Surveillance strategies for the detection of new pathogen variants across epidemiological contexts.

Surveillance systems that monitor pathogen genome sequences are critical for rapidly detecting the introduction and emergence of pathogen variants. To evaluate how interactions between surveillance capacity, variant properties, and the epidemiological context influence the timeliness of pathogen variant detection, we developed a geographically explicit stochastic compartmental model to simulate the transmission of a novel SARS-CoV-2 variant in New York City. We measured the impact of (1) testing and sequencing volume, (2) geographic targeting of testing, (3) the timing and location of variant emergence, and (4) the relative variant transmissibility on detection speed and on the undetected disease burden.

Infectious disease surveillance needs for the United States: lessons from Covid-19.

The COVID-19 pandemic has highlighted the need to upgrade systems for infectious disease surveillance and forecasting and modeling of the spread of infection, both of which inform evidence-based public health guidance and policies. Here, we discuss requirements for an effective surveillance system to support decision making during a pandemic, drawing on the lessons of COVID-19 in the U.S.

Optimal environmental testing frequency for outbreak surveillance.

Public health surveillance for pathogens presents an optimization problem: we require enough sampling to identify intervention-triggering shifts in pathogen epidemiology, such as new introductions or sudden increases in prevalence, but not so much that costs due to surveillance itself outweigh those from pathogen-associated illness. To determine this optimal sampling frequency, we developed a general mathematical model for the introduction of a new pathogen that, once introduced, increases in prevalence exponentially. Given the relative cost of infection vs.

Spatiotemporal Trends in Group A Streptococcal Pharyngitis in the United States.

Background: Group A Streptococcus (GAS) causes an estimated 5.2 million outpatient visits for pharyngitis annually in the United States, with incidence peaking in winter, but the annual spatiotemporal pattern of GAS pharyngitis across the United States is poorly characterized.

Methods: We used outpatient claims data from individuals with private medical insurance between 2010 and 2018 to quantify GAS pharyngitis visit rates across U.

Clinical Risk and Outpatient Therapy Utilization for COVID-19 in the Medicare Population.

Importance: Multiple therapies are available for outpatient treatment of COVID-19 that are highly effective at preventing hospitalization and mortality. Although racial and socioeconomic disparities in use of these therapies have been documented, limited evidence exists on what factors explain differences in use and the potential public health relevance of these differences.

Objective: To assess COVID-19 outpatient treatment utilization in the Medicare population and simulate the potential outcome of allocating treatment according to patient risk for severe COVID-19.

Spatiotemporal Trends in Group A Streptococcal Pharyngitis in the United States.

Background: Group A (GAS) causes an estimated 5.2 million outpatient visits for pharyngitis annually in the United States (U.S.

Viral kinetics of sequential SARS-CoV-2 infections.

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we identified 71 individuals with two well-sampled SARS-CoV-2 infections between March 11, 2020, and July 28, 2022. We compared the SARS-CoV-2 viral kinetics of first vs.

Drug addiction unveils a repressive methylation ceiling in EZH2-mutant lymphoma.

Drug addiction, a phenomenon where cancer cells paradoxically depend on continuous drug treatment for survival, has uncovered cell signaling mechanisms and cancer codependencies. Here we discover mutations that confer drug addiction to inhibitors of the transcriptional repressor polycomb repressive complex 2 (PRC2) in diffuse large B-cell lymphoma. Drug addiction is mediated by hypermorphic mutations in the CXC domain of the catalytic subunit EZH2, which maintain H3K27me3 levels even in the presence of PRC2 inhibitors.

Quantifying the impact of immune history and variant on SARS-CoV-2 viral kinetics and infection rebound: A retrospective cohort study.

Background: The combined impact of immunity and SARS-CoV-2 variants on viral kinetics during infections has been unclear.

Methods: We characterized 1,280 infections from the National Basketball Association occupational health cohort identified between June 2020 and January 2022 using serial RT-qPCR testing. Logistic regression and semi-mechanistic viral RNA kinetics models were used to quantify the effect of age, variant, symptom status, infection history, vaccination status and antibody titer to the founder SARS-CoV-2 strain on the duration of potential infectiousness and overall viral kinetics.

Revealing contagion.

Mathematical models help predict and manage the course of pandemics.

Impact of Respiratory Infection and Chronic Comorbidities on Early Pediatric Antibiotic Dispensing in the United States.

Background: In the United States, children aged <5 years receive high volumes of antibiotics, which may contribute to antibiotic resistance. It has been unclear what role preventable illnesses and chronic comorbidities play in prompting antibiotic prescriptions.

Methods: We conducted an observational study with a cohort of 124 759 children aged <5 years born in the United States between 2008 and 2013 with private medical insurance.

Infectious disease dynamics and restrictions on social gathering size.

Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain size.

Infectious disease dynamics and restrictions on social gathering size.

Social gatherings can be an important locus of transmission for many pathogens including SARS-CoV-2. During an outbreak, restricting the size of these gatherings is one of several non-pharmaceutical interventions available to policy-makers to reduce transmission. Often these restrictions take the form of prohibitions on gatherings above a certain size.

Characterizing SARS-CoV-2 Viral Clearance Kinetics to Improve the Design of Antiviral Pharmacometric Studies.

A consensus methodology for the pharmacometric assessment of candidate SARS-CoV-2 antiviral drugs would be useful for comparing trial results and improving trial design. The time to viral clearance, assessed by serial qPCR of nasopharyngeal swab samples, has been the most widely reported measure of virological response in clinical trials, but it has not been compared formally with other metrics, notably model-based estimates of the rate of viral clearance. We analyzed prospectively gathered viral clearance profiles from 280 infection episodes in vaccinated and unvaccinated individuals.

Socioecology shapes child and adolescent time allocation in twelve hunter-gatherer and mixed-subsistence forager societies.

A key issue distinguishing prominent evolutionary models of human life history is whether prolonged childhood evolved to facilitate learning in a skill- and strength-intensive foraging niche requiring high levels of cooperation. Considering the diversity of environments humans inhabit, children's activities should also reflect local social and ecological opportunities and constraints. To better understand our species' developmental plasticity, the present paper compiled a time allocation dataset for children and adolescents from twelve hunter-gatherer and mixed-subsistence forager societies (n = 690; 3-18 years; 52% girls).

Analysis of multiple bacterial species and antibiotic classes reveals large variation in the association between seasonal antibiotic use and resistance.

Understanding how antibiotic use drives resistance is crucial for guiding effective strategies to limit the spread of resistance, but the use-resistance relationship across pathogens and antibiotics remains unclear. We applied sinusoidal models to evaluate the seasonal use-resistance relationship across 3 species (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and 5 antibiotic classes (penicillins, macrolides, quinolones, tetracyclines, and nitrofurans) in Boston, Massachusetts. Outpatient use of all 5 classes and resistance in inpatient and outpatient isolates in 9 of 15 species-antibiotic combinations showed statistically significant amplitudes of seasonality (false discovery rate (FDR) < 0.

Viral dynamics of acute SARS-CoV-2 infection and applications to diagnostic and public health strategies.

SARS-CoV-2 infections are characterized by viral proliferation and clearance phases and can be followed by low-level persistent viral RNA shedding. The dynamics of viral RNA concentration, particularly in the early stages of infection, can inform clinical measures and interventions such as test-based screening. We used prospective longitudinal quantitative reverse transcription PCR testing to measure the viral RNA trajectories for 68 individuals during the resumption of the 2019-2020 National Basketball Association season.

Modeling the impact of racial and ethnic disparities on COVID-19 epidemic dynamics.

Background: The impact of variable infection risk by race and ethnicity on the dynamics of SARS-CoV-2 spread is largely unknown.

Methods: Here, we fit structured compartmental models to seroprevalence data from New York State and analyze how herd immunity thresholds (HITs), final sizes, and epidemic risk change across groups.

Results: A simple model where interactions occur proportionally to contact rates reduced the HIT, but more realistic models of preferential mixing within groups increased the threshold toward the value observed in homogeneous populations.

Childhood Respiratory Outpatient Visits Correlate With Socioeconomic Status and Drive Geographic Patterns in Antibiotic Prescribing.

Background: Reducing geographic disparities in antibiotic prescribing is a central public health priority to combat antibiotic resistance, but drivers of this variation have been unclear.

Methods: We measured how variation in outpatient visit rates (observed disease) and antibiotic prescribing rates per visit (prescribing practices) contributed to geographic variation in per capita antibiotic prescribing in Massachusetts residents younger than 65 years between 2011 and 2015.

Results: Of the difference in per capita antibiotic prescribing between high- and low-prescribing census tracts in Massachusetts, 45.

Reduction in Antibiotic Prescribing Attainable With a Gonococcal Vaccine.

We estimated the fraction of antibiotic prescribing in the United States attributable to gonorrhea. Gonorrhea contributes to an outsized proportion of antibiotic prescriptions in young adults, males, and in the southern and western United States. A gonococcal vaccine could substantially reduce antibiotic prescribing in these populations.

Estimating SARS-CoV-2 seroprevalence and epidemiological parameters with uncertainty from serological surveys.

Establishing how many people have been infected by SARS-CoV-2 remains an urgent priority for controlling the COVID-19 pandemic. Serological tests that identify past infection can be used to estimate cumulative incidence, but the relative accuracy and robustness of various sampling strategies have been unclear. We developed a flexible framework that integrates uncertainty from test characteristics, sample size, and heterogeneity in seroprevalence across subpopulations to compare estimates from sampling schemes.

Model-informed COVID-19 vaccine prioritization strategies by age and serostatus.

Limited initial supply of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine raises the question of how to prioritize available doses. We used a mathematical model to compare five age-stratified prioritization strategies. A highly effective transmission-blocking vaccine prioritized to adults ages 20 to 49 years minimized cumulative incidence, but mortality and years of life lost were minimized in most scenarios when the vaccine was prioritized to adults greater than 60 years old.