Publications by authors named "Nathan D Grubaugh"

Dengue fever, a major mosquito-borne viral disease, is transmitted by 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.

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Wolbachia is a promising strategy to inhibit dengue virus (DENV) transmission by Ae. aegypti mosquitoes. Laboratory studies assessing DENV inhibition by Wolbachia typically have not considered natural frequent mosquito blood feeding behavior.

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Dengue, caused by dengue virus (DENV) 1-4, remains a global public health concern, with Brazil experiencing some of the largest epidemics. The re-emergence of DENV-3 in Brazil between 2023 and 2024 has raised concerns about new outbreaks due to the absence of sustained circulation of this serotype in recent years. This study investigates the dynamics of DENV-3 in Brazil, focusing on the spread of the 3III_B.

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As new vaccines are being developed for fast-evolving viruses, determining when and how to update them, and what data should inform these decisions, remains a significant challenge. We developed a model to inform these vaccine updates in near real-time and applied it to SARS-CoV-2 by quantifying the relationship between vaccine effectiveness (VE) and genetic distance from mRNA vaccine formulation sequences using 10,156 genomes from Connecticut (April 2021-July 2024) and data from over one million controls, employing a two-stage statistical approach. We showed a strong inverse correlation between spike gene amino acid distance and VE; every 10 amino acid substitutions away from the vaccine sequences resulted in a 15.

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Arthropod-borne viruses (arboviruses) impose substantial global health and economic burdens, affecting both human and animal populations. These viruses - including dengue, chikungunya, Rift Valley fever, Crimean-Congo haemorrhagic fever and bluetongue viruses - have complex transmission cycles involving vertebrate hosts and arthropod vectors. Their circulation in livestock and wildlife complicate surveillance, as traditional epidemiological approaches rely mainly on human clinical data.

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The COVID-19 pandemic has been marked by continuous emergence of novel SARS-CoV-2 variants. Questions remain about the mechanisms with which those variants establish themselves in new geographic areas. We performed a discrete phylogeographic analysis on 18,529 sequences of the SARS-CoV-2 Omicron BA.

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Background: Cross-reactive immune memory responses to orthopoxviruses in humans remain poorly characterised despite their relevance for vaccine design and outbreak control. We aimed to assess the magnitude, specificity, and durability of cross-reactive immune responses elicited by smallpox vaccines and mpox virus infection.

Methods: We did a multicohort observational study involving participants from the USA, Brazil, and Portugal across four groups: Dryvax (first-generation smallpox vaccine) recipients vaccinated 40-80 years ago, JYNNEOS (third-generation smallpox vaccine) recipients vaccinated within the past year, a cohort receiving both vaccines, and patients infected with clade IIb mpox.

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We used a detailed dengue classification to assess the variability in disease severity and outcomes in a cohort of patients classified as "dengue with warning signs" according to the 2009 World Health Organization (WHO) criteria. We describe a wide range of severity and outcomes, which highlights the need and potential to improve the current WHO dengue classification.

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Dengue virus (DENV) is a mosquito-borne virus that poses a continued and increasing threat to public health. A promising strategy to mitigate the burden of DENV is introgression of the virus-inhibiting bacterium into populations in the field. While previous studies on -mediated virus inhibition have typically assessed viral replication following a single bloodmeal, the main vector of DENV, , feeds frequently, often biting multiple hosts per gonotrophic cycle and promptly attempting to refeed following egg laying.

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Pathogen sequencing is an important tool for disease surveillance and demonstrated its high value during the COVID-19 pandemic. Viral sequencing during the pandemic allowed us to track disease spread, quickly identify new variants, and guide the development of vaccines. Tiled amplicon sequencing, in which a panel of primers is used for multiplex amplification of fragments across an entire genome, was the cornerstone of SARS-CoV-2 sequencing.

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Powassan virus (POWV) is an emerging tick-borne virus that causes severe meningoencephalitis in the United States, Canada, and Russia. Serology is generally the preferred diagnostic modality, but PCR on cerebrospinal fluid, blood, or urine has an important role, particularly in immunocompromised patients who are unable to mount a serologic response. Although the perceived poor sensitivity of PCR in the general population may be due to the biology of infection and health-seeking behavior (with short viremic periods that end before hospital presentation), limitations in assay design may also contribute.

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Article Synopsis
  • - Dengue cases reached an all-time high in 2023-2024, particularly in Valle del Cauca, Colombia.
  • - The study identified all four serotypes of the dengue virus and various lineages, indicating a diverse viral presence during the outbreak.
  • - Researchers believe that environmental factors, especially climatic conditions, played a significant role in the surge of dengue cases in Colombia.
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Article Synopsis
  • Researchers studied 9,902 SARS-CoV-2 infections over two years to understand how genetic variations in the virus and factors like host age and vaccination status affect viral copies.
  • They used a genome-wide association study (GWAS) to find specific genetic changes (SNPs) in the virus correlated with higher or lower viral copies, particularly noting interactions between these SNPs.
  • The study revealed that SNPs linked to higher viral loads were mainly seen in Delta and Omicron variants, while those linked to lower loads were found in Omicron BA.1, suggesting the potential for GWAS to analyze other pathogens and their variants.
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Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system.

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Background: Dengue fever remains a significant public health challenge in tropical and subtropical regions, with its transmission dynamics being influenced by both environmental factors and human mobility. The Dominican Republic, a biodiversity hotspot in the Caribbean, has experienced recurrent dengue outbreaks, yet detailed understanding of the virus's transmission pathways and the impact of climatic factors remains limited. This study aims to elucidate the recent transmission dynamics of the dengue virus (DENV) in the Dominican Republic, utilizing a combination of genomic sequencing and epidemiological data analysis, alongside an examination of historical climate patterns.

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Circulating bat coronaviruses represent a pandemic threat. However, our understanding of bat coronavirus pathogenesis and transmission potential is limited by the lack of phenotypically characterized strains. We created molecular clones for the two closest known relatives of SARS-CoV-2, BANAL-52 and BANAL-236.

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Article Synopsis
  • Global dengue cases hit record highs in 2023-24, with significant outbreaks seen in Valle del Cauca, Colombia.
  • Researchers found all four dengue virus serotypes and various lineages present in the area during the outbreak.
  • The study indicates that factors beyond just the virus types, such as climate conditions, might be contributing to the surge in cases.
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Omicron surged as a variant of concern in late 2021. Several distinct Omicron variants appeared and overtook each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (R).

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Dengue virus (DENV) is currently causing epidemics of unprecedented scope in endemic settings and expanding to new geographical areas. It is therefore critical to track this virus using genomic surveillance. However, the complex patterns of viral genomic diversity make it challenging to use the existing genotype classification system.

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Background: The increasing burden of dengue virus on public health due to more explosive and frequent outbreaks highlights the need for improved surveillance and control. Genomic surveillance of dengue virus not only provides important insights into the emergence and spread of genetically diverse serotypes and genotypes, but it is also critical to monitor the effectiveness of newly implemented control strategies. Here, we present DengueSeq, an amplicon sequencing protocol, which enables whole-genome sequencing of all four dengue virus serotypes.

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Dengue is the most prevalent mosquito-borne viral disease in humans, and cases are continuing to rise globally. In particular, islands in the Caribbean have experienced more frequent outbreaks, and all four dengue virus (DENV) serotypes have been reported in the region, leading to hyperendemicity and increased rates of severe disease. However, there is significant variability regarding virus surveillance and reporting between islands, making it difficult to obtain an accurate understanding of the epidemiological patterns in the Caribbean.

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SARS-CoV-2 antibody levels may serve as a correlate for immunity and could inform optimal booster timing. The relationship between antibody levels and protection from infection was evaluated in vaccinated individuals from the US National Basketball Association who had antibody levels measured at a single time point from September 12, 2021, to December 31, 2021. Cox proportional hazards models were used to estimate the risk of infection within 90 days of serologic testing by antibody level (<250, 250-800, and >800 AU/mL ), adjusting for age, time since last vaccine dose, and history of SARS-CoV-2 infection.

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Article Synopsis
  • We use a mix of genomics and epidemiology to study recent dengue virus spread in the Dominican Republic, highlighting a new north-south transmission route with multiple virus strains co-existing.
  • Our analysis of historical climate data shows that rising temperatures may increase the likelihood of dengue transmission over time.
  • These insights can help public health agencies develop targeted interventions and better prepare for the dengue risks associated with climate change.
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