peak season), through October and January, however parasite carriage in children from Abura was bimodal, with the lowest prevalence estimated in October. Antibody concentrations over the course of the study remained stable within each study site however, children living in Obom had significantly higher EBA175RIII–VLl antibody concentrations than children living in Abura (P < 0.05, Mann–Whitney test). Over the course of the study, the relative antibody avidities of EBA175RIII–VLl IgG antibodies were similar within and between the sites. Conclusion Naturally acquired IgG concentrations but not relative antibody avidities to EBA175RIII–V were significantly higher in Obom where malaria transmission is perennial than in Abura, where malaria transmission is seasonal

Improving the value of public RNA-seq expression data by phenotype prediction.

Publicly available genomic data are a valuable resource for studying normal human variation and disease, but these data are often not well labeled or annotated. The lack of phenotype information for public genomic data severely limits their utility for addressing targeted biological questions. We develop an in silico phenotyping approach for predicting critical missing annotation directly from genomic measurements using well-annotated genomic and phenotypic data produced by consortia like TCGA and GTEx as training data. We apply in silico phenotyping to a set of 70 000 RNA-seq samples we recently processed on a common pipeline as part of the recount2 project. We use gene expression data to build and evaluate predictors for both biological phenotypes (sex, tissue, sample source) and experimental conditions (sequencing strategy). We demonstrate how these predictions can be used to study cross-sample properties of public genomic data, select genomic projects with specific characteristics, and perform downstream analyses using predicted phenotypes. The methods to perform phenotype prediction are available in the phenopredict R package and the predictions for recount2 are available from the recount R package. With data and phenotype information available for 70,000 human samples, expression data is available for use on a scale that was not previously feasible

Physicians' knowledge, attitudes, and perceptions concerning antibiotic resistance:a survey in a Ghanaian tertiary care hospital

Abstract Background Understanding the knowledge, attitudes and practices of physicians towards antibiotic resistance is key to developing interventions aimed at behavior change. The survey aimed to investigate physicians’ knowledge and attitudes towards antibiotic resistance in a tertiary-care hospital setting in Ghana. Methods We conducted a cross-sectional respondent-driven survey using a 40-item, anonymous, voluntary, traditional paper-and-pencil self-administered questionnaire among 159 physicians at Korle-Bu Teaching Hospital. Single and multi-factor analysis were conducted to assess the study objectives. Results The survey was completed by 159 of 200 physicians (response rate of 79.5%). Of physicians, 30.1% (47/156) perceived antibiotic resistance as very important global problem, 18.5% (29/157) perceived it as very important national problem and only 8.9% (14/157) thought it as a very important problem in their hospital. Methicillin resistant Staphylococcus aureus was the most known about antibiotic resistant bacteria of public health importance followed by extended-spectrum beta-lactamase-producing Enterobacteriaceae, carbapenem resistant Enterobacteriaceae (CRE) and vancomycin resistant enterococci (VRE). In multiple logistic regression analysis, senior physicians were nearly 3 times more likely to know about CRE than junior physicians. The odds of knowing about VRE increased over 4.5 times from being a junior to becoming senior physician. Among junior physicians, age had no associated effect on their knowledge of VRE or CRE. Conclusions Physicians in this survey showed variable knowledge and perceptions on antibiotic resistance. Introducing educational programs on antibiotic resistance would be a useful intervention and should focus on junior physicians

Surveillance of bacterial pathogens of diarrhoea in two selected sub metros within the Accra metropolis

Background: In recent years, many localities within the Greater Accra Region (GAR) have witnessed several episodes of cholera outbreaks, with some deaths.Compared to previous epidemics, which usually followed heavy rains, recent outbreaks show no seasonality.Objectives: To investigate infective bacterial diseases in selected sub metros within the GAR.Methods: We used existing disease surveillance systems in Ghana, and investigated all reported cases of diarrhoea that met our case-definition. A three-daytraining workshop was done prior to the start of study, to sensitize prescribers at the Korle-Bu Polyclinic and Maamobi General hospital. A case-based investigationform was completed per patient, and two rectal swabs were taken for culture at the National Public Health and Reference Laboratory. Serotyping and antibiogramprofiles of identified bacteria were determined. Potential risk factors were also assessed using a questionnaire.Results: Between January and June 2012, a total of 361 diarrhoeal cases with 5 deaths were recorded. Out of a total of 218 rectal swabs cultured, 71 (32.6%) Vibrio cholerae O1 Ogawa serotypes, and 1 (0.5%) Salmonella (O group B) were laboratory confirmed. No Shigella was isolated. The Vibrio cholerae isolates were susceptible to ciprofloxacin and tetracycline. Greater than 80% of patients reported having drank sachet water 24 h prior to diarrhoea onset, and many (144/361) young adults (20-29 years) reported with diarrhoea.Conclusion: Enhanced surveillance of diarrhoeal diseases (enteric pathogens) within cholera endemic regions, will serve as an early warning signal, and reduce fatalities associated with infective diarrhoea.Keywords: Diarrhoeal disease surveillance, enteric pathogens, Vibrio cholerae, Salmonell

Reported exposure to SARS-CoV-2 and relative perceived importance of different settings for SARS-CoV-2 acquisition in England and Wales: Analysis of the Virus Watch Community Cohort [version 1; peer review: awaiting peer review]

We aimed to assess the relative importance of different settings for SARS-CoV-2 transmission in a large community cohort based on perceived location of infection for self-reported confirmed SARS-COV-2 cases. We demonstrate the importance of home, work and education as perceived venues for transmission. In children, education was most important and in older adults essential shopping was of high importance. Our findings support public health messaging about infection control at home, advice on working from home and restrictions in different venues

Highly connected 3D chromatin networks established by an oncogenic fusion protein shape tumor cell identity.

Cell fate transitions observed in embryonic development involve changes in three-dimensional genomic organization that provide proper lineage specification. Whether similar events occur within tumor cells and contribute to cancer evolution remains largely unexplored. We modeled this process in the pediatric cancer Ewing sarcoma and investigated high-resolution looping and large-scale nuclear conformation changes associated with the oncogenic fusion protein EWS-FLI1. We show that chromatin interactions in tumor cells are dominated by highly connected looping hubs centered on EWS-FLI1 binding sites, which directly control the activity of linked enhancers and promoters to establish oncogenic expression programs. Conversely, EWS-FLI1 depletion led to the disassembly of these looping networks and a widespread nuclear reorganization through the establishment of new looping patterns and large-scale compartment configuration matching those observed in mesenchymal stem cells, a candidate Ewing sarcoma progenitor. Our data demonstrate that major architectural features of nuclear organization in cancer cells can depend on single oncogenes and are readily reversed to reestablish latent differentiation programs

Deprivation and exposure to public activities during the COVID-19 pandemic in England and Wales

BACKGROUND: Differential exposure to public activities may contribute to stark deprivation-related inequalities in SARS-CoV-2 infection and outcomes but has not been directly investigated. We set out to investigate whether participants in Virus Watch-a large community cohort study based in England and Wales-reported differential exposure to public activities and non-household contacts during the autumn-winter phase of the COVID-19 pandemic according to postcode-level socioeconomic deprivation. METHODS: Participants (n=20 120-25 228 across surveys) reported their daily activities during 3 weekly periods in late November 2020, late December 2020 and mid-February 2021. Deprivation was quantified based on participants' residential postcode using English or Welsh Index of Multiple Deprivation quintiles. We used Poisson mixed-effect models with robust standard errors to estimate the relationship between deprivation and risk of exposure to public activities during each survey period. RESULTS: Relative to participants in the least deprived areas, participants in the most deprived areas exhibited elevated risk of exposure to vehicle sharing (adjusted risk ratio (aRR) range across time points: 1.73-8.52), public transport (aRR: 3.13-5.73), work or education outside of the household (aRR: 1.09-1.21), essential shops (aRR: 1.09-1.13) and non-household contacts (aRR: 1.15-1.19) across multiple survey periods. CONCLUSION: Differential exposure to essential public activities-such as attending workplaces and visiting essential shops-is likely to contribute to inequalities in infection risk and outcomes. Public health interventions to reduce exposure during essential activities and financial and practical support to enable low-paid workers to stay at home during periods of intense transmission may reduce COVID-related inequalities

Inequalities in access to paid sick leave among workers in England and Wales

Background: It is poorly understood which workers lack access to sick pay in England and Wales. This evidence gap has been of particular interest in the context of the Covid-19 pandemic given the relationship between presenteeism and infectious disease transmission. // Method: This cross-sectional analysis (n = 8874) was nested within a large community cohort study based across England and Wales (Virus Watch). An online survey in February 2021 asked participants in work if they had access to paid sick leave. We used logistic regression to examine sociodemographic factors associated with lacking access to sick pay. // Results: Only 66% (n = 5864) of participants reported access to sick pay. South Asian workers (adjusted odds ratio [OR] 1.40, 95% confidence interval [CI] 1.06–1.83) and those from Other minority ethnic backgrounds (OR 2.93, 95% CI 1.54–5.59) were more likely to lack access to sick pay compared to White British workers. Older workers (OR range 1.72 [1.53–1.93]–5.26 [4.42–6.26]), workers in low-income households (OR 2.53, 95% CI 2.15–2.98) and those in transport, trade, and service occupations (OR range 2.03 [1.58–2.61]–5.29 [3.67–7.72]) were also more likely to lack access to sick pay compared respectively to workers aged 25–44, those in high income households and managerial occupations. // Discussion: Unwarranted age and ethnic inequalities in sick pay access are suggestive of labour market discrimination. Occupational differences are also cause for concern. Policymakers should consider expanding access to sick pay to mitigate transmission of Covid-19 and other endemic respiratory infections in the community, and in the context of pandemic preparation

Prevalence of Asymptomatic Malaria among Children in the Tamale Metropolis: How Does the PfHRP2 CareStart™ RDT Perform against Microscopy?

Background. Asymptomatic carriage of the malaria parasites, likewise its misdiagnosis, especially false negatives, due to the use of substandard rapid diagnosis tests (RDTs) has been shown to hinder the progress of the fight against malaria. Method. The study assessed the prevalence of asymptomatic malaria as well as the performance of Plasmodium falciparum-specific protein and histidine-rich protein 2 (PfHRP2) CareStart™ RDT against standard microscopy in the detection of malaria infection among 345 children (1-15 yrs) from two (2) basic schools in Tamale Metropolis. Results. From the microscopy (considered as gold standard), prevalence of malaria among the asymptomatic children was found to be 2.6%, with sensitivity and specificity of CareStart™ RDT in detecting P. falciparum infections found to be 55.6% and 93.8%, respectively. The positive predictive value (PPV) and negative predictive value (NPV) of CareStart™ RDT were found to be 19.23% and 98.45%, respectively. There was an evidence showing a significant relation between CareStart™ RDT and microscopy in determining malaria infection (χ2 = 30.579, p&lt;0.001). Conclusion. Prevalence of asymptomatic malaria among children was found to be 2.6%. The study reported low sensitivity and PPV for PfHRP2 CareStart™ RDT in an asymptomatic population at instances of low parasitaemia. © 2019 Osman N. Kanwugu et al.The authors thank the head and entire staff of the Public Health Laboratory of the Tamale Teaching Hospital. .ey also extend their heartfelt appreciation to the staff of the two schools as well as to all parents of their study participants for allowing their wards to be enrolled onto the study