Biomedical subjects

Kathryn E Holt

Publications and source records attributed to Kathryn E Holt.

3 recordsLinked to original sources

PubMed2026

Strengthening the Reporting of Observational Studies in Epidemiology Enhanced Prevalence and Incidence Criteria (STROBE EPIC): An Extension of the STROBE Statement.

Prevalence and incidence are fundamental metrics with numerous applications in epidemiology. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guideline lacks specific items for reporting studies of disease prevalence or incidence. To address this gap, the STROBE Enhanced Prevalence and Incidence Criteria (STROBE EPIC) extension was developed in accordance with established methods for reporting guideline development. The authors generated an initial list of reporting items, conducted a modified Delphi process, and convened a face-to-face consensus meeting to confirm the need for a STROBE extension and to generate an early version of the checklist. They conducted 2 further Delphi surveys, first extending from typhoid and other invasive salmonelloses to all infectious diseases, and then to noncommunicable diseases and injuries. Finally, experts piloted the checklist on relevant manuscripts to critically assess if it was clear, concise, complete, and free of errors. An executive group curated the checklist after every survey round. The STROBE EPIC checklist comprises 47 items in the domains of title (1 item), abstract (2 items), introduction (1 item), methods (25 items), results (6 items), discussion (7 items), and other information (5 items). STROBE EPIC items address reporting of study design, adjustment factors for underreporting and underdiagnosis, denominator population estimation, case ascertainment methods, factors producing artefactual changes to observed disease prevalence or incidence, limitations of incomplete surveillance coverage, generalizability of short-duration studies, and data availability. The authors anticipate that the STROBE EPIC extension will be used by researchers, authors, modelers, burden-of-disease researchers, peer reviewers, and journal editors to optimize the presentation of epidemiologic evidence to support diverse health policy decisions.

Humans↗

PubMed2025

A metabolic atlas of the Klebsiella pneumoniae species complex reveals lineage-specific metabolism and capacity for intra-species co-operation.

The Klebsiella pneumoniae species complex inhabits a wide variety of hosts and environments, and is a major cause of antimicrobial resistant infections. Genomics has revealed the population comprises multiple species/sub-species and hundreds of distinct co-circulating sub-lineage (SLs) that are associated with distinct gene complements. A substantial fraction of the pan-genome is predicted to be involved in metabolic functions and hence these data are consistent with metabolic differentiation at the SL level. However, this has so far remained unsubstantiated because in the past it was not possible to explore metabolic variation at scale. Here, we used a combination of comparative genomics and high-throughput genome-scale metabolic modeling to systematically explore metabolic diversity across the K. pneumoniae species complex (n = 7,835 genomes). We simulated growth outcomes for each isolate using carbon, nitrogen, phosphorus, and sulfur sources under aerobic and anaerobic conditions (n = 1,278 conditions per isolate). We showed that the distributions of metabolic genes and growth capabilities are structured in the population, and confirmed that SLs exhibit unique metabolic profiles. In vitro co-culture experiments demonstrated reciprocal commensalistic cross-feeding between SLs, effectively extending the range of conditions supporting individual growth. We propose that these substrate specializations may promote the existence and persistence of co-circulating SLs by reducing nutrient competition and facilitating commensal interactions. Our findings have implications for understanding the eco-evolutionary dynamics of K. pneumoniae and for the design of novel strategies to prevent opportunistic infections caused by this World Health Organization priority antimicrobial resistant pathogen.

Klebsiella pneumoniae↗

PubMed2025

Determining genotype and antimicrobial resistance of Salmonella Typhi in environmental samples by amplicon sequencing.

BACKGROUND: Estimates of the burden of typhoid fever due to Salmonella enterica serovar Typhi (S. Typhi) rely on data from clinical surveillance, which is rarely done in low income settings and is also limited by the poor sensitivity of the assays used and the reliance on health seeking by patients. Environmental surveillance for S. Typhi shed by symptomatic and asymptomatic individuals in wastewater offers a sensitive surveillance tool that could help to inform burden estimates. Sequencing S. Typhi direct from wastewater concentrates has the potential to identify circulating genotypes and associated antimicrobial resistance (AMR) genes, supporting public health interventions such as vaccination and antimicrobial usage. METHODOLOGY AND PRINCIPAL FINDINGS: We designed a multiplex targeted amplicon sequencing protocol for genotyping and determining AMR in S. Typhi from wastewater samples, targeting SNPs that identify genotypes of interest and both chromosomal and plasmid-borne AMR. PCR products were sequenced using the Oxford Nanopore Technologies (ONT) MinION, and genotypes and AMR identified using the GenoTyphi program. We tested this approach on samples from south India from both hospital outflow and wastewater collected from the community. All samples tested were suspected to be positive for S. Typhi following quantitative PCR for ttr, tviB, and staG gene targets. Out of 110 samples tested we were able to determine a genotype and/or AMR for 8. All samples that gave a genotype call suggested a genotype consistent with those found in clinical cases in India during the same time period and produced consensus sequences that clustered with S. Typhi when included in a phylogenetic tree. CONCLUSIONS: In this study, we provide proof of concept data for amplicon sequencing of S. Typhi in wastewater which with further optimisation could be used to complement clinical surveillance data or provide data on S. Typhi presence in the absence of clinical surveillance. This information can inform public health interventions, and the concept could be applied to other pathogens of interest for genotyping from environmental surveillance samples.

Salmonella typhi↗