Ecological and evolutionary mechanisms driving within-patient emergence of antimicrobial resistance

The ecological and evolutionary mechanisms of antimicrobial resistance (AMR) emergence within patients and how these vary across bacterial infections are poorly understood. Increasingly widespread use of pathogen genome sequencing in the clinic enables a deeper understanding of these processes. In this Review, we explore the clinical evidence to support four major mechanisms of within-patient AMR emergence in bacteria: spontaneous resistance mutations; in situ horizontal gene transfer of resistance genes; selection of pre-existing resistance; and immigration of resistant lineages. Within-patient AMR emergence occurs across a wide range of host niches and bacterial species, but the importance of each mechanism varies between bacterial species and infection sites within the body. We identify potential drivers of such differences and discuss how ecological and evolutionary analysis could be embedded within clinical trials of antimicrobials, which are powerful but underused tools for understanding why these mechanisms vary between pathogens, infections and individuals. Ultimately, improving understanding of how host niche, bacterial species and antibiotic mode of action combine to govern the ecological and evolutionary mechanism of AMR emergence in patients will enable more predictive and personalized diagnosis and antimicrobial therapies

Functional immune responses against SARS-CoV-2 variants of concern after fourth COVID-19 vaccine dose or infection in patients with blood cancer

Summary Patients with blood cancer continue to have a greater risk of inadequate immune responses following three COVID-19 vaccine doses and risk of severe COVID-19 disease. In the context of the CAPTURE study (NCT03226886) we report immune responses in 80 patients with blood cancer who received a fourth dose of BNT162b2. We measured neutralising antibody titres (NAbT) using a live virus microneutralization assay against wild-type (WT), Delta, Omicron BA.1 and BA.2 and T cell responses against WT and Omicron BA.1 using an activation-induced marker (AIM) assay. The proportion of patients with detectable NAb titres and T cell responses after the fourth vaccine dose increases compared to those after the third vaccine dose. Patients who received B cell-depleting therapies within 12 months before vaccination have the greatest risk of not having detectable NAbT. In addition, we report immune responses in 57 patients with breakthrough infections after vaccination

Sustainable intensification – “oxymoron” or “third-way”? A systematic review

Sustainable Intensification (SI) is a term that has been advanced to capture a concept that some consider as the ‘third paradigm’ for global agricultural development. However, the term has become subject to intense debates as well as scepticism and confusion regarding its meaning and the characteristics of production systems that could indicate SI (defined as “indicators”). This has resulted in a proliferation of literature. We have conducted a systematic review of a sample of this literature analysing the most commonly suggested indicators of SI in order to investigate the extent to which the critiques of SI are valid in their viewpoints that SI is an oxymoron, underpinned by a productivist agenda, and to identify the critical issues in the development of a comprehensive and unambiguous set of SI indicators. From 633 articles identified by a search of relevant databases, a sample of 75 articles were selected and analysed using the NVIVO™ software. The results were organised according to a Socio-Ecological Systems (SES) framework comprising seven sub-systems or components − resource system, resource units, governance system, resource users, interactions, outcomes, and environment. A total of 218 indicators (both positive and negative) were identified. Most of these indicators focused on the ‘outcomes’ of agricultural systems with the majority being related to agricultural production. Few indicators were identified as relating to the economic and societal dimensions of food systems. Whilst this potentially suggested a productivist bias in the current interpretation of SI it was difficult to draw a black and white conclusion, since for the other system components, the majority of the indicators suggested appeared to take a more holistic point-of-view and emphasised both productivity and sustainability of agricultural systems. Our analysis suggests that a key reason why SI may be viewed with scepticism is a lack of specificity and elucidation of the rationale, scale, and farm type for which SI is proposed. Moreover, a number of the indicators were so loosely defined that the interventions they imply could be enacted without due consideration of the social impacts of their adoption. We conclude that there is need to develop SI indicators according to specific farming types and scales and also with more consideration of the social and political dimensions of food systems in order to promote a constructive dialogue around the concept of SI to take place. Unless the concept of SI is described and measured in such a holistic and inclusive manner, it is unlikely to be accepted as a valid descriptor of sought-after agricultural practices by players in the Third Sector

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

A prevalence survey of patients with indwelling urinary catheters on district nursing caseloads in the United Kingdom: The Community Urinary Catheter Management (CCaMa) Study

Background: Catheter-associated urinary tract infection (CAUTI) is common in both hospitals and the community. Aim: To investigate the prevalence of indwelling urinary catheters on district nursing caseloads in the UK. Methods: Participants were recruited through the Infection Prevention Society (IPS). An electronic survey was undertaken on a single day between November 2017 and January 2018. Data were analysed using descriptive statistics. Findings: A total of 49,575 patients were included in the survey, of whom 5352 had an indwelling urinary catheter. This gave a point prevalence of 10.8% (95% confidence interval [CI] = 10.53–11.07), which varied between organisations, ranging from 2.36% (95% CI = 2.05–2.73) to 22.02% (95% CI = 20.12–24.05). Of catheters, 5% were newly placed (within four weeks). Of these, most (77%) had a documented indication for insertion. Only half of patients with a newly placed catheter had a plan for its removal. This varied between organisations in the range of 20%–96%. Only 13% of patients had a patient-held management plan or ‘catheter passport’ but these patients were significantly more likely to also have an active removal plan (28/36 [78%] vs. 106/231 [46%]; P &lt; 0.0001). Alternative bladder management strategies had been considered for 70/267 (26%) patients. Discussion: The management of patients with an indwelling urinary catheter represents a significant component of district nursing caseloads. Given the high proportion of newly catheterised patients without an active management plan for removal of the catheter, the establishment of an optimal management pathway should be the focus of future prevention efforts.</p

ОСНОВАНИЯ КЛАССИФИКАЦИИ ГЕОГРАФИЧЕСКИХ ГРАНИЦ: ОНТОЛОГИЯ ГЕОГРАФИИ И КУЛЬТУРНОГО РАЗНООБРАЗИЯ

Понятие границ представляет собой один из основных философских вопросов, возникающих и необходимых при осмыслении географии с гео-онтологической точки зрения, и ее актуальность для современных дискуссий подчеркивалась и изу-чалась различными авторами. Но какого рода объектами являются географические границы? Какого вида границы были определены современными онтологами гео-графии? Как границы могут быть классифицированы c гео-онтологической точки зрения? Каковы основные современные классификации географических границ? Как культура и человеческие убеждения могут влиять на такие классификации? Эти вопросы представляют собой отправную точку в данной работе, направленной на рассмотрение того, как понятие границ определяется современными онтологами географии, как были выявлены и классифицированы виды географических границ, а также влияние культурных различий и человеческих убеждений на такие гео-онтологические классификации. Во-первых, мы будем опираться на таксономии Б. Смита и Э. Гальтона, которые предлагают наиболее цитируемые комплексные классификации географических границ, охватывающие физические, биологические, психологические, социальные и политические явления. Во-вторых, мы будем обсу-ждать важность культурных различий и человеческих убеждений для гео-онтологической классификации, исходя из соображений Б. Смита и Д.М. Марка