Biomedical subjects

Stephanie W Lo

Publications and source records attributed to Stephanie W Lo.

3 recordsLinked to original sources

PubMed2026

Pneumococcal population structure influences the effects of air pollution on invasive disease risk in South Africa.

Streptococcus pneumoniae is highly diverse, comprising over 100 serotypes and hundreds of genomic lineages amid widespread vaccination. While it can cause invasive pneumococcal disease (IPD) which exhibits pronounced seasonal spikes, the interplay between pneumococcal diversity and environmental drivers remains unexplored. Here we analysed 59,017 IPD cases over 19 years from South Africa, incorporating 4,350 genome-sequenced isolates, using Bayesian spatiotemporal models to link environmental exposure and pneumococcal diversity. Cumulatively, across an 8-week period, moderate relative humidity (33-49%) and cold minimum temperatures (4-10 °C) increased IPD risk by 5% and 4%, respectively. Conversely, warm maximum temperatures (27-38 °C) were associated with up to a 10% increased risk within a week of exposure. There was a positive association between air pollution (PM2.5) and IPD, although it varied by age, disease presentation, and most notably serotype and lineage. Specifically, the lag time between PM2.5 exposure and disease onset varied by serotype, with only serotypes 4, 8 and 23F conferring an immediate IPD risk. High prevalence of GPSC21 lineage (serotype 19F) also modified the pollution response, shifting the lag structure to produce immediate risk of disease following high PM2.5 exposure. Our results demonstrate that pneumococcal population structure shapes air quality risk which in turn can shape the fitness landscape of microbial populations. Integration of these data may inform public health policy.

Journal Article↗

PubMed2026

A reusable model of pangenome selection informs optimal surveillance strategies over vaccine introductions.

BACKGROUND: The human pathogen Streptococcus pneumoniae is a major cause of disease, including pneumonia and meningitis. The introduction of Pneumococcal Conjugate Vaccines (PCVs) initially reduced the burden of disease through a reduction of colonisation by vaccine-targeted serotypes. However, since PCVs only target a proportion of pneumococcal serotypes, they shift intraspecific competition, eventually allowing non-targeted types to 'replace' vaccine types. Understanding the host and pathogen factors causing replacement is important for future vaccine development. Mechanistic understanding of vaccine replacement dynamics is crucial for forecasting and optimisation of genomic surveillance strategies to evaluate realised vaccine effectiveness. METHODS: We developed a mathematical model of the genomic and demographic factors which explain vaccine replacement, used this model to replicate serotype-frequency changes, and investigated cost-effective genomic surveillance strategies. We extended a forward-time model based on the Wright-Fisher model, developing a user-friendly model framework that describes the post-vaccine dynamics of S. pneumoniae populations. Our model describes vaccine replacement as a function of vaccine impact, immigration of new strains, and negative frequency-dependent selection (NFDS) on the accessory genome content. RESULTS: We used our model to study vaccine replacement in newly sequenced genomic surveillance data from Kathmandu (Nepal), and existing data from Massachusetts (US) and Southampton (UK), with distinct surveillance strategies. We showed that the model with NFDS better replicates replacement dynamics than a null model without NFDS, and that NFDS likely only acts on part of the S. pneumoniae accessory genome. We found consistent estimates for vaccination effectiveness across the different study locations and region-specific genes under NFDS, highlighting the importance of conducting genomic surveillance in each country of interest. By simulating data from the model, we showed that an optimal surveillance strategy prioritises per-sampling sample size over sampling frequency for small sampling budgets. CONCLUSIONS: Our model can be used to predict vaccine replacement dynamics after PCV introduction, and can be easily reapplied to analyse new data from vaccine introductions or new regions. Our model is available in the R package Stubentiger (Studying Balancing Evolution (NFDS) To Investigate Genome Replacement) on GitHub https://github.com/bacpop/Stubentiger .

Streptococcus pneumoniae↗

PubMed2026

Five decades of pneumococcal meningitis in Spain: a single-centre, clinical and genomic, retrospective, observational study.

BACKGROUND: Pneumococcal meningitis remains a major threat, with high fatality rates and long-term sequelae, despite advances in vaccination and treatment. We aimed to examine the associations between pneumococcal serotypes, Global Pneumococcal Sequence Cluster (GPSC), antimicrobial resistance, source of infection, and clinical outcomes in adults with pneumococcal meningitis. METHODS: In this single-centre, clinical and genomic, retrospective, observational study, we analysed all laboratory-confirmed cases of adult pneumococcal meningitis recorded at Hospital Universitari de Bellvitge, Spain. Clinical data were obtained from a prospectively maintained clinical database and linked to microbiological and genomic data by unique patient identifiers. Clinical sources of infection were classified as cerebrospinal fluid leakage, acute otitis media, or haematogenous origin. Disease severity was defined as shock at presentation, sequelae as any persistent neurological deficit at discharge, and mortality as death within 30 days. Serotype data were available for 265 isolates, and whole-genome sequencing was done on 200 viable isolates. For outcome analyses, patients who did not receive dexamethasone were excluded. Serotype, GPSCs, antimicrobial susceptibility, phylogenetic, and genome-wide association study (GWAS) data were analysed to assess determinants of meningitis source, disease severity, sequelae, and 30-day mortality. FINDINGS: 387 adult patients (median age 58 years [IQR 45-68]; 54% male) with pneumococcal meningitis were recorded between Jan 1, 1974, and Dec 31, 2023. Acute otitis media was the most frequent source of pneumococcal meningitis (174 [45%] of 387 cases) and was mainly caused by serotype 3 (pneumococcal conjugate vaccine [PCV]13; GPSC12). The 30-day case-fatality rate in this group was 17 (10%) of 174 (95% CI 5·8-15·2). Haematogenous episodes accounted for 104 (27%) of 387 cases and had a significantly higher 30-day case-fatality rate (50 [48%] of 104; 95% CI 38·2-58·1; p<0·0001) with a higher frequency of serotype 4. Cerebrospinal fluid leakage accounted for 105 (27%) of 387 cases and had the lowest 30-day case-fatality rate (nine [9%] of 105; 95% CI 4·0-15·6) and broader serotype diversity. The introduction of PCV7 and PCV13 resulted in declines in vaccine-targeted serotypes and β-lactam resistance. Whole-genome sequencing identified 60 distinct GPSCs. Among prevalent lineages, GPSC16 (20 [10%] of 200; serotypes 19A and 23F) and GPSC6 (18 [9%] of 200; serotypes 9V, 11A, and 14) were associated with β-lactam resistance. GWAS did not identify genetic variants significantly associated with severity, sequelae, or mortality. INTERPRETATION: This longitudinal study provides a comprehensive view of adult pneumococcal meningitis over five decades, revealing changes in sources of infection, serotype distribution, pneumococcal lineages, and antimicrobial resistance patterns over time. Lineage-level findings suggested variability in clinical outcomes, underscoring the importance of continued genomic surveillance and supporting consideration of broader vaccine targets. GPSC12 predominance and its association with mortality and more severe outcomes highlight the need for preventive measures against serotype 3, although these findings require confirmation in larger multicentre cohorts. FUNDING: Instituto de Salud Carlos III, cofunded by European Social Fund, and the Centro de Investigación Biomédica en Red de Enfermedades Respiratorias, and the Centro de Investigación Biomédica en Red de Enfermedades Infecciosas, both at the Instituto de Salud Carlos III.

Journal Article↗