Epstein-Barr virus and cytomegalovirus co-infections and mortality risk in patients with HIV-associated cryptococcal meningitis: a post-hoc analysis of a prospective nested cohort in the AMBITION-cm randomised controlled trial.

Background: HIV-associated cryptococcal meningitis case fatality remains greater than 25%. Co-prevalent infections might contribute to poor outcomes. We aimed to ascertain the prevalence and the clinical significance of Epstein-Barr virus (EBV) and cytomegalovirus co-infections in patients with cryptococcal meningitis to guide potential therapeutic interventions.

Correction: A pragmatic pipeline for drug resistance and lineage identification in Mycobacterium tuberculosis using whole genome sequencing.

[This corrects the article DOI: 10.1371/journal.pgph.

A pragmatic pipeline for drug resistance and lineage identification in Mycobacterium tuberculosis using whole genome sequencing.

Delays in accurate diagnosis of drug resistant tuberculosis (DR-TB) can hinder treatment. Whole genome sequencing (WGS) provides more information than standard molecular and phenotypic testing, but commonly used platforms are expensive to implement, and data interpretation requires significant expertise. We aimed to optimise a TB WGS diagnostic pipeline balancing user-friendliness, cost-effectiveness and time to results, whilst ensuring accuracy.

Computed Tomography of the Head Before Lumbar Puncture in Adults With Suspected Meningitis in High-HIV Prevalence Settings.

Background: The role of computed tomography (CT) before lumbar puncture (LP) is unclear, with limited evidence for a causal link between LP and cerebral herniation or for the ability of CT to identify individuals at risk of herniation. The risks of LP delay or deferral are potentially greater in high-HIV prevalence, resource-limited settings; we analyzed data from such a setting to determine the impact of CT on time to LP and treatment, as well as mortality.

Methods: Adults with suspected central nervous system (CNS) infection were enrolled prospectively into the Botswana National Meningitis Survey between 2016 and 2019.

Ex Vivo Host Transcriptomics During Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans Infection of Peripheral Blood Mononuclear Cells From South African Volunteers.

Cryptococcus neoformans, Cryptococcus gattii, and Candida albicans are opportunistic fungal pathogens associated with infections in immunocompromised hosts. Cryptococcal meningitis (CM) is the leading fungal cause of human immunodeficiency virus-related deaths globally, with the majority occurring in Africa. The human immune response to C albicans infection has been studied extensively in large genomics studies whereas cryptococcal infections, despite their severity, are comparatively understudied.

Gluten-Free Diet Induces Rapid Changes in Phenotype and Survival Properties of Gluten-Specific T Cells in Celiac Disease.

Background & Aims: The treatment of celiac disease (CeD) with gluten-free diet (GFD) normalizes gut inflammation and disease-specific antibodies. CeD patients have HLA-restricted, gluten-specific T cells persisting in the blood and gut even after decades of GFD, which are reactivated and disease driving upon gluten exposure. Our aim was to examine the transition of activated gluten-specific T cells into a pool of persisting memory T cells concurrent with normalization of clinically relevant biomarkers during the first year of treatment.

The diagnosis of central nervous system infections in resource-limited settings and the use of novel and molecular diagnostic platforms to improve diagnosis.

Introduction: Central nervous system infections (CNSI) disproportionately affect individuals in low-resource settings where diagnosis is challenging; large proportions of patients never receive a confirmed microbiological diagnosis resulting in inadequate management and high mortality. The epidemiology of CNSI varies globally and conventional diagnostics deployed in resource-limited settings have significant limitations, with an urgent need for improved diagnostic strategies.

Areas Covered: This review describes molecular platforms and other novel diagnostics used in the diagnosis of CNSI that are applicable to resource-limited settings.

Evaluation of Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry for Molecular Typing of Acinetobacter baumannii in Comparison with Orthogonal Methods.

Colonization and subsequent health care-associated infection (HCAI) with Acinetobacter baumannii are a concern for vulnerable patient groups within the hospital setting. Outbreaks involving multidrug-resistant strains are associated with increased patient morbidity and mortality and poorer overall outcomes. Reliable molecular typing methods can help to trace transmission routes and manage outbreaks.

Human Herpesvirus-6 Detection in Cerebrospinal Fluid on the BioFire FilmArray Meningitis/Encephalitis Panel in a High Human Immunodeficiency Virus-Prevalence African Setting.

The prevalence and clinical relevance of human herpesvirus-6 (HHV-6) detection in cerebrospinal fluid (CSF) using multiplex polymerase chain reaction (PCR) testing in patients with suspected meningoencephalitis in high human immunodeficiency virus-prevalence African settings are not known. We describe the clinical and laboratory characteristics of 13 patients with HHV-6 CSF PCR positivity in Botswana.

Whole-genome sequencing of isolates from persistently infected patients.

Background: Current understanding of the causes of treatment failure in is poor and antimicrobial susceptibility data are lacking. We used genome sequencing to seek evidence of antimicrobial resistance in isolates sourced from patients who were persistently infected.

Methods: Genomic DNA was extracted from isolates cultured in McCoy cell monolayers.

An inter-laboratory study to investigate the impact of the bioinformatics component on microbiome analysis using mock communities.

Despite the advent of whole genome metagenomics, targeted approaches (such as 16S rRNA gene amplicon sequencing) continue to be valuable for determining the microbial composition of samples. Amplicon microbiome sequencing can be performed on clinical samples from a normally sterile site to determine the aetiology of an infection (usually single pathogen identification) or samples from more complex niches such as human mucosa or environmental samples where multiple microorganisms need to be identified. The methodologies are frequently applied to determine both presence of micro-organisms and their quantity or relative abundance.

Genome-Wide Association Study Identifies Novel Colony Stimulating Factor 1 Locus Conferring Susceptibility to Cryptococcosis in Human Immunodeficiency Virus-Infected South Africans.

Background: is the most common cause of meningitis in human immunodeficiency virus (HIV)-infected Africans. Despite universal exposure, only 5%-10% of patients with HIV/acquired immune deficiency syndrome and profound CD4 T-cell depletion develop disseminated cryptococcosis: host genetic factors may play a role. Prior targeted immunogenetic studies in cryptococcosis have comprised few Africans.

The role of IS in the covid-19 pandemic: A liquid-modern perspective.

History shows that pandemics can catalyse enormous change, fundamentally transforming the way people make sense of the world. Technologies can also be catalysts of change. While digital technologies are playing a vital role in tackling the covid-19 pandemic, the pandemic also presents a significant opportunity for digital technologies.

Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results.

Cross-transmission Is Not the Source of New Mycobacterium abscessus Infections in a Multicenter Cohort of Cystic Fibrosis Patients.

Background: Mycobacterium abscessus is an extensively drug-resistant pathogen that causes pulmonary disease, particularly in cystic fibrosis (CF) patients. Identifying direct patient-to-patient transmission of M. abscessus is critically important in directing an infection control policy for the management of risk in CF patients.

1,4-dihydroxy quininib attenuates growth of colorectal cancer cells and xenografts and regulates the TIE-2 signaling pathway in patient tumours.

Colorectal cancer (CRC) is the second leading cause of cancer associated deaths in developed countries. Cancer progression and metastatic spread is reliant on new blood vasculature, or angiogenesis. Tumour-related angiogenesis is regulated by pro- and anti-angiogenic factors secreted from malignant tissue in a stepwise process.

Correction to: Whole genome sequencing Mycobacterium tuberculosis directly from sputum identifies more genetic diversity than sequencing from culture.

He authors reported that one of the authors' names was typeset incorrectly in the authorship list.

Intraoperative and major postoperative complications and survival of dogs undergoing surgical management of epiglottic retroversion: 50 dogs (2003-2017).

Objective: To report intraoperative and major postoperative complications in dogs treated surgically for epiglottic retroversion (ER), compare the incidence of major postoperative complications between procedures, and report survival of surgically treated dogs.

Study Design: Multi-institutional retrospective study.

Sample Population: Fifty dogs treated with 78 procedures.

Whole genome sequencing Mycobacterium tuberculosis directly from sputum identifies more genetic diversity than sequencing from culture.

Background: Repeated culture reduces within-sample Mycobacterium tuberculosis genetic diversity due to selection of clones suited to growth in culture and/or random loss of lineages, but it is not known to what extent omitting the culture step altogether alters genetic diversity. We compared M. tuberculosis whole genome sequences generated from 33 paired clinical samples using two methods.

Children With Cystic Fibrosis Are Infected With Multiple Subpopulations of Mycobacterium abscessus With Different Antimicrobial Resistance Profiles.

Background: Children with cystic fibrosis (CF) can develop life-threatening infections of Mycobacterium abscessus. These present a significant clinical challenge, particularly when the strains involved are resistant to antibiotics. Recent evidence of within-patient subclones of M.

Microbial Translocation Does Not Drive Immune Activation in Ugandan Children Infected With HIV.

Objective: Immune activation is associated with morbidity and mortality during human immunodeficiency virus (HIV) infection, despite receipt of antiretroviral therapy (ART). We investigated whether microbial translocation drives immune activation in HIV-infected Ugandan children.

Methods: Nineteen markers of immune activation and inflammation were measured over 96 weeks in HIV-infected Ugandan children in the CHAPAS-3 Trial and HIV-uninfected age-matched controls.

Direct Whole-Genome Sequencing of Sputum Accurately Identifies Drug-Resistant Mycobacterium tuberculosis Faster than MGIT Culture Sequencing.

The current methods available to diagnose antimicrobial-resistant infections require a positive culture or only test a limited number of resistance-associated mutations. A rapid accurate identification of antimicrobial resistance enables the prompt initiation of effective treatment. Here, we determine the utility of whole-genome sequencing (WGS) of directly from routinely obtained diagnostic sputum samples to provide a comprehensive resistance profile compared to that from mycobacterial growth indicator tube (MGIT) WGS.