Science

In the three years since Omicron emergence, SARS-CoV-2 dynamics have exhibited persistent twice-yearly waves in the United States, peaking in late summer and winter, with heterogeneity in timing and intensity across states. This semiannual pattern sharply contrasts with typical annual respiratory pathogen dynamics in the US, yet their underlying mechanisms and whether this pattern will persist remain poorly understood. Here, we tested several hypothesized mechanisms and found that a combination ...

Pathogenic organisms are typically thought to be constrained by a tradeoff between the rate and duration of transmission, an assumption that underpins a considerable body of evolutionary theory. Here we test for a transmission-duration tradeoff using detailed historical malaria infection data from an era prior to widespread use of antibiotics when humans were deliberately infected with malaria parasites as treatment for neurosyphilis (malariatherapy). These time series follow individual human in...

Programmatic decisions regarding surveillance and intervention for trachoma are made at the district level, reflecting an implicit assumption that transmission within districts is sufficiently homogeneous. However, as trachoma transmission declines, residual pockets of transmission may become spatially heterogeneous at sub-district scales. Using cluster-level data from 12 districts in Amhara, Ethiopia (2019-2023), we assess the spatial structure of Pgp3 antibody responses, a sensitive measure of...

The two largest US measles outbreaks in over two decades (2025 Gaines County, Texas: 414 cases, contained; 2025-2026 Spartanburg County, South Carolina: 923+ cases, ongoing) occurred in counties with similar sub-threshold K-12 MMR coverage (85.1% vs 88.8%), yet their trajectories diverged dramatically. Using kernel density estimation with a common bandwidth and bootstrap uncertainty quantification, we compared sub-county vaccination data at the district level for Texas (3 districts, 3,560 studen...

BackgroundStrikingly low allocation of SARS-CoV-2 vaccine to the African Continent limits its capacity to control transmission. Characterizing the trajectory of vaccination efforts and their impact on the expected burden of SARS-CoV-2 will help planning vaccine delivery strategies, and public health interventions more broadly. As the burden is strongly age-dependent, this requires an understanding of the age-structured dynamics of susceptible individuals, accounting for the combined effects of v...

Ambient air pollution has been associated with increased incidence of chronic disease and is estimated to contribute towards 4.2 million early deaths annually. Whilst the health impacts are well described, less is understood about the underlying biological mechanisms, particularly when considering the co-occurrence of multiple pollutants. Using an atmospheric chemistry transportation model (EMEP4UK), we generate pre-baseline sampling pollution exposure estimates for eight pollutants in Generatio...

Household transmission of EV-D68 was identified in 35 of 1040 households (3.4%) in the Pacific Northwest between 2022-2024, with an estimated secondary attack rate of 15%. Sequences from within households clustered closely with 0 to 2 pairwise nucleotide differences (median 1) between cases 6-14 days apart (median 7).

Biological fitness quantifies the efficiency and selective advantage of pathogens and hosts in their bilateral interaction. Key questions--such as how much more infectious an emerging variant is compared with its predecessor, or how much protection vaccination offers relative to no vaccination--require fitness to be measured systematically, in real time, and ideally beyond controlled laboratory settings. We propose an approach that infers biological fitness from mostly non-biological data on inf...

Epigenetic clocks estimate biological age from DNA methylation patterns at CpG sites, providing robust predictions of mortality and morbidity risk. "Blue zones"--regions of exceptional longevity--offer a unique opportunity to investigate how biological aging diverges from chronological age. However, standard clocks are typically trained on large, heterogeneous datasets, reflecting average population trends rather than region-specific dynamics. Using data from the Costa Rican Longevity and Health...

An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...

Background: Human-to-human transmission of pathogens fundamentally depends on interactions among infectious and susceptible individuals, yet traditional population-scale models often overlook the stochastic, behaviour-driven, and highly heterogeneous nature of these interactions. Methods: Here, we develop a large-scale actor-based model capturing early epidemic dynamics of a novel respiratory pathogen on dynamic contact networks. We build these networks upon explicitly integrating detailed demog...

Infection with pnuemococcus bacteria is generally mild but can be more severe in the young and elderly, causing invasive pneumococcal disease (IPD) and community-acquired pneumonia (CAP). Although paediatric pneumococcal conjugate vaccine (PCV) programmes and elderly pneumococcal polysaccharide vaccine (PPV) programmes have reduced cases, we estimate that pneumococcal infection still leads to direct health care costs of around {pound}68M and approximately 16 thousand QALY losses in England per y...

Dengue is one of the worlds highest-burden arboviral diseases. Although classically considered an urban disease, many regions experience a substantial dengue burden in rural areas. The combined influence of long-term climate, short-term weather variation, local built environments, and land-use gradients on dengue dynamics in rural settings remains poorly understood, limiting our ability to predict shifting risk under global change. Here, we investigate these dynamics in Costa Rica to disentangle...

Measles outbreaks have surged globally in recent years, but current surveillance systems have limited capacity to monitor measles virus (MeV) transmission and evolution at population scale. Although MeV can be detected in wastewater, the public health potential of wastewater genomic surveillance for MeV remains largely unexplored. Here, we deploy sensitive, low-cost MeV wastewater genomic surveillance combining virus concentration, whole-genome amplicon sequencing, and bioinformatic analysis alo...

The prospective design of vaccine efficacy trials for deployment in outbreaks requires advance consideration of plausible outbreak scenarios, anticipated vaccine characteristics, and logistical and ethical constraints. As part of CEPIs 100 Days Mission to accelerate vaccine development against a novel Disease X, we evaluated trial designs for a hypothetical Nipah-X outbreak. We assumed Nipah-X would share key features with Nipah, including high case fatality rates and substantial super-spreading...

Biological ageing begins before birth, with early-life exposures shaping late-life health. These exposures drive health inequities early, yet specific exposures and the composition of the ageing exposome remain largely undefined. This gap may persist as the field lacks agnostic investigations accounting for non-linearity, interactions and subtle signals. We aimed to identify exposures predictive of epigenetic ageing accumulated during childhood and adolescence and explore the composition of the...

BackgroundVaccines can prevent severe disease by preventing infection or by reducing progression among those who become infected. Vaccine effectiveness against progression given infection is often used to quantify this second mechanism, but it conditions on infection, which is itself affected by vaccination. As a result, this estimand lacks a clear causal interpretation and may behave non-intuitively over time. MethodsWe introduce a conceptual framework that models protection against infection ...

Dengue virus (DENV), comprising four distinct serotypes (DENV-1 to DENV-4), poses a major public health challenge in tropical regions. Infection with one serotype confers long-term immunity to that serotype alone, while subsequent heterologous infections are associated with increased risk of severe disease, necessitating vaccines that induce durable, balanced immunity across all serotypes. However, achieving such balance immunity remains a central challenge for dengue vaccine development. Using ...

Genomic surveillance of influenza viruses informs vaccine strain selection and evolutionary forecasting. Sequencing efforts vary widely across U.S. states, which raises concerns about spatial sampling bias. We evaluated how well 10,958 influenza virus genomes sampled by our group in Michigan captured the genetic diversity in 34,743 genomes circulating nationally from the 2021/22 through 2024/25 seasons. We defined seasonal hemagglutinin haplotypes and tracked their detection across states. A sma...

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting a...