Determinants of Type-Specific Human Papillomavirus Concordance Across Anatomic Sites in Young Men Who Have Sex With Men and Transgender Women, 3 U.S. Cities, 2016-2018.

BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections.

Remote surveillance and detection of SARS-CoV-2 transmission among household members in King County, Washington.

BACKGROUND: Early during the COVID-19 pandemic, it was important to better understand transmission dynamics of SARS-CoV-2, the virus that causes COVID-19. Household contacts of infected individuals are particularly at risk for infection, but delays in contact tracing, delays in testing contacts, and isolation and quarantine posed challenges to accurately capturing secondary household cases. METHODS: In this study, 346 households in the Seattle region were provided with respiratory specimen collection kits and remotely monitored using web-based surveys for respiratory illness symptoms weekly between October 1, 2020, and June 20, 2021. Symptomatic participants collected respiratory specimens at symptom onset and mailed specimens to the central laboratory in Seattle. Specimens were tested for SARS-CoV-2 using RT-PCR with whole genome sequencing attempted when positive. SARS-CoV-2-infected individuals were notified, and their household contacts submitted specimens every 2 days for 14 days. RESULTS: In total, 1371 participants collected 2029 specimens that were tested; 16 individuals (1.2%) within 6 households tested positive for SARS-CoV-2 during the study period. Full genome sequences were generated from 11 individuals within 4 households. Very little genetic variation was found among SARS-CoV-2 viruses sequenced from different individuals in the same household, supporting transmission within the household. CONCLUSIONS: This study indicates web-based surveillance of respiratory symptoms, combined with rapid and longitudinal specimen collection and remote contact tracing, provides a viable strategy to monitor households and detect household transmission of SARS-CoV-2. TRIAL REGISTRATION IDENTIFIER: NCT04141930, Date of registration 28/10/2019.

The Relationship Between Insertive Oral and Anal Sex and Select Measures of the Composition of the Urethral Microbiota Among Men Who Have Sex With Men.

BACKGROUND: Sexual behavior may influence the composition of the male urethral microbiota, but this hypothesis has not been tested in longitudinal studies of men who have sex with men (MSM). METHODS: From December 2014 to July 2018, we enrolled MSM with nongonococcal urethritis (NGU) attending a sexual health clinic. Men attended 5 in-clinic visits at 3-week intervals, collected weekly urine specimens at home, and reported daily antibiotics and sexual activity on weekly diaries. We applied broad-range 16S rRNA gene sequencing to urine. We used generalized estimating equations to estimate the association between urethral sexual exposures in the prior 7 days (insertive oral sex [IOS] only, condomless insertive anal intercourse [CIAI] only, IOS with CIAI [IOS + CIAI], or none) and Shannon index, number of species (observed, oral indicator, and rectal indicator), and specific taxa, adjusting for recent antibiotics, age, race/ethnicity, HIV, and preexposure prophylaxis. RESULTS: Ninety-six of 108 MSM with NGU attended ≥1 follow-up visit. They contributed 1140 person-weeks of behavioral data and 1006 urine specimens. Compared with those with no urethral sexual exposures, those with IOS only had higher Shannon index ( P = 0.03 ) but similar number of species and presence of specific taxa considered, adjusting for confounders; the exception was an association with Haemophilus parainfluenzae . CIAI only was not associated with measured aspects of the urethral microbiota. IOS + CIAI was only associated with presence of H. parainfluenzae and Haemophilus . CONCLUSIONS: Among MSM after NGU, IOS and CIAI did not seem to have a substantial influence on measured aspects of the composition of the urethral microbiota.

Changing genomic epidemiology of COVID-19 in long-term care facilities during the 2020-2022 pandemic, Washington State.

BACKGROUND: Long-term care facilities (LTCFs) are vulnerable to disease outbreaks. Here, we jointly analyze SARS-CoV-2 genomic and paired epidemiologic data from LTCFs and surrounding communities in Washington state (WA) to assess transmission patterns during 2020-2022, in a setting of changing policy. We describe sequencing efforts and genomic epidemiologic findings across LTCFs and perform in-depth analysis in a single county. METHODS: We assessed genomic data representativeness, built phylogenetic trees, and conducted discrete trait analysis to estimate introduction sizes over time, and explored selected outbreaks to further characterize transmission events. RESULTS: We found that transmission dynamics among cases associated with LTCFs in WA changed over the course of the COVID-19 pandemic, with variable introduction rates into LTCFs, but decreasing amplification within LTCFs. SARS-CoV-2 lineages circulating in LTCFs were similar to those circulating in communities at the same time. Transmission between staff and residents was bi-directional. CONCLUSIONS: Understanding transmission dynamics within and between LTCFs using genomic epidemiology on a broad scale can assist in targeting policies and prevention efforts. Tracking facility-level outbreaks can help differentiate intra-facility outbreaks from high community transmission with repeated introduction events. Based on our study findings, methods for routine tree building and overlay of epidemiologic data for hypothesis generation by public health practitioners are recommended. Discrete trait analysis added valuable insight and can be considered when representative sequencing is performed. Cluster detection tools, especially those that rely on distance thresholds, may be of more limited use given current data capture and timeliness. Importantly, we noted a decrease in data capture from LTCFs over time. Depending on goals for use of genomic data, sentinel surveillance should be increased or targeted surveillance implemented to ensure available data for analysis.

Risk of Subsequent Respiratory Virus Detection After Primary Virus Detection in a Community Household Study-King County, Washington, 2019-2021.

BACKGROUND: The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. METHODS: From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. RESULTS: Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03-2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant. CONCLUSIONS: Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection.

Development of novel composite data quality scores to evaluate facility-level data quality in electronic data in Kenya: a nationwide retrospective cohort study.

BACKGROUND: In this evaluation, we aim to strengthen Routine Health Information Systems (RHIS) through the digitization of data quality assessment (DQA) processes. We leverage electronic data from the Kenya Health Information System (KHIS) which is based on the District Health Information System version 2 (DHIS2) to perform DQAs at scale. We provide a systematic guide to developing composite data quality scores and use these scores to assess data quality in Kenya. METHODS: We evaluated 187 HIV care facilities with electronic medical records across Kenya. Using quarterly, longitudinal KHIS data from January 2011 to June 2018 (total N = 30 quarters), we extracted indicators encompassing general HIV services including services to prevent mother-to-child transmission (PMTCT). We assessed the accuracy (the extent to which data were correct and free of error) of these data using three data-driven composite scores: 1) completeness score; 2) consistency score; and 3) discrepancy score. Completeness refers to the presence of the appropriate amount of data. Consistency refers to uniformity of data across multiple indicators. Discrepancy (measured on a Z-scale) refers to the degree of alignment (or lack thereof) of data with rules that defined the possible valid values for the data. RESULTS: A total of 5,610 unique facility-quarters were extracted from KHIS. The mean completeness score was 61.1% [standard deviation (SD) = 27%]. The mean consistency score was 80% (SD = 16.4%). The mean discrepancy score was 0.07 (SD = 0.22). A strong and positive correlation was identified between the consistency score and discrepancy score (correlation coefficient = 0.77), whereas the correlation of either score with the completeness score was low with a correlation coefficient of -0.12 (with consistency score) and -0.36 (with discrepancy score). General HIV indicators were more complete, but less consistent, and less plausible than PMTCT indicators. CONCLUSION: We observed a lack of correlation between the completeness score and the other two scores. As such, for a holistic DQA, completeness assessment should be paired with the measurement of either consistency or discrepancy to reflect distinct dimensions of data quality. Given the complexity of the discrepancy score, we recommend the simpler consistency score, since they were highly correlated. Routine use of composite scores on KHIS data could enhance efficiencies in DQA at scale as digitization of health information expands and could be applied to other health sectors beyondHIV clinics.

Impact of differentiated service delivery models on 12-month retention in HIV treatment in Mozambique: an interrupted time-series analysis.

BACKGROUND: HIV treatment has been available in Mozambique since 2004, but coverage of, and retention in, antiretroviral therapy (ART) remain suboptimal. Therefore, to increase health system efficiency and reduce HIV-associated mortality, in November, 2018, the Ministry of Health launched national guidelines on implementing eight differentiated service delivery models (DSDMs) for HIV treatment. We assessed the effect of this implementation on retention in ART 12 months after initiation, and explored the associated effects of COVID-19. METHODS: In this uncontrolled interrupted time-series analysis, data were extracted from the Mozambique ART database, which contains data on individuals in ART care from 1455 health facilities providing ART in Mozambique. We included individual-level data from facilities that were providing ART at the beginning of the study period (Jan 1, 2016) and at the start of DSDM implementation (Dec 1, 2018). We compared the proportion of individuals retained in ART 12 months after initiation between the periods before (Jan 1, 2017, to Nov 30, 2018) and after (Dec 1, 2019, to June 30, 2021) implementation of the DSDMs, overall and stratified by sex and age. We applied a generalised estimating equation model with a working independence correlation and cluster-robust standard errors to account for clustering at the facility level. In a secondary analysis, we assessed the effect of COVID-19 response measures during the post-intervention period on ART retention. FINDINGS: The study included 613 facilities and 1 131 118 individuals who started ART during the inclusion period up to June 30, 2020, of whom 79 178 (7·0%) were children (age ≤14 years), 226 224 (20·0%) were adolescents and young adults (age 15-24 years), and 825 716 (73·0%) were adults (age ≥25 years). 731 623 (64·7%) were female and 399 495 (35·3%) were male. Introduction of the DSDMs was associated with an estimated increase of 24·5 percentage points (95% CI 21·1 to 28·0) in 12-month ART retention by the end of the study period, compared with the counterfactual scenario without DSDM implementation. By age, the smallest effect was estimated in children (6·1 percentage points, 1·3 to 10·9) and the largest effect in adolescents and young adults (28·8 percentage points, 24·2 to 33·4); by sex, a larger effect was estimated in males (29·7 percentage points, 25·6 to 33·7). Our analysis showed that COVID-19 had an overall negative effect on 12-month retention in ART compared with a counterfactual scenario based on the post-intervention period without COVID-19 (-10·0 percentage points, -18·2 to -1·8). INTERPRETATION: The implementation of eight DSDMs for HIV treatment had a positive impact on 12-month retention in ART. COVID-19 negatively influenced this outcome. FUNDING: None. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Sample Size Calculations for Stepped Wedge Designs with Treatment Effects that May Change with the Duration of Time under Intervention.

The stepped wedge design is often used to evaluate interventions as they are rolled out across schools, health clinics, communities, or other clusters. Most models used in the design and analysis of stepped wedge trials assume that the intervention effect is immediate and constant over time following implementation of the intervention (the "exposure time"). This is known as the IT (immediate treatment effect) assumption. However, recent research has shown that using methods based on the IT assumption when the treatment effect varies over exposure time can give extremely misleading results. In this manuscript, we discuss the need to carefully specify an appropriate measure of the treatment effect when the IT assumption is violated and we show how a stepped wedge trial can be powered when it is anticipated that the treatment effect will vary as a function of the exposure time. Specifically, we describe how to power a trial when the exposure time indicator (ETI) model of Kenny et al. (Statistics in Medicine, 41, 4311-4339, 2022) is used and the estimand of interest is a weighted average of the time-varying treatment effects. We apply these methods to the ADDRESS-BP trial, a type 3 hybrid implementation study designed to address racial disparities in health care by evaluating a practice-based implementation strategy to reduce hypertension in African American communities.

Care-seeking correlates of acute respiratory illness among sheltered adults experiencing homelessness in Seattle, WA, 2019: a community-based cross-sectional study.

Objective: Multifarious barriers to accessing healthcare services among people experiencing homelessness (PEH) lead to delays in seeking care for acute infections, including those caused by respiratory viruses. PEH are at high risk of acute respiratory illness (ARI)-related complications, especially in shelter settings that may facilitate virus spread, yet data characterizing healthcare utilization for ARI episodes among sheltered PEH remained limited. Methods: We conducted a cross-sectional study of viral respiratory infection among adult residents at two homeless shelters in Seattle, Washington between January and May 2019. We assessed factors associated with seeking medical care for ARI via self-report. We collected illness questionnaires and nasal swabs were tested for respiratory viruses by reverse transcription quantitative real-time PCR (RT-qPCR). Results: We observed 825 encounters from 649 unique participants; 241 (29.2%) encounters reported seeking healthcare for their ARI episode. Seasonal influenza vaccine receipt (adjusted prevalence ratio [aPR] 1.39, 95% CI 1.02-1.88), having health insurance (aPR 2.77, 95% CI 1.27-6.02), chronic lung conditions (aPR 1.55, 95% CI 1.12-2.15), and experiencing influenza-like-illness symptoms (aPR 1.63, 95% CI 1.20 - 2.20) were associated with increased likelihood of seeking care. Smoking (aPR 0.65, 95% CI 0.45-0.92) was associated with decreased likelihood of seeking care. Discussion: Findings suggest that care seeking for viral respiratory illness among PEH may be supported by prior engagement with primary healthcare services. Strategies to increase healthcare utilization may lead to earlier detection of respiratory viruses.

Incidence of SARS-CoV-2 infection and associated risk factors among staff and residents at homeless shelters in King County, Washington: an active surveillance study.

Homeless shelter residents and staff may be at higher risk of SARS-CoV-2 infection. However, SARS-CoV-2 infection estimates in this population have been reliant on cross-sectional or outbreak investigation data. We conducted routine surveillance and outbreak testing in 23 homeless shelters in King County, Washington, to estimate the occurrence of laboratory-confirmed SARS-CoV-2 infection and risk factors during 1 January 2020-31 May 2021. Symptom surveys and nasal swabs were collected for SARS-CoV-2 testing by RT-PCR for residents aged ≥3 months and staff. We collected 12,915 specimens from 2,930 unique participants. We identified 4.74 (95% CI 4.00-5.58) SARS-CoV-2 infections per 100 individuals (residents: 4.96, 95% CI 4.12-5.91; staff: 3.86, 95% CI 2.43-5.79). Most infections were asymptomatic at the time of detection (74%) and detected during routine surveillance (73%). Outbreak testing yielded higher test positivity than routine surveillance (2.7% versus 0.9%). Among those infected, residents were less likely to report symptoms than staff. Participants who were vaccinated against seasonal influenza and were current smokers had lower odds of having an infection detected. Active surveillance that includes SARS-CoV-2 testing of all persons is essential in ascertaining the true burden of SARS-CoV-2 infections among residents and staff of congregate settings.

Streptococcus pneumoniae nasal carriage patterns with and without common respiratory virus detections in households in Seattle, WA, USA before and during the COVID-19 pandemic.

Background: Respiratory viruses might influence Streptococcus pneumoniae nasal carriage and subsequent disease risk. We estimated the association between common respiratory viruses and semiquantitative S. pneumoniae nasal carriage density in a household setting before and during the COVID-19 pandemic. Methods: From November 2019-June 2021, we enrolled participants in a remote household surveillance study of respiratory pathogens. Participants submitted weekly reports of acute respiratory illness (ARI) symptoms. Mid-turbinate or anterior nasal swabs were self-collected at enrollment, when ARI occurred, and, in the second year of the study only, from household contacts after SARS-CoV-2 was detected in a household member. Specimens were tested using multiplex reverse-transcription PCR for respiratory pathogens, including S. pneumoniae, rhinovirus, adenovirus, common human coronavirus, influenza A/B virus, respiratory syncytial virus (RSV) A/B, human metapneumovirus, enterovirus, and human parainfluenza virus. We estimated differences in semiquantitative S. pneumoniae nasal carriage density, estimated by the inverse of S. pneumoniae relative cycle threshold (Crt) values, with and without viral detection for any virus and for specific respiratory viruses using linear generalized estimating equations of S. pneumoniae Crt values on virus detection adjusted for age and swab type and accounting for clustering of swabs within households. Results: We collected 346 swabs from 239 individuals in 151 households that tested positive for S. pneumoniae (n = 157 with and 189 without ≥1 viruses co-detected). Difficulty breathing, cough, and runny nose were more commonly reported among individuals with specimens with viral co-detection compared to without (15%, 80% and 93% vs. 8%, 57%, and 51%, respectively) and ear pain and headache were less commonly reported (3% and 26% vs. 16% and 41%, respectively). For specific viruses among all ages, semiquantitative S. pneumoniae nasal carriage density was greater with viral co-detection for enterovirus, RSV A/B, adenovirus, rhinovirus, and common human coronavirus (P < 0.01 for each). When stratified by age, semiquantitative S. pneumoniae nasal carriage density was significantly greater with viral co-detection among children aged <5 (P = 0.002) and 5-17 years (P = 0.005), but not among adults aged 18-64 years (P = 0.29). Conclusion: Detection of common respiratory viruses was associated with greater concurrent S. pneumoniae semiquantitative nasal carriage density in a household setting among children, but not adults.

Burden of long COVID among adults experiencing sheltered homelessness: a longitudinal cohort study in King County, WA between September 2020-April 2022.

BACKGROUND: People experiencing homelessness (PEH) are at increased risk for acquiring SARS-CoV-2, but the burden of long COVID in this population is unknown. METHODS: We conducted a matched prospective cohort study to assess the prevalence, characteristics, and impact of long COVID among sheltered PEH in Seattle, WA between September 2020-April 2022. Adults ≥ 18 years, residing across nine homeless shelters with active respiratory virus surveillance, were eligible to complete in-person baseline surveys and interval follow-up phone surveys. We included a subset of 22 COVID-19-positive cases who tested positive or inconclusive for SARS-CoV-2 and 44 COVID-19-negative controls who tested negative for SARS-CoV-2, frequency matched on age and sex. Among controls, 22 were positive and 22 were negative for one of 27 other respiratory virus pathogens. To assess the impact of COVID-19 on the risk of symptom presence at follow-up (day 30-225 post-enrollment test), we performed log-linear regression with robust standard errors, adjusting for confounding by shelter site and demographic variables determined a priori. RESULTS: Of 53 eligible COVID-19 cases, 22 (42%) completed ≥ 1 follow-up survey. While five (23%) cases reported ≥ 1 symptom at baseline, this increased to 77% (10/13) between day 30-59 and 33% (4/12) day 90 + . The most commonly reported symptoms day 30 + were fatigue (27%) and rhinorrhea (27%), with 8 (36%) reporting symptoms that interfered with or prevented daily activities. Four (33%) symptomatic cases reported receiving medical care outside of a medical provider at an isolation facility. Of 44 controls, 12 (27%) reported any symptoms day 90 + . Risk of any symptoms at follow-up was 5.4 times higher among COVID-19 cases compared to controls (95% CI: 2.7-10.5). CONCLUSIONS: Shelter residents reported a high prevalence of symptoms 30 + days after their SARS-CoV-2 detection, though few accessed medical care for persistent illness. The impact of COVID-19 extends beyond acute illness and may exacerbate existing challenges that marginalized populations face in maintaining their health and wellbeing.

Counterfactual estimation of efficacy against placebo for novel PrEP agents using external trial data: example of injectable cabotegravir and oral PrEP in women.

INTRODUCTION: Multiple antiretroviral agents have demonstrated efficacy for human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP). As a result, clinical trials of novel agents have transitioned from placebo- to active-controlled designs; however, active-controlled trials do not provide an estimate of efficacy versus no use of PrEP. Counterfactual placebo comparisons using other data sources could be employed to provide this information. METHODS: We compared the active-controlled study (HPTN 084) of injectable cabotegravir (CAB-LA) versus daily oral emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) among women from seven countries in Africa to three external, contemporaneous randomized HIV prevention trials from which we constructed counterfactual placebo estimates. We used direct standardization via analysis weights to achieve the same distribution of person-years between the external study and HPTN 084, across strata predictive of HIV risk (country and selected risk covariates). We estimated prevention efficacy against a counterfactual placebo to provide information on the use of CAB-LA and FTC/TDF compared to no intervention. We compared the counterfactual placebo findings for FTC/TDF to previous placebo-controlled trials, adjusted for observed adherence to daily pills. RESULTS: Distribution of age and baseline prevalence of gonorrhoea and chlamydia were similar among matched counterfactual placebo and observed HPTN 084 arms after standardization. Counterfactual estimates of CAB-LA versus placebo in all three settings showed a consistent risk reduction of 93%-94%, with lower bounds of the confidence intervals above 72%. Observed adherence (quantifiable tenofovir in plasma) in HPTN 084 was 54%-56%, and estimated efficacy of daily oral FTC/TDF against a counterfactual placebo was consistent with a predicted risk reduction of 39%-40% for this level of daily pill use. CONCLUSIONS: Counterfactual placebo rates of HIV acquisition derived from external trial data in similar locations and time can be used to support estimates of placebo-based efficacy of a novel HIV prevention agent. External trial data must be standardized to be representative of the clinical trial cohort testing the novel HIV prevention agent, accounting for confounders.

Respiratory syncytial virus and other respiratory virus infections in residents of homeless shelters - King County, Washington, 2019-2021.

Respiratory syncytial virus (RSV) causes disproportionate morbidity and mortality in vulnerable populations. We tested residents of homeless shelters in Seattle, Washington for RSV in a repeated cross-sectional study as part of community surveillance for respiratory viruses. Of 15 364 specimens tested, 35 had RSV detected, compared to 77 with influenza. The most common symptoms for both RSV and influenza were cough and rhinorrhea. Many individuals with RSV (39%) and influenza (58%) reported that their illness significantly impacted their ability to perform their regular activities. RSV and influenza demonstrated similar clinical presentations and burden of illness in vulnerable populations living in congregate settings.

Estimating benefits of using on-demand oral prep by MSM: A comparative modeling study of the US and Thailand.

Background: Daily and on-demand pre-exposure prophylaxis (PrEP) are effective at preventing HIV acquisition among men who have sex with men (MSM), but only daily PrEP is approved in the US. On-demand PrEP may improve uptake and adherence. We identify sub-groups of MSM who would benefit from on-demand PrEP and determine effectiveness achieved if individuals used their optimal regimens. Methods: Using data from the HPTN 067 study (study period 2012-2014), we created an individual-based stochastic model of HIV risk in two synthetic MSM populations with parameters separately estimated using data from Harlem, US, and Bangkok, Thailand. Agents were assigned daily and on-demand PrEP for six months each. Two personalized PrEP assignments: optimal, based on improved predicted effectiveness and reduced pill burden, and adherence-based, using daily PrEP adherence, were simulated for another six months. Findings: Simulated on-demand PrEP was optimal for approximately one-third of MSM. It was assigned mainly to those with low daily PrEP adherence (88% (Harlem), 95% (Bangkok) of MSM with daily PrEP adherence <40%). Mean effectiveness was slightly higher in the full synthetic population with optimal PrEP assignment compared to universal daily PrEP. Among MSM for whom on-demand PrEP was optimal, mean effectiveness improved by 18 (Harlem) and 7 percentage points (Bangkok). Comparable predicted effectiveness was achieved if on-demand PrEP was assigned to the population with daily PrEP adherence <50%. There was no advantage in assigning on-demand PrEP by sex act frequency. Interpretation: On-demand PrEP could benefit many MSM by increasing effectiveness or decreasing pill burden with similar effectiveness. On-demand PrEP may be an effective alternative to daily PrEP for individuals with difficulty taking daily PrEP consistently. Results were similar for Harlem and Bangkok, indicating that these conclusions were robust in populations with different overall adherence levels and may inform future public-health policies. Funding: US NIH grant UM1 AI068617.

Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021.

Genomic data provides useful information for public health practice, particularly when combined with epidemiologic data. However, sampling bias is a concern because inferences from nonrandom data can be misleading. In March 2021, the Washington State Department of Health, USA, partnered with submitting and sequencing laboratories to establish sentinel surveillance for SARS-CoV-2 genomic data. We analyzed available genomic and epidemiologic data during presentinel and sentinel periods to assess representativeness and timeliness of availability. Genomic data during the presentinel period was largely unrepresentative of all COVID-19 cases. Data available during the sentinel period improved representativeness for age, death from COVID-19, outbreak association, long-term care facility-affiliated status, and geographic coverage; timeliness of data availability and captured viral diversity also improved. Hospitalized cases were underrepresented, indicating a need to increase inpatient sampling. Our analysis emphasizes the need to understand and quantify sampling bias in phylogenetic studies and continue evaluation and improvement of public health surveillance systems.

Inadequate performance of a risk score to predict asymptomatic Neisseria gonorrhoeae and Chlamydia trachomatis infection among cisgender men who have sex with men.

OBJECTIVES: Epidemiological treatment of persons who are sexual contacts to partners with Neisseria gonorrhoeae (NG) and Chlamydia trachomatis (CT) often results in treatment of uninfected persons, which may increase the risk of antibiotic-resistant infections. We sought to identify the predictors of NG and/or CT infections to develop a risk score that could be used to limit epidemiological treatment to persons most likely to have these infections. METHODS: We included visits to the Public Health - Seattle & King County Sexual Health Clinic by asymptomatic cisgender men who have sex with men (MSM) aged ≥18 who presented as a sexual contact to partner(s) with CT or NG infection between 2011 and 2019. We used logistic regression to estimate the odds of CT and/or NG infections associated with demographic and clinical predictors, selecting the final set of predictors using the Akaike information criteria and obtaining score weights from model coefficients. We used a cross-validation approach to obtain average model discrimination from each of 10 models, leaving out 10% of the data, and evaluated sensitivity and specificity at various score cut-offs. RESULTS: The final model for predicting NG or CT infection included seven predictors (age <35 years, HIV status, receptive oral sex in the prior 2 months, CT diagnosis, condomless receptive anal intercourse, condomless insertive anal intercourse and methamphetamine use in the prior 12 months). Model discrimination, as measured by the receiver operating curve, was 0.60 (95% CI 0.54 to 0.66). Sensitivity for detection of infection was ≥90% for scores ≥3, ≥5 and ≥7; specificity for these cut-offs was <16%. At scores ≥9, ≥12 and ≥14, specificity increased but sensitivity decreased to ≤76%. CONCLUSIONS: Our risk score did not sufficiently discriminate between asymptomatic MSM with and without NG/CT infection. Additional studies evaluating epidemiological treatment as a standard of care in diverse populations are needed to guide best practices in the management of contacts to NG/CT infection.

Results from a test-and-treat study for influenza among residents of homeless shelters in King County, WA: A stepped-wedge cluster-randomized trial.

BACKGROUND: Persons experiencing homelessness face increased risk of influenza as overcrowding in congregate shelters can facilitate influenza virus spread. Data regarding on-site influenza testing and antiviral treatment within homeless shelters remain limited. METHODS: We conducted a cluster-randomized stepped-wedge trial of point-of-care molecular influenza testing coupled with antiviral treatment with baloxavir or oseltamivir in residents of 14 homeless shelters in Seattle, WA, USA. Residents ≥3 months with cough or ≥2 acute respiratory illness (ARI) symptoms and onset <7 days were eligible. In control periods, mid-nasal swabs were tested for influenza by reverse transcription polymerase chain reaction (RT-PCR). The intervention period included on-site rapid molecular influenza testing and antiviral treatment for influenza-positives if symptom onset was <48 h. The primary endpoint was monthly influenza virus infections in the control versus intervention periods. Influenza whole genome sequencing was performed to assess transmission and antiviral resistance. RESULTS: During 11/15/2019-4/30/2020 and 11/2/2020-4/30/2021, 1283 ARI encounters from 668 participants were observed. Influenza virus was detected in 51 (4%) specimens using RT-PCR (A = 14; B = 37); 21 influenza virus infections were detected from 269 (8%) intervention-eligible encounters by rapid molecular testing and received antiviral treatment. Thirty-seven percent of ARI-participant encounters reported symptom onset < 48 h. The intervention had no effect on influenza virus transmission (adjusted relative risk 1.73, 95% confidence interval [CI] 0.50-6.00). Of 23 influenza genomes, 86% of A(H1N1)pdm09 and 81% of B/Victoria sequences were closely related. CONCLUSION: Our findings suggest feasibility of influenza test-and-treat strategies in shelters. Additional studies would help discern an intervention effect during periods of increased influenza activity.