Clade I-Associated Mpox Cases Associated with Sexual Contact, the Democratic Republic of the Congo.

We report a cluster of clade I monkeypox virus infections linked to sexual contact in the Democratic Republic of the Congo. Case investigations resulted in 5 reverse transcription PCR-confirmed infections; genome sequencing suggest they belonged to the same transmission chain. This finding demonstrates that mpox transmission through sexual contact extends beyond clade IIb.

Selection Bias Requires Selection: The Case of Collider Stratification Bias.

In epidemiology, collider stratification bias, the bias resulting from conditioning on a common effect of two causes, is oftentimes considered a type of selection bias, regardless of the conditioning methods employed. In this commentary, we distinguish between two types of collider stratification bias: collider restriction bias due to restricting to one level of a collider (or a descendant of a collider) and collider adjustment bias through inclusion of a collider (or a descendant of a collider) in a regression model. We argue that categorizing collider adjustment bias as a form of selection bias may lead to semantic confusion, as adjustment for a collider in a regression model does not involve selecting a sample for analysis. Instead, we propose that collider adjustment bias can be better viewed as a type of overadjustment bias. We further provide two distinct causal diagram structures to distinguish collider restriction bias and collider adjustment bias. We hope that such a terminological distinction can facilitate easier and clearer communication.

COVID-19 annual update: a narrative review.

Three and a half years after the pandemic outbreak, now that WHO has formally declared that the emergency is over, COVID-19 is still a significant global issue. Here, we focus on recent developments in genetic and genomic research on COVID-19, and we give an outlook on state-of-the-art therapeutical approaches, as the pandemic is gradually transitioning to an endemic situation. The sequencing and characterization of rare alleles in different populations has made it possible to identify numerous genes that affect either susceptibility to COVID-19 or the severity of the disease. These findings provide a beginning to new avenues and pan-ethnic therapeutic approaches, as well as to potential genetic screening protocols. The causative virus, SARS-CoV-2, is still in the spotlight, but novel threatening virus could appear anywhere at any time. Therefore, continued vigilance and further research is warranted. We also note emphatically that to prevent future pandemics and other world-wide health crises, it is imperative to capitalize on what we have learnt from COVID-19: specifically, regarding its origins, the world's response, and insufficient preparedness. This requires unprecedented international collaboration and timely data sharing for the coordination of effective response and the rapid implementation of containment measures.

Patterns of Infectious Disease Associated With Injection Drug Use in Massachusetts.

BACKGROUND: Since 2014, multiple outbreaks of human immunodeficiency virus (HIV) among people who inject drugs have occurred across the United States along with hepatitis C virus (HCV), skin and soft tissue infections (SSTIs), and infective endocarditis (IE), creating a converging public health crisis. METHODS: We analyzed the temporal patterns of infectious disease and overdose using a hierarchical Bayesian distributed lag logistic regression model examining the probability that a given geographic area experienced at least 1 HIV case in a given month as a function of the counts/rates of overdose, HCV, SSTI, and IE and associated medical procedures at different lagged time periods. RESULTS: Current-month HIV is associated with increasing HCV cases, abscess incision and drainage, and SSTI cases, in distinct temporal patterns. For example, 1 additional HCV case occurring 5 and 7 months previously is associated with a 4% increase in the odds of observing at least 1 current-month HIV case in a given locale (odds ratios, 1.04 [90% credible interval {CrI}: 1.01-1.10] and 1.04 [90% CrI: 1.00-1.09]). No such associations were observed for echocardiograms, IE, or overdose. CONCLUSIONS: Lagged associations in other infections preceding rises in current-month HIV counts cannot be described as predictive of HIV outbreaks but may point toward newly discovered epidemics of injection drug use and associated clinical sequalae, prompting clinicians to screen patients more carefully for substance use disorder and associated infections.

Adventures in COVID-19 Policy Modeling: Education Edition.

PURPOSE OF REVIEW: To introduce readers to policy modeling, a multidisciplinary field of quantitative analysis, primarily used to help guide decision-making. This review focuses on the choices facing educational administrators, from K-12 to universities in the USA, as they confronted the COVID-19 pandemic. We survey three key model-based approaches to mitigation of SARS-CoV-2 spread in schools and on university campuses. RECENT FINDINGS: Frequent testing, coupled with strict attention to behavioral interventions to prevent further transmission can avoid large outbreaks on college campuses. K-12 administrators can greatly reduce the risks of severe outbreaks of COVID-19 in schools through various mitigation measures including classroom infection control, scheduling and cohorting strategies, staff and teacher vaccination, and asymptomatic screening. Safer re-opening of college and university campuses as well as in-person instruction for K-12 students is possible, under many though not all epidemic scenarios if rigorous disease control and screening programs are in place.

Surveillance for endemic infectious disease outbreaks: Adaptive sampling using profile likelihood estimation.

Outbreaks of an endemic infectious disease can occur when the disease is introduced into a highly susceptible subpopulation or when the disease enters a network of connected individuals. For example, significant HIV outbreaks among people who inject drugs have occurred in at least half a dozen US states in recent years. This motivates the current study: how can limited testing resources be allocated across geographic regions to rapidly detect outbreaks of an endemic infectious disease? We develop an adaptive sampling algorithm that uses profile likelihood to estimate the distribution of the number of positive tests that would occur for each location in a future time period if that location were sampled. Sampling is performed in the location with the highest estimated probability of triggering an outbreak alarm in the next time period. The alarm function is determined by a semiparametric likelihood ratio test. We compare the profile likelihood sampling (PLS) method numerically to uniform random sampling (URS) and Thompson sampling (TS). TS was worse than URS when the outbreak occurred in a location with lower initial prevalence than other locations. PLS had lower time to outbreak detection than TS in some but not all scenarios, but was always better than URS even when the outbreak occurred in a location with a lower initial prevalence than other locations. PLS provides an effective and reliable method for rapidly detecting endemic disease outbreaks that is robust to this uncertainty.

Opioid use disorder Cascade of care framework design: A roadmap.

Unintentional overdose deaths, most involving opioids, have eclipsed all other causes of US deaths for individuals less than 50 years of age. An estimated 2.4 to 5 million individuals have opioid use disorder (OUD) yet a minority receive treatment in a given year. Medications for OUD (MOUD) are the gold standard treatment for OUD however early dropout remains a major challenge for improving clinical outcomes. A Cascade of Care (CoC) framework, first popularized as a public health accountability strategy to stem the spread of HIV, has been adapted specifically for OUD. The CoC framework has been promoted by the NIH and several states and jurisdictions for organizing quality improvement efforts through clinical, policy, and administrative levers to improve OUD treatment initiation and retention. This roadmap details CoC design domains based on available data and potential linkages as individual state agencies and health systems typically rely on limited datasets subject to diverse legal and regulatory requirements constraining options for evaluations. Both graphical decision trees and catalogued studies are provided to help guide efforts by state agencies and health systems to improve data collection and monitoring efforts under the OUD CoC framework.

Suspected heroin-related overdoses incidents in Cincinnati, Ohio: A spatiotemporal analysis.

BACKGROUND: Opioid misuse and deaths are increasing in the United States. In 2017, Ohio had the second highest overdose rates in the US, with the city of Cincinnati experiencing a 50% rise in opioid overdoses since 2015. Understanding the temporal and geographic variation in overdose emergencies may help guide public policy responses to the opioid epidemic. METHODS AND FINDINGS: We used a publicly available data set of suspected heroin-related emergency calls (n = 6,246) to map overdose incidents to 280 census block groups in Cincinnati between August 1, 2015, and January 30, 2019. We used a Bayesian space-time Poisson regression model to examine the relationship between demographic and environmental characteristics and the number of calls within block groups. Higher numbers of heroin-related incidents were found to be associated with features of the built environment, including the proportion of parks (relative risk [RR] = 2.233; 95% credible interval [CI]: [1.075-4.643]), commercial (RR = 13.200; 95% CI: [4.584-38.169]), manufacturing (RR = 4.775; 95% CI: [1.958-11.683]), and downtown development zones (RR = 11.362; 95% CI: [3.796-34.015]). The number of suspected heroin-related emergency calls was also positively associated with the proportion of male population, the population aged 35-49 years, and distance to pharmacies and was negatively associated with the proportion aged 18-24 years, the proportion of the population with a bachelor's degree or higher, median household income, the number of fast food restaurants, distance to hospitals, and distance to opioid treatment programs. Significant spatial and temporal heterogeneity in the risks of incidents remained after adjusting for covariates. Limitations of this study include lack of information about the nature of incidents after dispatch, which may differ from the initial classification of being related to heroin, and lack of information on local policy changes and interventions. CONCLUSIONS: We identified areas with high numbers of reported heroin-related incidents and features of the built environment and demographic characteristics that are associated with these events in the city of Cincinnati. Publicly available information about opiate overdoses, combined with data on spatiotemporal risk factors, may help municipalities plan, implement, and target harm-reduction measures. In the US, more work is necessary to improve data availability in other cities and states and the compatibility of data from different sources in order to adequately measure and monitor the risk of overdose and inform health policies.

Bayesian adaptive algorithms for locating HIV mobile testing services.

BACKGROUND: We have previously conducted computer-based tournaments to compare the yield of alternative approaches to deploying mobile HIV testing services in settings where the prevalence of undetected infection may be characterized by 'hotspots'. We report here on three refinements to our prior assessments and their implications for decision-making. Specifically, (1) enlarging the number of geographic zones; (2) including spatial correlation in the prevalence of undetected infection; and (3) evaluating a prospective search algorithm that accounts for such correlation. METHODS: Building on our prior work, we used a simulation model to create a hypothetical city consisting of up to 100 contiguous geographic zones. Each zone was randomly assigned a prevalence of undetected HIV infection. We employed a user-defined weighting scheme to correlate infection levels between adjacent zones. Over 180 days, search algorithms selected a zone in which to conduct a fixed number of HIV tests. Algorithms were permitted to observe the results of their own prior testing activities and to use that information in choosing where to test in subsequent rounds. The algorithms were (1) Thompson sampling (TS), an adaptive Bayesian search strategy; (2) Besag York Mollié (BYM), a Bayesian hierarchical model; and (3) Clairvoyance, a benchmarking strategy with access to perfect information. RESULTS: Over 250 tournament runs, BYM detected 65.3% (compared to 55.1% for TS) of the cases identified by Clairvoyance. BYM outperformed TS in all sensitivity analyses, except when there was a small number of zones (i.e., 16 zones in a 4 × 4 grid), wherein there was no significant difference in the yield of the two strategies. Though settings of no, low, medium, and high spatial correlation in the data were examined, differences in these levels did not have a significant effect on the relative performance of BYM versus TS. CONCLUSIONS: BYM narrowly outperformed TS in our simulation, suggesting that small improvements in yield can be achieved by accounting for spatial correlation. However, the comparative simplicity with which TS can be implemented makes a field evaluation critical to understanding the practical value of either of these algorithms as an alternative to existing approaches for deploying HIV testing resources.

Comparison of treatment effect sizes from pivotal and postapproval trials of novel therapeutics approved by the FDA based on surrogate markers of disease: a meta-epidemiological study.

BACKGROUND: The U.S. Food and Drug Administration (FDA) often approves new drugs based on trials that use surrogate markers for endpoints, which involve certain trade-offs and may risk making erroneous inferences about the medical product's actual clinical effect. This study aims to compare the treatment effects among pivotal trials supporting FDA approval of novel therapeutics based on surrogate markers of disease with those observed among postapproval trials for the same indication. METHODS: We searched Drugs@FDA and PubMed to identify published randomized superiority design pivotal trials for all novel drugs initially approved by the FDA between 2005 and 2012 based on surrogate markers as primary endpoints and published postapproval trials using the same surrogate markers or patient-relevant outcomes as endpoints. Summary ratio of odds ratios (RORs) and difference between standardized mean differences (dSMDs) were used to quantify the average difference in treatment effects between pivotal and matched postapproval trials. RESULTS: Between 2005 and 2012, the FDA approved 88 novel drugs for 90 indications based on one or multiple pivotal trials using surrogate markers of disease. Of these, 27 novel drugs for 27 indications were approved based on pivotal trials using surrogate markers as primary endpoints that could be matched to at least one postapproval trial, for a total of 43 matches. For nine (75.0%) of the 12 matches using the same non-continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than postapproval trials. On average, treatment effects were 50% higher (more beneficial) in the pivotal than the postapproval trials (ROR 1.5; 95% confidence interval CI 1.01-2.23). For 17 (54.8%) of the 31 matches using the same continuous surrogate markers as trial endpoints, pivotal trials had larger treatment effects than the postapproval trials. On average, there was no difference in treatment effects between pivotal and postapproval trials (dSMDs 0.01; 95% CI -0.15-0.16). CONCLUSIONS: Many postapproval drug trials are not directly comparable to previously published pivotal trials, particularly with respect to endpoint selection. Although treatment effects from pivotal trials supporting FDA approval of novel therapeutics based on non-continuous surrogate markers of disease are often larger than those observed among postapproval trials using surrogate markers as trial endpoints, there is no evidence of difference between pivotal and postapproval trials using continuous surrogate markers.

Do Less Harm: Evaluating HIV Programmatic Alternatives in Response to Cutbacks in Foreign Aid.

BACKGROUND: Resource-limited nations must consider their response to potential contractions in international support for HIV programs. OBJECTIVE: To evaluate the clinical, epidemiologic, and budgetary consequences of alternative HIV program scale-back strategies in 2 recipient nations, the Republic of South Africa (RSA) and Côte d'Ivoire (CI). DESIGN: Model-based comparison between current standard (CD4 count at presentation of 0.260 × 109 cells/L, universal antiretroviral therapy [ART] eligibility, and 5-year retention rate of 84%) and scale-back alternatives, including reduced HIV detection, no ART or delayed initiation (when CD4 count is <0.350 × 109 cells/L), reduced investment in retention, and no viral load monitoring or second-line ART. DATA SOURCES: Published RSA- and CI-specific estimates of the HIV care continuum, ART efficacy, and HIV-related costs. TARGET POPULATION: HIV-infected persons, including future incident cases. TIME HORIZON: 5 and 10 years. PERSPECTIVE: Modified societal perspective, excluding time and productivity costs. OUTCOME MEASURES: HIV transmissions and deaths, years of life, and budgetary outlays (2015 U.S. dollars). RESULTS OF BASE-CASE ANALYSIS: At 10 years, scale-back strategies increase projected HIV transmissions by 0.5% to 19.4% and deaths by 0.6% to 39.1%. Strategies can produce budgetary savings of up to 30% but no more. Compared with the current standard, nearly every scale-back strategy produces proportionally more HIV deaths (and transmissions, in RSA) than savings. When the least harmful and most efficient alternatives for achieving budget cuts of 10% to 20% are applied, every year of life lost will save roughly $900 in HIV-related outlays in RSA and $600 to $900 in CI. RESULTS OF SENSITIVITY ANALYSIS: Scale-back programs, when combined, may result in clinical and budgetary synergies and offsets. LIMITATION: The magnitude and details of budget cuts are not yet known, nor is the degree to which other international partners might step in to restore budget shortfalls. CONCLUSION: Scaling back international aid to HIV programs will have severe adverse clinical consequences; for similar economic savings, certain programmatic scale-back choices result in less harm than others. PRIMARY FUNDING SOURCE: National Institutes of Health and Steve and Deborah Gorlin MGH Research Scholars Award.

Comparing frequency of booster vaccination to prevent severe COVID-19 by risk group in the United States.

There is a public health need to understand how different frequencies of COVID-19 booster vaccines may mitigate the risk of severe COVID-19, while accounting for waning of protection and differential risk by age and immune status. By analyzing United States COVID-19 surveillance and seroprevalence data in a microsimulation model, here we show that more frequent COVID-19 booster vaccination (every 6-12 months) in older age groups and the immunocompromised population would effectively reduce the burden of severe COVID-19, while frequent boosters in the younger population may only provide modest benefit against severe disease. In persons 75+ years, the model estimated that annual boosters would reduce absolute annual risk of severe COVID-19 by 199 (uncertainty interval: 183-232) cases per 100,000 persons, compared to a one-time booster vaccination. In contrast, for persons 18-49 years, the model estimated that annual boosters would reduce this risk by 14 (10-19) cases per 100,000 persons. Those with prior infection had lower benefit of more frequent boosting, and immunocompromised persons had larger benefit. Scenarios with emerging variants with immune evasion increased the benefit of more frequent variant-targeted boosters. This study underscores the benefit of considering key risk factors to inform frequency of COVID-19 booster vaccines in public health guidance and ensuring at least annual boosters in high-risk populations.

Early OxyContin Marketing Linked To Long-Term Spread Of Infectious Diseases Associated With Injection Drug Use.

The initial marketing of the opioid analgesic OxyContin in 1996 increased fatal drug overdoses over the course of the opioid epidemic in the US. However, the long-term impacts of this marketing on complications of injection drug use, a key feature of the ongoing crisis, are undetermined. This study evaluated the effects of exposure to initial OxyContin marketing on the long-term trajectories of injection drug use-related outcomes in the US. We used a difference-in-differences analysis to compare outcomes in states with high versus low exposure to initial marketing before and after the 2010 reformulation of OxyContin, which facilitated the use of illicit drugs and the spread of infectious disease. Exposure to initial OxyContin marketing statistically significantly increased rates of fatal synthetic opioid-related overdoses; acute hepatitis A, B, and C viral infections; and infective endocarditis-related deaths. The greatest burden of adverse long-term outcomes has been in states that experienced the highest exposure to early OxyContin marketing. Our findings indicate that OxyContin marketing decisions from the mid-1990s increased viral and bacterial complications of injection drug use and illicit opioid-related overdose deaths twenty-five years later.

Geographic and temporal trends in fentanyl-detected deaths in Connecticut, 2009-2019.

PURPOSE: Since 2012 fentanyl-detected fatal overdoses have risen from 4% of all fatal overdoses in Connecticut to 82% in 2019. We aimed to investigate the geographic and temporal trends in fentanyl-detected deaths in Connecticut during 2009-2019. METHODS: Data on the dates and locations of accidental/undetermined opioid-detected fatalities were obtained from Connecticut Office of the Chief Medical Examiner. Using a Bayesian space-time binomial model, we estimated spatiotemporal trends in the proportion of fentanyl-detected deaths. RESULTS: During 2009-2019, a total of 6,632 opioid deaths were identified. Among these, 3234 (49%) were fentanyl-detected. The modeled spatial patterns suggested that opioid deaths in northeastern Connecticut had higher probability of being fentanyl-detected, while New Haven and its neighboring towns and the southwestern region of Connecticut, primarily Greenwich, had a lower risk. Model estimates also suggested fentanyl-detected deaths gradually overtook the preceding non-fentanyl opioid-detected deaths across Connecticut. The estimated temporal trend showed the probability of fentanyl involvement increased substantially since 2014. CONCLUSIONS: Our findings suggest that geographic variation exists in the probability of fentanyl-detected deaths, and areas at heightened risk are identified. Further studies are warranted to explore potential factors contributing to the geographic heterogeneity and continuing dispersion of fentanyl-detected deaths in Connecticut.

Increased HIV Transmissions With Reduced Insurance Coverage for HIV Preexposure Prophylaxis: Potential Consequences of Braidwood Management v. Becerra.

A US federal court recently ruled against requiring health insurers to cover human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) under the Affordable Care Act. For every 10% decrease in PrEP coverage resulting from this ruling among US men who have sex with men, we estimate an additional 1140 HIV infections in the following year in that population.

The Dynamics of Infectious Diseases Associated With Injection Drug Use in Lawrence and Lowell, Massachusetts.

BACKGROUND: There are a wide variety of infectious complications of injection drug use. Understanding the trajectory of these complications might inform the development of an early warning system for human immunodeficiency virus (HIV) outbreaks that occur regularly among people who inject drugs (PWID). METHODS: A distributed lag Poisson regression model in the Bayesian setting was used to examine temporal patterns in the incidence of injection-associated infectious diseases and their association with HIV cases in Lawrence and Lowell, Massachusetts between 2005 and 2018. RESULTS: Current-month HIV counts are associated with fatal overdoses approximately 8 months prior, cases of infective endocarditis 10 months prior, and cases of skin and soft tissue infections and incision and drainage procedures associated with these infections 12 months prior. CONCLUSIONS: Collecting data on these other complications associated with injection drug use by public health departments may be important to consider because these complications may serve as input to a sentinel system to trigger early intervention and avert potential outbreaks of HIV.