Biomedical subjects

Nathan D Grubaugh

Publications and source records attributed to Nathan D Grubaugh.

5 recordsLinked to original sources

PubMed2026

Genomic surveillance of a deeply sampled local population reveals age-specific drivers of RSV transmission.

Respiratory syncytial virus (RSV) disproportionately causes severe infections among infants and older adults, yet the key age group responsible for viral spread to other age groups remains poorly defined. While current immunization approaches effectively reduce disease severity among the most vulnerable, identifying the core drivers of infection is essential to effectively disrupt population-level transmission. By generating 910 whole-genome viral sequences of RSV from all age groups (<1 to 65+ years) in Connecticut, we identified that children aged 12-35 months are the primary drivers of viral transmission to other age groups. This group significantly shapes the genetic diversity of circulating strains. Furthermore, we found that RSV is introduced into the community through frequent and independent entries from other US regions throughout the year, rather than through a single explosive seasonal introduction or long-term local persistence. Ultimately, our findings justify prevention strategies that expand beyond reducing disease burden to actively prioritizing the reduction of transmission and infection.

Journal Article↗

PubMed2026

Frequent introductions and climate suitability drive increasing dengue risk in Florida.

In recent years, detection of local dengue cases in Florida have increased in both frequency and geographical extent. From 2022 to 2024, consecutive outbreaks in Miami-Dade County were mainly caused by a single lineage of dengue virus (DENV) serotype 3, prompting questions about changing epidemiology and a transition towards endemicity. In this study, we used mathematical modeling and genomic epidemiology to reveal the spatiotemporal dynamics and drivers of local dengue cases in Florida. We found that annual clusters and outbreaks were caused by frequent short-lived DENV introductions, primarily from the Caribbean, and did not find evidence for local trans-seasonal DENV lineage persistence. Further, we show that the climate-driven increases in local suitability for Aedes aegypti transmission and travel-associated cases were the greatest risk factors for outbreaks in Miami-Dade and the geographic expansion of dengue in Florida. Overall, while we do not yet find evidence for endemicity, we demonstrate how climatic trends are enhancing the local public health risk caused by dengue in Florida.

Journal Article↗

PubMed2026

Evolutionary history of Jamestown Canyon virus reveals complex multi-vector ecology.

Jamestown Canyon virus (JCV) is a historically understudied mosquito-borne virus of increasing concern in North America. We generated 658 whole-genome JCV sequences from northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997 to 2022. Then, we applied phylodynamic methods to demonstrate how mosquito phenology structures the maintenance and evolution of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s, and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of ∼3 × 10-5 substitutions per site per year (s/s/y), making it one of the slowest-evolving known RNA viruses, because the virus spends ∼10 months per year in evolutionary stasis while overwintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of ∼30-60 km2/year, which is more similar to slow-moving tick-borne viruses than to other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contributed to periodic bursts of spatial diffusion and amplification within seasons. We demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework for rapidly advancing our evolutionary and ecological knowledge of understudied viruses.

Animals↗

PubMed2026

A tiled amplicon protocol for culture-free whole-genome sequencing of M. tuberculosis from clinical specimens.

Whole-genome sequencing of Mycobacterium tuberculosis can be a valuable tool for TB surveillance and treatment, providing insights into transmission patterns and comprehensive drug susceptibility testing. However, the slow growth of M. tuberculosis means traditional culture-based sequencing methods can take weeks to return results, which has limited the widespread adoption of these techniques and limited their use in clinical decision-making. Tiled amplicon sequencing is a fast, reliable, and cost-effective method of whole-genome sequencing that can be done directly on clinical specimens and has been implemented at scale in academic and public health laboratories across the world; it was the cornerstone of SARS-CoV-2 sequencing and has been adapted for a wide range of viral pathogens. However, similar methods are not yet available for far larger bacterial genomes. Extending this approach to M. tuberculosis would significantly reduce the cost, labor, and turnaround time for whole-genome sequencing. We designed a tiled amplicon panel consisting of 5,128 primers that covers the entire M. tuberculosis genome, the largest tiled amplicon sequencing panel we are aware of to date. Applying our amplicon panels to clinical samples of sputum, we show the ability to recover whole-genome bacterial sequences without the need for culture. The resulting sequence data can be used to determine M. tuberculosis lineage and reliably identify markers of drug resistance. Using this approach in clinical settings could reduce the time needed for comprehensive drug susceptibility testing from weeks to days and enable genomic epidemiology to be performed at scale, even in resource-limited settings.IMPORTANCEWe have developed and tested an amplicon panel, TB-seq, for the priority pathogen Mycobacterium tuberculosis, demonstrating recovery of near-full genomes directly from patient sputum, including mixed and low-concentration samples. This approach significantly reduces the turnaround time for this slow-growing bacterium while maintaining high accuracy in detecting clinically relevant mutations, including those associated with drug resistance. Given the global burden of tuberculosis and the critical need for faster diagnostic solutions, we believe our method has the potential to improve clinical decision-making and public health strategies.

Mycobacterium tuberculosis↗

PubMed2026

Genomic epidemiology of dengue virus 2 and 3 reveals repeated introductions and exportations of several lineages in Colombia.

Dengue fever, a major mosquito-borne viral disease, is transmitted by Aedes mosquitoes and poses a significant global health burden. Despite extensive research, the spatiotemporal dynamics of dengue virus (DENV) lineages in Colombia remain understudied. Here, we analyze 11,443 complete genome sequences from Colombia and the Americas to map the genomic epidemiology of DENV-2 and DENV-3. Phylogeographic reconstruction revealed multiple independent introductions and exportations of the DENV-2 II and III lineages, as well as the DENV-3 lineage III_C.2, underscoring Colombia's critical role as both a source and a sink of viral traffic within the Americas. Antigenic profiling demonstrated distinct clustering of emergent lineages in antigenic space, consistent with immune-escape-driven turnover. These results highlight the necessity of sustained, high-resolution genomic surveillance to guide targeted public health interventions and mitigate dengue transmission across the region.

Dengue Virus↗