Biomedical subjects

Vitali Sintchenko

Publications and source records attributed to Vitali Sintchenko.

4 recordsLinked to original sources

PubMed2026

The public health utility of whole genome sequencing: Insights from a tuberculosis outbreak in Australia and perspectives of public health professionals.

Whole Genome Sequencing (WGS) is increasingly being used to enhance tuberculosis (TB) surveillance and management. However, evidence on how WGS shapes real-world decision-making remains limited. This study explored the utility of WGS in the context of a TB outbreak in Victoria, Australia. We conducted a case study to (1) describe a TB outbreak in Victoria using epidemiological and genomic data and (2) explore the perceived benefits and limitations of WGS through qualitative interviews with laboratory and public health professionals involved in the investigation. The interviews were analysed thematically. From 2017 - 2023, 36 people were linked to a large lineage 4 TB outbreak comprising 3 sub-clusters. WGS connected two patients who were initially not epidemiologically linked to the outbreak, prompting additional contact screening at a medical clinic. From interviews with 10 laboratory and public health professionals, WGS was considered a useful tool, although there was a gap between its potential and realised utility. WGS strengthened confidence in suspected transmission links, which was particularly valuable when epidemiological evidence was sparce or uncertain. This was relevant in this investigation where TB stigma, a prolonged timeframe, and cross-jurisdictional transmission were challenges. Barriers to public health action from WGS included long turnaround times, difficulties drawing conclusions from identical isolates, and uncertainties around public health follow-up actions. This case study demonstrates that WGS can inform meaningful public health action, while also identifying opportunities to improve its utility. WGS for public health should involve real-time sequencing along with steps to support the translation of findings into actions such as action-focused WGS training, mechanisms to support consistent follow-up, and improved record-keeping systems.

Journal Article↗

PubMed2026

Genome-sequencing-based benchmarking of antimicrobial resistance, treatment outcomes and healthcare transmission events for Clostridioides difficile infection in Australian hospitals.

BACKGROUND: Clostridioides difficile infection (CDI) remains a priority for infection prevention and control in health care, particularly with the emergence of hypervirulent strains and antimicrobial resistance (AMR). AIM: To characterize the genomic epidemiology and AMR profiles of culture-confirmed CDI cases within tertiary hospitals in Australia. METHODS: A total of 155 C. difficile isolates from 142 patients with CDI diagnosed in four hospitals between 2023 and 2025 were studied. Data collected included patient demographics, severity of infection, antibiotic treatment and clinical outcomes at 8 weeks. Phenotypic susceptibility to vancomycin, fidaxomicin, metronidazole, moxifloxacin, meropenem, tetracycline and rifaximin were determined by agar dilution. Isolates underwent whole-genome sequencing (WGS) for genotyping and resistome assessment. FINDINGS: WGS differentiated 39 distinct sequence types among CDI isolates across different healthcare services. In total, 100 isolates were singletons and 55 (35% clustering rate) isolates were considered to be genomically related (difference of two or fewer single-nucleotide polymorphisms). Of these, 12 patients (8.5%) with close hospital contact formed six epidemiologically linked clusters. Phenotypic susceptibility results were obtained for 134 (86.4%) CDI isolates. There was no phenotypic resistance to vancomycin [minimum inhibitory concentration required to inhibit the growth of 90% of isolates (MIC90) 1 mg/L], metronidazole (MIC90 0.5 mg/L) or fidaxomicin (MIC90 0.5 mg/L). There was no association in the study cohort between the presence of resistance genes or reduced phenotypic susceptibility and CDI recurrence. CONCLUSION: Genomic analysis of C. difficile isolates did not identify any outbreaks or an association between the sequence type or presence of a resistance gene and clinical outcomes. High-resolution characterization and identification of antibiotic resistance, CDI clinical relapse and recent transmission offered by genome sequencing can provide important benchmarks for hospital infection control.

Antibiotic resistance↗

PubMed2026

Characterisation of Bordetella pertussis virulence and macrolide resistance in Australia by targeted culture-independent sequencing: a genomic epidemiology study.

BACKGROUND: Bordetella pertussis continues to circulate globally despite widespread vaccination, with a notable epidemic in 2024. Its resurgence is confounded by the emergence of pertactin-deficient, macrolide-resistant B pertussis strains in Asia and Europe, which are under-recognised by conventional diagnostics. We aimed to apply targeted culture-independent next-generation sequencing (tNGS) of respiratory specimens to improve global B pertussis diagnostic capability and genomic surveillance. METHODS: We did a nationwide genomic epidemiology study of B pertussis RT-PCR-positive respiratory specimens that were retrospectively and prospectively collected by diagnostic and public health laboratories in six of seven states and territories of Australia. Specimens underwent tNGS and macrolide-resistant B pertussis-specific PCR, and an opportunistic subset from New South Wales and Queensland were cultured for confirmatory susceptibility testing and whole-genome sequencing. Sequencing data were analysed for genome recovery, virulence profiles, and macrolide resistance mutations, and were compared with international macrolide-resistant B pertussis genomes and ancestral Australian genomes. The performance of the tNGS approach was assessed with logistic regression relative to RT-PCR cycle threshold values, and sensitivity and specificity values were calculated. FINDINGS: 255 respiratory specimens positive for B pertussis were included in the study. 64 (25%) were retrospectively collected between Jan 12, 2012, and Dec 31, 2023, and 191 (75%) were prospectively collected between Jan 1 and Oct 28, 2024. Of these 255 specimens, 148 (58%) yielded near-complete B pertussis genomes through tNGS. Seven co-circulating lineages of B pertussis were documented, including two associated with macrolide-resistance. Eight epidemiologically unrelated and geographically dispersed cases of macrolide-resistant B pertussis with a 23S rRNA 2037A→G mutation were identified by tNGS and confirmed by whole-genome sequencing. Three of these were further validated by phenotypic testing. The estimated prevalence of macrolide resistance among Australian cases positive for B pertussis was 4% (eight of 188). INTERPRETATION: tNGS can recover near-complete B pertussis genomes directly from clinical specimens, enabling identification of macrolide resistance mutations and high-resolution phylogenetic analysis. These findings show that tNGS complements PCR-based surveillance by providing genome-wide assessment of resistance, virulence, and genomic diversity in a single workflow. FUNDING: NSW Health Prevention Research Support Program.

Macrolides↗

PubMed2025

Multi-scale phylodynamic modelling of rapid punctuated pathogen evolution.

Computational multi-scale pandemic modelling remains a major and timely challenge. Here we identify specific requirements for a new class of models simulating pandemics across three scales: (1) pathogen evolution, often punctuated by the rapid emergence of new variants, (2) human interactions within a heterogeneous population, and (3) public health responses which constrain individual actions to control the disease transmission. We then present a pandemic modelling framework satisfying these requirements and capable of simulating feedback loops between dynamics unfolding at these different scales. The developed framework comprises a stochastic agent-based model of pandemic spread, coupled with a phylodynamic model that incorporates within-host pathogen evolution. It is validated with a case study, modelling the punctuated evolution of SARS-CoV-2, based on global and contemporary genomic surveillance data, which captures a large heterogeneous population. We demonstrate that the model replicates the essential features of the COVID-19 pandemic and virus evolution, while retaining computational tractability and scalability.

SARS-CoV-2↗