Assessment of sewer connectivity in the United States and its implications for equity in wastewater-based epidemiology.

Wastewater-based epidemiology is a promising public health tool that can yield a more representative view of the population than case reporting. However, only about 80% of the U.S. population is connected to public sewers, and the characteristics of populations missed by wastewater-based epidemiology are unclear. To address this gap, we used publicly available datasets to assess sewer connectivity in the U.S. by location, demographic groups, and economic groups. Data from the U.S. Census' American Housing Survey revealed that sewer connectivity was lower than average when the head of household was American Indian and Alaskan Native, White, non-Hispanic, older, and for larger households and those with higher income, but smaller geographic scales revealed local variations from this national connectivity pattern. For example, data from the U.S. Environmental Protection Agency showed that sewer connectivity was positively correlated with income in Minnesota, Florida, and California. Data from the U.S. Census' American Community Survey and Environmental Protection Agency also revealed geographic areas with low sewer connectivity, such as Alaska, the Navajo Nation, Minnesota, Michigan, and Florida. However, with the exception of the U.S. Census data, there were inconsistencies across datasets. Using mathematical modeling to assess the impact of wastewater sampling inequities on inferences about epidemic trajectory at a local scale, we found that in some situations, even weak connections between communities may allow wastewater monitoring in one community to serve as a reliable proxy for an interacting community with no wastewater monitoring, when cases are widespread. A systematic, rigorous assessment of sewer connectivity will be important for ensuring an equitable and informed implementation of wastewater-based epidemiology as a public health monitoring system.

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. Design, Setting, and Participants: This cross-sectional study included patients enrolled in Medicare in 2022 across the US, identified with 100% Medicare fee-for-service claims. Main Outcomes and Measures: The primary outcome was any COVID-19 outpatient therapy utilization. Secondary outcomes included COVID-19 testing, ambulatory visits, and hospitalization. Differences in outcomes were estimated based on patient demographics, treatment contraindications, and a composite risk score for mortality after COVID-19 based on demographics and comorbidities. A simulation of reallocating COVID-19 treatment, particularly with nirmatrelvir, to those at high risk of severe disease was performed, and the potential COVID-19 hospitalizations and mortality outcomes were assessed. Results: In 2022, 6.0% of 20 026 910 beneficiaries received outpatient COVID-19 treatment, 40.5% of which had no associated COVID-19 diagnosis within 10 days. Patients with higher risk for severe disease received less outpatient treatment, such as 6.4% of those aged 65 to 69 years compared with 4.9% of those 90 years and older (adjusted odds ratio [aOR], 0.64 [95% CI, 0.62-0.65]) and 6.4% of White patients compared with 3.0% of Black patients (aOR, 0.56 [95% CI, 0.54-0.58]). In the highest COVID-19 severity risk quintile, 2.6% were hospitalized for COVID-19 and 4.9% received outpatient treatment, compared with 0.2% and 7.5% in the lowest quintile. These patterns were similar among patients with a documented COVID-19 diagnosis, those with no claims for vaccination, and patients who are insured with Medicare Advantage. Differences were not explained by variable COVID-19 testing, ambulatory visits, or treatment contraindications. Reallocation of 2022 outpatient COVID-19 treatment, particularly with nirmatrelvir, based on risk for severe COVID-19 would have averted 16 503 COVID-19 deaths (16.3%) in the sample. Conclusion: In this cross-sectional study, outpatient COVID-19 treatment was disproportionately accessed by beneficiaries at lower risk for severe infection, undermining its potential public health benefit. Undertreatment was not driven by lack of clinical access or treatment contraindications.

Estimating the fitness cost and benefit of antimicrobial resistance from pathogen genomic data.

Increasing levels of antibiotic resistance in many bacterial pathogen populations are a major threat to public health. Resistance to an antibiotic provides a fitness benefit when the bacteria are exposed to this antibiotic, but resistance also often comes at a cost to the resistant pathogen relative to susceptible counterparts. We lack a good understanding of these benefits and costs of resistance for many bacterial pathogens and antibiotics, but estimating them could lead to better use of antibiotics in a way that reduces or prevents the spread of resistance. Here, we propose a new model for the joint epidemiology of susceptible and resistant variants, which includes explicit parameters for the cost and benefit of resistance. We show how Bayesian inference can be performed under this model using phylogenetic data from susceptible and resistant lineages and that by combining data from both we are able to disentangle and estimate the resistance cost and benefit parameters separately. We applied our inferential methodology to several simulated datasets to demonstrate good scalability and accuracy. We analysed a dataset of Neisseria gonorrhoeae genomes collected between 2000 and 2013 in the USA. We found that two unrelated lineages resistant to fluoroquinolones shared similar epidemic dynamics and resistance parameters. Fluoroquinolones were abandoned for the treatment of gonorrhoea due to increasing levels of resistance, but our results suggest that they could be used to treat a minority of around 10% of cases without causing resistance to grow again.

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. Across all models, the burden of infection fell disproportionately on minority populations: in a model fit to Long Island serosurvey and census data, 81% of Hispanics or Latinos were infected when the HIT was reached compared to 34% of non-Hispanic whites. Conclusions: Our findings, which are meant to be illustrative and not best estimates, demonstrate how racial and ethnic disparities can impact epidemic trajectories and result in unequal distributions of SARS-CoV-2 infection. Funding: K.C.M. was supported by National Science Foundation GRFP grant DGE1745303. Y.H.G. and M.L. were funded by the Morris-Singer Foundation. M.L. was supported by SeroNet cooperative agreement U01 CA261277.

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, 45.2% was attributable to variation in outpatient visit rates, while 25.8% was explained by prescribing practices. Outpatient visits for sinusitis, pharyngitis, and suppurative otitis media accounted for 30.3% of the gap in prescribing, with most of the variation in visit rates concentrated in children younger than 10 years. Outpatient visits for these conditions were less frequent in census tracts with high social deprivation index. CONCLUSIONS: Interventions aimed at reducing geographic disparities in antibiotic prescribing should target the drivers of outpatient visits for respiratory illness and should account for possible underutilization of health services in areas with the lowest antibiotic consumption. Our findings challenge the conventional wisdom that prescribing practices are the main driver of geographic disparities in antibiotic use.

Reductions in commuting mobility correlate with geographic differences in SARS-CoV-2 prevalence in New York City.

SARS-CoV-2-related mortality and hospitalizations differ substantially between New York City neighborhoods. Mitigation efforts require knowing the extent to which these disparities reflect differences in prevalence and understanding the associated drivers. Here, we report the prevalence of SARS-CoV-2 in New York City boroughs inferred using tests administered to 1,746 pregnant women hospitalized for delivery between March 22nd and May 3rd, 2020. We also assess the relationship between prevalence and commuting-style movements into and out of each borough. Prevalence ranged from 11.3% (95% credible interval [8.9%, 13.9%]) in Manhattan to 26.0% (15.3%, 38.9%) in South Queens, with an estimated city-wide prevalence of 15.6% (13.9%, 17.4%). Prevalence was lowest in boroughs with the greatest reductions in morning movements out of and evening movements into the borough (Pearson R = -0.88 [-0.52, -0.99]). Widespread testing is needed to further specify disparities in prevalence and assess the risk of future outbreaks.

Individual quarantine versus active monitoring of contacts for the mitigation of COVID-19: a modelling study.

BACKGROUND: Voluntary individual quarantine and voluntary active monitoring of contacts are core disease control strategies for emerging infectious diseases such as COVID-19. Given the impact of quarantine on resources and individual liberty, it is vital to assess under what conditions individual quarantine can more effectively control COVID-19 than active monitoring. As an epidemic grows, it is also important to consider when these interventions are no longer feasible and broader mitigation measures must be implemented. METHODS: To estimate the comparative efficacy of individual quarantine and active monitoring of contacts to control severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), we fit a stochastic branching model to reported parameters for the dynamics of the disease. Specifically, we fit a model to the incubation period distribution (mean 5·2 days) and to two estimates of the serial interval distribution: a shorter one with a mean serial interval of 4·8 days and a longer one with a mean of 7·5 days. To assess variable resource settings, we considered two feasibility settings: a high-feasibility setting with 90% of contacts traced, a half-day average delay in tracing and symptom recognition, and 90% effective isolation; and a low-feasibility setting with 50% of contacts traced, a 2-day average delay, and 50% effective isolation. FINDINGS: Model fitting by sequential Monte Carlo resulted in a mean time of infectiousness onset before symptom onset of 0·77 days (95% CI -1·98 to 0·29) for the shorter serial interval, and for the longer serial interval it resulted in a mean time of infectiousness onset after symptom onset of 0·51 days (95% CI -0·77 to 1·50). Individual quarantine in high-feasibility settings, where at least 75% of infected contacts are individually quarantined, contains an outbreak of SARS-CoV-2 with a short serial interval (4·8 days) 84% of the time. However, in settings where the outbreak continues to grow (eg, low-feasibility settings), so too will the burden of the number of contacts traced for active monitoring or quarantine, particularly uninfected contacts (who never develop symptoms). When resources are prioritised for scalable interventions such as physical distancing, we show active monitoring or individual quarantine of high-risk contacts can contribute synergistically to mitigation efforts. Even under the shorter serial interval, if physical distancing reduces the reproductive number to 1·25, active monitoring of 50% of contacts can result in overall outbreak control (ie, effective reproductive number <1). INTERPRETATION: Our model highlights the urgent need for more data on the serial interval and the extent of presymptomatic transmission to make data-driven policy decisions regarding the cost-benefit comparisons of individual quarantine versus active monitoring of contacts. To the extent that these interventions can be implemented, they can help mitigate the spread of SARS-CoV-2. FUNDING: National Institute of General Medical Sciences, National Institutes of Health.

The distribution of antibiotic use and its association with antibiotic resistance.

Antibiotic use is a primary driver of antibiotic resistance. However, antibiotic use can be distributed in different ways in a population, and the association between the distribution of use and antibiotic resistance has not been explored. Here, we tested the hypothesis that repeated use of antibiotics has a stronger association with population-wide antibiotic resistance than broadly-distributed, low-intensity use. First, we characterized the distribution of outpatient antibiotic use across US states, finding that antibiotic use is uneven and that repeated use of antibiotics makes up a minority of antibiotic use. Second, we compared antibiotic use with resistance for 72 pathogen-antibiotic combinations across states. Finally, having partitioned total use into extensive and intensive margins, we found that intense use had a weaker association with resistance than extensive use. If the use-resistance relationship is causal, these results suggest that reducing total use and selection intensity will require reducing broadly distributed, low-intensity use.

Racial/Ethnic Disparities in Antimicrobial Drug Use, United States, 2014-2015.

Using a US nationwide survey, we measured disparities in antimicrobial drug acquisition by race/ethnicity for 2014-2015. White persons reported twice as many antimicrobial drug prescription fills per capita as persons of other race/ethnicities. Characterizing antimicrobial drug use by demographic might improve antimicrobial drug stewardship and help address antimicrobial drug resistance.

Trends in outpatient antibiotic use and prescribing practice among US older adults, 2011-15: observational study.

OBJECTIVE: To identify temporal trends in outpatient antibiotic use and antibiotic prescribing practice among older adults in a high income country. DESIGN: Observational study using United States Medicare administrative claims in 2011-15. SETTING: Medicare, a US national healthcare program for which 98% of older adults are eligible. PARTICIPANTS: 4.5 million fee-for-service Medicare beneficiaries aged 65 years old and older. MAIN OUTCOME MEASUREMENTS: Overall rates of antibiotic prescription claims, rates of potentially appropriate and inappropriate prescribing, rates for each of the most frequently prescribed antibiotics, and rates of antibiotic claims associated with specific diagnoses. Trends in antibiotic use were estimated by multivariable regression adjusting for beneficiaries' demographic and clinical covariates. RESULTS: The number of antibiotic claims fell from 1364.7 to 1309.3 claims per 1000 beneficiaries per year in 2011-14 (adjusted reduction of 2.1% (95% confidence interval 2.0% to 2.2%)), but then rose to 1364.3 claims per 1000 beneficiaries per year in 2015 (adjusted reduction of 0.20% over 2011-15 (0.09% to 0.30%)). Potentially inappropriate antibiotic claims fell from 552.7 to 522.1 per 1000 beneficiaries over 2011-14, an adjusted reduction of 3.9% (3.7% to 4.1%). Individual antibiotics had heterogeneous changes in use. For example, azithromycin claims per beneficiary decreased by 18.5% (18.2% to 18.8%) while levofloxacin claims increased by 27.7% (27.2% to 28.3%). Azithromycin use associated with each of the potentially appropriate and inappropriate respiratory diagnoses decreased, while levofloxacin use associated with each of those diagnoses increased. CONCLUSION: Among US Medicare beneficiaries, overall antibiotic use and potentially inappropriate use in 2011-15 remained steady or fell modestly, but individual drugs had divergent changes in use. Trends in drug use across indications were stronger than trends in use for individual indications, suggesting that guidelines and concerns about antibiotic resistance were not major drivers of change in antibiotic use.

Secular trends in Helicobacter pylori seroprevalence in adults in the United States: evidence for sustained race/ethnic disparities.

Helicobacter pylori seroprevalence levels in US adults participating in the continuous National Health and Nutrition Examination Survey (1999-2000) increased with age in all racial/ethnic groups, with significantly higher age-standardized levels in Mexican Americans (64.0%, 95% confidence interval (CI): 58.8, 69.2) and non-Hispanic blacks (52.0%, 95% CI: 48.3, 55.7) compared with non-Hispanic whites (21.2%, 95% CI: 19.1, 23.2). Although seroprevalence levels remained similar to those found in National Health and Nutrition Examination Surveys from 1988 to 1991 among non-Hispanic blacks and Mexican Americans, they were significantly lower in non-Hispanic whites, especially at older ages. The factors driving the decline in H. pylori seroprevalence appear to be acting preferentially on the non-Hispanic white population.