Excellence in Diagnostic Science

Awarded publications 2025

Unified metagenomic method for rapid detection of microorganisms in clinical samples.
Commun Med (Lond). 2024;4(1):135. Alcolea-Medina A, Alder C, Snell LB et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/38972920/

Lower respiratory tract infections are a leading cause of sepsis-related deaths, yet current diagnostic methods struggle to identify all the pathogens responsible. Alcolea-Medina et al. present a metagenomic sequencing protocol that addresses this challenge by mechanically removing human DNA from clinical samples. Unlike existing methods, this technique can simultaneously detect DNA and RNA viruses, as well as bacteria – including atypical species that are difficult to culture – and fungi, all from a single specimen.

The protocol achieves a median 256-fold reduction in human genetic material, enabling efficient nanopore sequencing and producing automated reports within seven hours of processing the sample. When tested prospectively on samples from mechanically ventilated patients, the method demonstrated 90% sensitivity for bacterial detection and 92% for viral detection after just two hours of sequencing. In many cases, the approach also enabled the complete assembly of the genomes of the identified pathogens.

This comprehensive, pathogen-agnostic method provides a practical framework for incorporating metagenomic testing into standard clinical laboratories and has the potential to transform how clinicians diagnose and manage complex respiratory infections.

Health improvements by understanding residual risk in coronary artery disease and new targets for prevention/treatment: rationale and research protocol of the HURRICANE project.
Eur Heart J Open. 2025 Jan 28;5(1):oeaf005. Caselli C, Occhipinti M, Pane K et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/39949422/

Despite the best available medical treatments, patients with stable coronary artery disease are still at significant risk of disease progression and cardiovascular events. This residual risk is increasingly thought to be linked to a number of emerging factors, such as insulin resistance, atherogenic dyslipidaemia and chronic low-grade inflammation, which current therapies often fail to address adequately.

The HURRICANE project offers a comprehensive research framework designed to investigate the genetic and molecular profiles underlying these risk patterns, as well as their connection to more aggressive forms of coronary atherosclerosis. The study distinguishes itself through its use of advanced cardiac computed tomography to provide a detailed characterisation of atherosclerotic plaques, combined with multilayered molecular analyses, including genomics and lipidomics, in a well-defined patient population.

By integrating these multiple data sources, the researchers aim to develop and validate predictive models that go beyond traditional risk factors. The overarching objective is to map the complex biological networks that drive residual cardiovascular risk and potentially identify new molecular targets for more personalised and effective prevention strategies. These insights could ultimately help to reduce the ongoing clinical burden of coronary artery disease in patients who remain at risk despite receiving optimal current therapy.

Prevalence of chronic hepatitis C infection in the general population: results from a national survey, Estonia, July to December 2022.
Euro Surveill. 2024 Jul;29(30):2300651. Hleyhel M, Geller J, Sadou A et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/39056201/

In order to achieve the World Health Organization's target of eliminating viral hepatitis as a public health threat by 2030, it is necessary to have accurate, nationally representative data in order to track progress and guide interventions. This cross-sectional study addresses a significant knowledge gap by offering the first comprehensive national estimates of chronic hepatitis C virus (HCV) prevalence among Estonia's general adult population.

Conducted between July and December 2022, the study analysed anonymised residual blood samples from 4,217 individuals collected by general practitioners across all Estonian counties, ensuring geographic representativeness. Researchers used a rigorous testing algorithm combining enzyme-linked immunoassay, line-immunoblot assay and RT-qPCR to distinguish active infections from resolved cases.

The results revealed an overall chronic HCV prevalence of 0.8%, equating to around 8,100 individuals affected nationwide, with a total seroprevalence of 1.8%. While this overall rate is relatively low, the study identified important disparities within the population. Men and residents of Ida-Virumaa County had substantially higher infection rates, and the greatest burden of chronic infection was found in adults aged 40-49 – a pattern reflecting the region's primary transmission route of historical injecting drug use.

These detailed findings provide essential information for targeting screening and treatment programmes where they are most needed. Furthermore, the study's utilisation of existing laboratory infrastructure offers an efficient and cost-effective model that other countries can adopt to generate reliable prevalence data, monitor progress towards elimination, and evaluate the impact of direct-acting antiviral therapies.

Prognostic Value of a Multivariate Gut Microbiome Model for Progression from Normal Cognition to Mild Cognitive Impairment Within 4 Years.
Int J Mol Sci. 2025 May 15;26(10):4735. Bauch A, Baur J, Honold I et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/40429881/

Scientists have long suspected that gut bacteria influence brain health. However, it remained unclear whether microbes could predict cognitive decline before symptoms appeared. In a recent study, researchers followed a group of healthy adults for four years, tracking both their gut microbiome composition and mental function in order to identify early warning signs of mild cognitive impairment.

By metagenomic sequencing analysis of bacterial DNA from stool samples, the authors examined not only which species were present, but more importantly the biological functionality of the microbiome. While counting bacterial types showed limited predictive power, mapping their metabolic activities proved to be a remarkably accurate predictor of cognitive decline. A model based on these functional profiles correctly identified 84% of individuals who would subsequently experience cognitive decline, outperforming standard clinical assessments and simple bacterial counts.

The findings suggest that changes in gut microbial metabolism can occur years before noticeable memory loss. Such early detection could transform dementia prevention by enabling doctors to intervene before irreversible brain damage occurs. Simple stool tests could eventually replace expensive brain scans for screening high-risk patients.

Lipoprotein(a) concentrations and cardiovascular disease in patients with chronic kidney disease: Results from the German Chronic Kidney Disease study.
J Intern Med. 2024 Dec;296(6):510-526. Gruber I, Kollerits B, Forer L et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/39513193/

Chronic kidney disease (CKD) substantially increases the risk of cardiovascular disease, but the role of lipoprotein(a) (Lp(a)) – a genetically determined risk factor for cardiovascular disease – remains poorly understood in this patient group. Previous research has largely focused on end-stage renal disease, with limited investigation of mild-to-moderate CKD, and no studies have used genetic approaches to establish causality. This analysis from the prospective German Chronic Kidney Disease (GCKD) study addresses this issue by examining both measured and genetically predicted Lp(a) levels in over 5,000 patients with CKD stages 1–4.

Elevated Lp(a) levels were strongly associated with existing cardiovascular disease and new major adverse cardiovascular events during the 6.5-year follow-up period, with the risk increasing markedly at concentrations of 50 mg/dL or higher. A key strength of this study is its use of apo(a) isoform analysis and an Lp(a)-specific genetic risk score to estimate lifelong Lp(a) exposure, thereby reducing bias arising from temporary changes in kidney function. The Mendelian randomisation approach produced even stronger associations with cardiovascular outcomes, providing robust evidence that Lp(a) plays a causal role in cardiovascular disease among CKD patients.

The study also found that kidney impairment, particularly nephrotic-range albuminuria, substantially increased Lp(a) concentrations. However, genetically determined Lp(a) levels remained independent of measures of kidney function, suggesting that reduced kidney function increases Lp(a) rather than vice versa.

With Lp(a)-lowering therapies now in development, these findings highlight the need to include Lp(a) assessment in the evaluation of cardiovascular risk for patients with chronic kidney disease (CKD), a population that already faces elevated cardiovascular risk. This study provides robust genetic and epidemiological evidence that Lp(a) is a modifiable cardiovascular risk factor in individuals with chronic kidney disease.

HPV self-sampling in organized cervical cancer screening program: A randomized pilot study in Estonia in 2021.
J Med Screen. 2025 Mar;32(1):19-27. Hallik R, Innos K, Jänes J et al.

Link to full article: https://pubmed.ncbi.nlm.nih.gov/39091000/

Estonia has one of the highest rates of cervical cancer in Europe, partly due to inadequate participation in screening programmes. This randomised pilot study, embedded within the national organised screening programme, compared opt-in and opt-out strategies for offering HPV self-sampling to improve uptake.

A total of 55,693 women due for screening reminders were randomised into three groups: control, opt-in and opt-out. The opt-out approach, which involved sending self-sampling kits directly to participants, achieved the highest participation rate of 41.7%, which was significantly higher than in the opt-in group (34.1%) and the control group (29.0%). This benefit was particularly evident among older women (aged 60–65) and in certain geographical areas, demonstrating the strategy's effectiveness in engaging populations that are traditionally less involved in screening.

User feedback was overwhelmingly positive: 99% of participants found the self-sampling device easy to use, and 71.9% expressed a preference for this method for future screenings. Conducted during the pandemic, the study highlights the potential of self-sampling to maintain screening continuity during healthcare disruptions, a consideration that has prompted several countries to adopt self-collection options.

These population-level (or real world data) results provide strong evidence that incorporating HPV self-sampling, especially through an opt-out delivery model, can meaningfully increase screening participation. This approach is an important strategy for achieving the World Health Organization's cervical cancer elimination targets, particularly in settings where uptake of conventional screening remains insufficient.