The detection of evolutionary transitions in influenza A (H3N2) viruses' antigenicity is a major obstacle to effective vaccine design and development. In this study, we describe Novel Influenza Virus A Detector (NIAViD), an unsupervised machine learning tool, adept at identifying these transitions, using the HA1 sequence and associated physico-chemical properties. NIAViD performed with 88.9% (95% CI, 56.5-98.0%) and 72.7% (95% CI, 43.4-90.3%) sensitivity in training and validation, respectively, outperforming the uncalibrated null model-33.3% (95% CI, 12.1-64.6%) and does not require potentially biased, time-consuming and costly laboratory assays. The pivotal role of the Boman's index, indicative of the virus's cell surface binding potential, is underscored, enhancing the precision of detecting antigenic transitions. NIAViD's efficacy is not only in identifying influenza isolates that belong to novel antigenic clusters, but also in pinpointing potential sites driving significant antigenic changes, without the reliance on explicit modelling of haemagglutinin inhibition titres. We believe this approach holds promise to augment existing surveillance networks, offering timely insights for the development of updated, effective influenza vaccines. Consequently, NIAViD, in conjunction with other resources, could be used to support surveillance efforts and inform the development of updated influenza vaccines.

Accurate forecasts can enable more effective public health responses during seasonal influenza epidemics. For the 2021-22 and 2022-23 influenza seasons, 26 forecasting teams provided national and jurisdiction-specific probabilistic predictions of weekly confirmed influenza hospital admissions for one-to-four weeks ahead. Forecast skill is evaluated using the Weighted Interval Score (WIS), relative WIS, and coverage. Six out of 23 models outperform the baseline model across forecast weeks and locations in 2021-22 and 12 out of 18 models in 2022-23. Averaging across all forecast targets, the FluSight ensemble is the 2(nd) most accurate model measured by WIS in 2021-22 and the 5(th) most accurate in the 2022-23 season. Forecast skill and 95% coverage for the FluSight ensemble and most component models degrade over longer forecast horizons. In this work we demonstrate that while the FluSight ensemble was a robust predictor, even ensembles face challenges during periods of rapid change.

INTRODUCTION: Antenatal care (ANC) interventions improve maternal and neonatal outcomes. However, access to ANC may be inequitable due to sociocultural, monetary and time factors. Examining drivers of ANC disparities may identify those amenable to policy change. METHODS: We conducted an ANC services equity analysis in selected public facilities in Geita, Tanzania, where most services are free to the end-user, and Atlantique, Benin, where every visit incurs user fees. Data on total ANC contacts, quality of care (QoC) indicators and wait times were collected from representative household surveys in the catchment of 40 clinics per country and were analysed by education and wealth. We used indices of inequality, concentration indices and Oaxaca-Blinder decompositions to determine the distribution, direction and magnitude of inequalities and their contributing factors. We assessed out-of-pocket expenses and the benefit incidence of government funding. RESULTS: ANC clients in both countries received less than the recommended minimum ANC contacts: 3.41 (95% CI 3.36 to 3.41) in Atlantique and 3.33 (95% CI 3.27 to 3.39) in Geita. Wealthier individuals had more ANC contacts than poorer ones at every education level in both countries; the wealthiest and most educated had two visits more than the poorest, least educated. In Atlantique, ANC attendees receive similar QoC regardless of socioeconomic status. In Geita, there are wide disparities in QoC received by education or wealth. In Atlantique, out-of-pocket expenses for the lowest wealth quintile are 2.7% of annual income compared with 0.8% for the highest, with user fees being the primary expense. In Geita, the values are 3.1% and 0.5%, respectively; transportation is the main expense. CONCLUSIONS: Inequalities in total ANC visits favouring wealthier, more educated individuals were apparent in both countries. In Atlantique, reduction of user-fees could improve ANC access. In Geita, training and equipping healthcare staff could improve QoC. Community health services could mitigate access barriers.

During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making.

BACKGROUND: Antenatal care provides unique opportunities to assess severe acute respiratory syndrome coronavirus 2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. We estimated seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid immunoglobulin G) among pregnant people, and evaluated transplacental transfer efficiency. OBJECTIVE AND DESIGN: We conducted a cross-sectional study to measure severe acute respiratory syndrome coronavirus 2 seroprevalence, and a prospective cohort study to longitudinally measure anti-nucleocapsid immunoglobulin G responses and transplacental transfer of maternally derived anti-nucleocapsid antibodies. METHODS: We screened pregnant people for the seroprevalence study between 9 December 2020 and 19 June 2021 for anti-nucleocapsid immunoglobulin G in Seattle, Washington. We enrolled anti-nucleocapsid immunoglobulin G positive people from the seroprevalence study or identified through medical records with positive reverse transcription polymerase chain reaction or antigen positive results in a prospective cohort between 9 December 2020 and 9 August 2022. RESULTS: In the cross-sectional study (N = 1284), 5% (N = 65) tested severe acute respiratory syndrome coronavirus 2 anti-nucleocapsid immunoglobulin G positive, including 39 (60%) without prior positive reverse transcription polymerase chain reaction results and 42 (65%) without symptoms. In the prospective cohort study (N = 107 total; N = 65 from the seroprevalence study), 86 (N = 80%) had anti-nucleocapsid immunoglobulin G positive results during pregnancy. Among 63 participants with delivery samples and prior anti-nucleocapsid positive results, 29 (46%) were anti-nucleocapsid immunoglobulin G negative by delivery. Of 34 remaining anti-nucleocapsid immunoglobulin G positive at delivery with paired cord blood, 19 (56%) had efficient transplacental anti-nucleocapsid immunoglobulin G antibody transfer. Median time from first anti-nucleocapsid immunoglobulin G positive to below positive antibody threshold was 19 weeks and did not differ by prior positive reverse transcription polymerase chain reaction status. CONCLUSIONS: Maternally derived severe acute respiratory syndrome coronavirus 2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants.

OBJECTIVES: Estimates of malaria burden and intervention uptake in Africa are primarily based on household surveys. However, their expense and infrequency limit their utility. We investigated whether data collected during antenatal care (ANC) can provide relevant information for decision-makers. METHODS: Malaria test positivity rates and questionnaire data from ANC attendees at 39 health facilities were compared to questionnaire data and positivity rates among children from two cross-sectional surveys in the facilities' corresponding catchment areas. RESULTS: Trends in parasitemia among ANC attendees were predictive of trends in parasitemia among children at the council level (mean absolute error 6.0%). Primigravid ANC attendees had the lowest rates of net ownership (modeled odds ratio, OR, 0.28, 95% confidence interval, CI, 0.19 - 0.40) and use (OR 0.58, 95% CI 0.42 - 0.79). ANC attendees reported higher levels of care seeking (OR 1.78, 95% CI 1.48 - 2.14), malaria testing (OR 4.16, 95% CI 3.44 - 5.04), and treatment for children with fever (OR 7.66, 95% CI 4.89 - 11.98) compared to women surveyed in households, raising concerns about social desirability bias disproportionately impacting ANC surveys. CONCLUSION: ANC surveillance is an effective strategy for tracking trends in malaria burden. More work is required to elucidate the value in administering questionnaires to ANC attendees.

Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information& Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44

Importance: Antenatal care provides unique opportunities to assess SARS-CoV-2 seroprevalence and antibody response duration after natural infection detected during pregnancy; transplacental antibody transfer may inform peripartum and neonatal protection. Objective(s): Estimate seroprevalence and durability of antibodies from natural infection (anti-nucleocapsid (anti-N) IgG) among pregnant people, and evaluate transplacental transfer efficiency. Design(s): Seroprevalence study: cross-sectional SARS-CoV-2 antibody screening among pregnant people December 9, 2020-June 19, 2021. Cohort study: Pregnant people screened anti-N IgG+ by Abbott Architect chemiluminescent immunoassay in seroprevalence study or identified through medical records with RT-PCR+ or antigen positive results enrolled in a prospective cohort December 9, 2020-June 30, 2022 to longitudinally measure anti-N IgG responses. We collected cord blood and assessed transplacental transfer of maternally-derived anti-N antibodies. Setting(s): Three hospitals and 14 affiliated clinics providing antenatal and delivery care, Seattle, Washington metropolitan area. Participant(s): Seroprevalence study: pregnant people were screened for SAR-CoV-2 anti-N IgG during routine care. Cohort study: Pregnant people with evidence of prior SARS-CoV-2 infection (screened anti-N IgG+ from seroprevalence study or identified with a RT-PCR+ or antigen positive result from medical records) were enrolled in a cohort study to longitudinally measure anti-N IgG responses. Exposure(s) (for observational studies): COVID-19 diagnosis, symptoms, and disease severity. Main Outcome(s) and Measure(s): Presence and durability of SARS-CoV-2 anti-N IgG, transplacental transfer of maternally-derived anti-N IgG. Result(s): Of 1289 pregnant people screened in the seroprevalence study, 5% (65) tested SARS-CoV-2 anti-N IgG+, including 39 (60%) without prior RT-PCR+ or antigen positive results and 53 (82%) without symptoms. Among 89 participants enrolled in the cohort study, 73 (82%) had anti-N IgG+ results during pregnancy. Among 49 participants with delivery samples 33 (67%) were anti-N IgG negative by delivery. Of 24 remaining anti-N IgG+ at delivery with paired cord blood samples, 12 (50%) had efficient transplacental anti-N IgG antibody transfer. Median time from first anti-N IgG to below positive antibody threshold was 17 weeks and did not differ by prior RT-PCR+ or antigen positive status. Conclusions and Relevance: Maternally-derived SARS-CoV-2 antibodies to natural infection may wane before delivery. Vaccines are recommended for pregnant persons to reduce severe illness and confer protection to infants. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license.

Background HIV testing and counseling is a key component of HIV prevention and the entry point into the treatment cascade, which improves for individual clinical outcomes and reduces onward HIV transmission. Current guidelines recommend at least annual testing for key populations. More frequent testing could provide health benefits, but these additional services increase the program the cost-effectiveness is not well-evaluated. Methods We used a compartmental mathematical model to simulate the health and economic impact of HIV testing one to four times per year for men who have sex with men, people who inject drugs, and female sex workers in Viet Nam. Model outcomes included costs, HIV infections, HIV-related deaths, and disability-adjusted life years (DALYs) associated with each scenario. We used an opportunity cost-based cost-effectiveness threshold of US $2,255 per DALY averted, discounted costs and health benefits at 3% annually, and used a time horizon from 2021 to 2030 to calculate incremental cost-effectiveness ratios (ICERs). Results Compared to the baseline scenario, more frequent HIV testing was estimated to incrementally avert 10.2%, 5.2%, 3.0%, and 1.6% discounted infections for one-, two-, three-, and four-tests per year, respectively. ICERs associated with each scenario ranged from $464, $1,190, $1,762, and $2,727 per DALY averted for one-, two-, three-, and four-tests per year, respectively. Conclusions Increased HIV testing frequency for key populations was projected to avert HIV incidence, mortality, and disability in Viet Nam and was cost-effective. Settings with a similar context should consider strategies on how to optimize retesting among key populations. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.

Soft tick relapsing fever (STRF) (also known as tickborne relapsing fever) is a rare infection caused by certain Borrelia spirochetes and transmitted to humans by soft-bodied Ornithodoros ticks. In the United States, acquisition of STRF is commonly associated with exposure to rustic cabins, camping, and caves. Antibiotic treatment is highly effective for STRF, but without timely treatment, STRF can result in severe complications, including death. No nationally standardized case definition for STRF exists; however, the disease is reportable in 12 states. This report summarizes demographic and clinical information for STRF cases reported during 2012-2021 from states where STRF is reportable. During this period, 251 cases were identified in 11 states. The median annual case count was 24. Most patients with STRF (55%) were hospitalized; no fatalities were reported. The geographic distribution and seasonal pattern of STRF have remained relatively constant since the 1990s. Persons should avoid rodent-infested structures and rodent habitats, such as caves, in areas where STRF is endemic. STRF surveillance, prevention, and control efforts would benefit from a standardized case definition and increased awareness of the disease among the public and clinicians.

BACKGROUND: While many malaria-endemic countries have health management information systems that can measure and report malaria trends in a timely manner, these routine systems have limitations. Periodic community cross-sectional household surveys are used to estimate malaria prevalence and intervention coverage but lack geographic granularity and are resource intensive. Incorporating malaria testing for all women at their first antenatal care (ANC) visit (i.e., ANC1) could provide a more timely and granular source of data for monitoring trends in malaria burden and intervention coverage. This article describes a protocol designed to assess if ANC-based surveillance could be a pragmatic tool to monitor malaria. METHODS: This is an observational, cross-sectional study conducted in Benin, Burkina Faso, Mozambique, Nigeria, Tanzania, and Zambia. Pregnant women attending ANC1 in selected health facilities will be tested for malaria infection by rapid diagnostic test and administered a brief questionnaire to capture key indicators of malaria control intervention coverage and care-seeking behaviour. In each location, contemporaneous cross-sectional household surveys will be leveraged to assess correlations between estimates obtained using each method, and the use of ANC data as a tool to track trends in malaria burden and intervention coverage will be validated. RESULTS: This study will assess malaria prevalence at ANC1 aggregated at health facility and district levels, and by gravidity relative to current pregnancy (i.e., gravida 1, gravida 2, and gravida 3 +). ANC1 malaria prevalence will be presented as monthly trends. Additionally, correlation between ANC1 and household survey-derived estimates of malaria prevalence, bed net ownership and use, and care-seeking will be assessed. CONCLUSION: ANC1-based surveillance has the potential to provide a cost-effective, localized measure of malaria prevalence that is representative of the general population and useful for tracking monthly changes in parasite prevalence, as well as providing population-representative estimates of intervention coverage and care-seeking behavior. This study will evaluate the representativeness of these measures and collect information on operational feasibility, usefulness for programmatic decision-making, and potential for scale-up of malaria ANC1 surveillance.

BACKGROUND: Measurement of malaria prevalence is conventionally estimated through infrequent cross-sectional household surveys that do not provide continuous information regarding malaria parasitaemia. Recent studies have suggested that malaria parasitaemia prevalence among women attending antenatal care (ANC) correlates with prevalence among children under 5 years old and that pregnant women could be a sentinel population for tracking malaria prevalence. In mainland Tanzania, 97% of women are tested for malaria parasitaemia during first ANC visits. However, acceptability among pregnant women and healthcare providers of collecting malaria risk factor data during ANC visits is limited. METHODS: A tablet-based questionnaire including 15 questions on insecticide-treated net ownership and use and care-seeking for febrile children was introduced at 40 healthcare facilities in Geita Region, Tanzania. Facilities were randomly selected from among those with 15-120 first ANC visits per month. To assess perspectives regarding introduction of the questionnaire, 21 semi-structured interviews were held with providers and facility in-charges at 12 facilities. Thirty pregnant and recently delivered women participated in focus group discussions at seven facilities to assess the acceptability of spending additional time answering questions about malaria risk. RESULTS: All pregnant women reported that introduction of ANC surveillance and spending 10 more minutes with providers answering questions about their health would be neutral or beneficial. They perceived being asked about their health as standard of care. Providers and in-charges reported that introduction of ANC surveillance was within their scope of practice. Nine of 21 indicated it could potentially benefit women's health. Six providers expressed concern about staffing shortages and need for reimbursement for extra time and noted that data management occurs after hours. CONCLUSIONS: Pregnant women and providers generally perceived ANC surveillance for malaria as acceptable and positive. Pregnant and recently delivered women saw this as a reasonable and even helpful intervention. To be seen as a part of standard practice, efforts are needed to ensure providers perceive a benefit for ANC clients and that staffing concerns are addressed. In addition, staff should receive feedback related to data submissions regarding malaria prevalence and risk factors among women at their facility, with actions to take.

OBJECTIVES: Key populations, including sex workers, men who have sex with men, and people who inject drugs, have a high risk of HIV and sexually transmitted infections. We assessed the health and economic impacts of different HIV and syphilis testing strategies among three key populations in Viet Nam using a dual HIV/syphilis rapid diagnostic test (RDT). SETTING: We used the spectrum AIDS impact model to simulate the HIV epidemic in Viet Nam and evaluated five testing scenarios among key populations. We used a 15-year time horizon and a provider perspective for costs. PARTICIPANTS: We simulate the entire population of Viet Nam in the model. INTERVENTIONS: We modelled five testing scenarios among key populations: (1) annual testing with an HIV RDT, (2) annual testing with a dual RDT, (3) biannual testing using dual RDT and HIV RDT, (4) biannual testing using HIV RDT and (5) biannual testing using dual RDT. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is incremental cost-effectiveness ratios. Secondary outcomes include HIV and syphilis cases. RESULTS: Annual testing using a dual HIV/syphilis RDT was cost-effective (US$10 per disability-adjusted life year (DALY)) and averted 3206 HIV cases and treated 27727 syphilis cases compared with baseline over 15 years. Biannual testing using one dual test and one HIV RDT (US$1166 per DALY), or two dual tests (US$5672 per DALY) both averted an additional 875 HIV cases, although only the former scenario was cost-effective. Annual or biannual HIV testing using HIV RDTs and separate syphilis tests were more costly and less effective than using one or two dual RDTs. CONCLUSIONS: Annual HIV and syphilis testing using dual RDT among key populations is cost-effective in Vietnam and similar settings to reach global reduction goals for HIV and syphilis.

SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action.

OBJECTIVES: To characterize contraceptive counseling experiences among women living with HIV (WLWH) receiving HIV care in Kenya. STUDY DESIGN: Sexually active, WLWH aged 15-49 years were purposively sampled from 109 high-volume HIV Care and Treatment Centers in Kenya between June and September 2016. Cross-sectional surveys were administered to enroll women on a tablet using Open Data Kit. Poisson generalized linear regression models adjusted for facility-level clustering were used to examine cofactors for receiving family planning (FP) counseling with a provider. RESULTS: Overall, 4805 WLWH were enrolled, 60% reported they received FP counseling during the last year, 72% of whom reported they were counseled about benefits of birth spacing and limiting. Most women who received FP counseling were married (64%) and discussed FP with their partner (78%). Use of FP in the last month (adjusted Prevalence Ratio [aPR]=1.74, 95% CI: 1.41-2.15, p<0.001), desire for children in >2 years (aPR=1.18, 95% CI: 1.09-1.28, p<0.001), and concern about contraceptive side-effects (aPR=1.13, 95% CI 1.02-1.25, p<0.05) were significantly higher among WLWH who received FP counseling compared to those that did not. CONCLUSIONS: Over one-third of WLWH did not receiving FP counseling with an HIV care provider during the last year, and counseling was more commonly reported among women who were using FP or desired children in >2 years. IMPLICATIONS: There are missed opportunities for FP counseling in HIV care. FP integration in HIV care could improve FP access and birth spacing or limiting among WLWH.

OBJECTIVE: Cervical cancer is the leading cause of cancer-related death among Kenyan women. It is important to identify how demographics and knowledge of cervical cancer are associated with screening to determine best practices for targeted screening efforts. METHODS: We conducted a sub-analysis of women who were asked about cervical cancer from a cross-sectional study of women attending large HIV care and treatment programs across Kenya between June and September 2016. RESULTS: 1671 of 3007 (56%) women reported ever being screened, 804 (48%) of whom were screened within the last 12 months. Prevalence of screening was highest among women who were older (Adjusted Prevalence Ratio [APR] age 35-49 versus 18-24: 2.26, 95% CI: 1.68-3.05, P<0.001), employed (APR: 1.55, 95% CI: 1.24-1.93, P<0.001), married (APR: 1.27, 95% CI: 1.01-1.59, P=0.047), had at least secondary education (APR: 1.45, 95% CI: 1.19-1.77, P<0.001), with longer time since HIV diagnosis (APR: 1.09/year average increase, 95% CI: 1.04-1.13, P<0.001). 36% knew cervical cancer is treatable. CONCLUSION: Characteristics linked to social or economic capital are correlated with cervical cancer screening. Integrating cervical cancer screening into HIV care and educating patients on the need for annual screening and potential treatment are important strategies for increasing screening uptake.

BACKGROUND: Dual HIV and syphilis testing might help to prevent mother-to-child transmission (MTCT) of HIV and syphilis through increased case detection and treatment. We aimed to model and assess the cost-effectiveness of dual testing during antenatal care in four countries with varying HIV and syphilis prevalence. METHODS: In this modelling study, we developed Markov models of HIV and syphilis in pregnant women to estimate costs and infant health outcomes of maternal testing at the first antenatal care visit with individual HIV and syphilis tests (base case) and at the first antenatal care visit with a dual rapid diagnostic test (scenario one). We additionally evaluated retesting during late antenatal care and at delivery with either individual tests (scenario two) or a dual rapid diagnosis test (scenario three). We modelled four countries: South Africa, Kenya, Colombia, and Ukraine. Strategies with an incremental cost-effectiveness ratio (ICER) less than the country-specific cost-effectiveness threshold (US$500 in Kenya, $750 in South Africa, $3000 in Colombia, and $1000 in Ukraine) per disability-adjusted life-year averted were considered cost-effective. FINDINGS: Routinely offering testing at the first antenatal care visit with a dual rapid diagnosis test was cost-saving compared with the base case in all four countries (ICER: -$26 in Kenya,-$559 in South Africa, -$844 in Colombia, and -$454 in Ukraine). Retesting during late antenatal care with a dual rapid diagnostic test (scenario three) was cost-effective compared with scenario one in all four countries (ICER: $270 in Kenya, $260 in South Africa, $2207 in Colombia, and $205 in Ukraine). INTERPRETATION: Incorporating dual rapid diagnostic tests in antenatal care can be cost-saving across countries with varying HIV prevalence. Countries should consider incorporating dual HIV and syphilis rapid diagnostic tests as the first test in antenatal care to support efforts to eliminate MTCT of HIV and syphilis. FUNDING: WHO, US Agency for International Development, and the Bill & Melinda Gates Foundation.

OBJECTIVES: Integrating family planning (FP) into routine HIV care and treatment are recommended by WHO guidelines to improve FP access among HIV-infected individuals in sub-Saharan Africa. This study sought to assess factors that influence the delivery of integrated FP services and the impact of facility-level integration of FP on contraceptive uptake among women living with HIV (WLWH). STUDY DESIGN: A national cross-sectional study was conducted among WLWH at HIV Care and Treatment centers with >1000 antiretroviral treatment (ART) clients per year. A mobile team visited 108 HIV Care and Treatment centers and administered surveys to key informants regarding facility attributes and WLWH regarding FP at these centers between June and September 2016. We classified facilities offering FP services within the same facility as 'integrated' facilities. RESULTS: 4805 WLWH were enrolled at 108 facilities throughout Kenya. The majority (73%) of facilities offered integrated FP services. They were more likely to be offered in public than private facilities (Prevalence Ratio [PR]: 1.86, 95% Confidence Interval [CI]: 1.11-3.11; p=0.02] and were more common in the Nyanza region than the Nairobi region (77% vs 35% respectively, p=0.06). Any contraceptive use (89% vs 80%), use of modern contraception (88% vs 80%), dual method use (40% vs 30%), long-acting reversible contraception (LARC) (28% vs 20%), and non-barrier short-term methods (34% vs 27%) were all significantly higher in facilities with integrated FP services (p<0.001). CONCLUSIONS: The majority of high volume facilities integrated FP services into HIV care. Integrating FP services may increase modern contraceptive use among WLWH.

INTRODUCTION: With the goal of eliminating hepatitis C virus (HCV) as a public health problem in Washington State, Public Health-Seattle & King County (PHSKC) designed a Hepatitis C Virus Test and Cure (HCV-TAC) data system to integrate surveillance, clinical, and laboratory data into a comprehensive database. The intent of the system was to promote identification, treatment, and cure of HCV-infected persons (ie, HCV care cascade) using a population health approach. MATERIALS AND METHODS: The data system automatically integrated case reports received via telephone and fax from health care providers and laboratories, hepatitis test results reported via electronic laboratory reporting, and data on laboratory and clinic visits reported by 6 regional health care systems. PHSKC examined patient-level laboratory test results and established HCV case classification using Council of State and Territorial Epidemiologists criteria, classifying patients as confirmed if they had detectable HCV RNA. RESULTS: The data enabled PHSKC to report the number of patients at various stages along the HCV care cascade. Of 7747 HCV RNA-positive patients seen by a partner site, 5377 (69%) were assessed for severity of liver fibrosis, 3932 (51%) were treated, and 2592 (33%) were cured. PRACTICE IMPLICATIONS: Data supported local public heath surveillance and HCV program activities. The data system could serve as a foundation for monitoring future HCV prevention and control programs.

High rates of homologous recombination (HR) in the bacterial plant pathogen Xylella fastidiosa have been previously detected. This study aimed to determine the extent and explore the ecological significance of HR in the genomes of recombinants experimentally generated by natural transformation and wild-type isolates. Both sets of strains displayed widespread HR and similar average size of recombined fragments consisting of random events (2-10 kb) of inter- and intrasubspecific recombination. A significantly higher proportion and greater lengths (>10 kb, maximum 31.5 kb) of recombined fragments were observed in subsp. morus and in strains isolated in Europe from intercepted coffee plants shipped from the Americas. Such highly recombinant strains pose a serious risk of emergence of novel variants, as genetically distinct and formerly geographically isolated genotypes are brought in close proximity by global trade. Recently recombined regions in wild-type strains included genes involved in regulation and signaling, host colonization, nutrient acquisition, and host evasion, all fundamental traits for X. fastidiosa ecology. Identification of four recombinant loci shared between wild-type and experimentally generated recombinants suggests potential hotspots of recombination in this naturally competent pathogen. These findings provide insights into evolutionary forces possibly affecting the adaptive potential to colonize the host environments of X. fastidiosa.

OBJECTIVES: To estimate medical expenditures attributable to older adult falls using a methodology that can be updated annually to track these expenditures over time. DESIGN: Population data from the National Vital Statistics System (NVSS) and cost estimates from the Web-based Injury Statistics Query and Reporting System (WISQARS) for fatal falls, quasi-experimental regression analysis of data from the Medicare Current Beneficiaries Survey (MCBS) for nonfatal falls. SETTING: U.S. population aged 65 and older during 2015. PARTICIPANTS: Fatal falls from the 2015 NVSS (N=28,486); respondents to the 2011 MCBS (N=3,460). MEASUREMENTS: Total spending attributable to older adult falls in the United States in 2015, in dollars. RESULTS: In 2015, the estimated medical costs attributable to fatal and nonfatal falls was approximately $50.0 billion. For nonfatal falls, Medicare paid approximately $28.9 billion, Medicaid $8.7 billion, and private and other payers $12.0 billion. Overall medical spending for fatal falls was estimated to be $754 million. CONCLUSION: Older adult falls result in substantial medical costs. Measuring medical costs attributable to falls will provide vital information about the magnitude of the problem and the potential financial effect of effective prevention strategies.

OBJECTIVES: To characterize uptake and correlates of effective contraceptive use postpartum. STUDY DESIGN: We analyzed data from a national, cross-sectional evaluation of prevention of mother-to-child HIV transmission programs that enrolled women attending 6-week or 9-month infant immunization visits at 120 Kenyan maternal and child health clinics. We classified women who resumed sexual activity postpartum and did not desire a child within 2years as having a need for family planning (FP). RESULTS: We included 955 (94%) of 1012 women 8-10months postpartum in the analysis. Mean age was 25.8years and 36% were primigravidas. By 9-months postpartum 62% of all women used contraception and 59% used effective contraception (injectables, implants, intrauterine devices [IUDs], oral contraceptives [OCs], and tubal ligations). Most contraceptive users (61%) used injectables, followed by implants (10%), OCs (6%), IUDs (4%), and condoms alone (2%). The majority (n=733, 77%) had a need for FP and 67% of 733 women with FP need used effective contraception. Among women with a need for FP, effective contraception use was higher among those who discussed FP in postnatal care (PNC) than who did not discuss FP in PNC (Prevalence Ratio (PR) for PNC alone: 1.35 (95% Confidence Interval [CI]:1.16-1.58; PR for PNC and antenatal care [ANC]:1.42, 95% CI: 1.21-1.67; p=.001 for both). CONCLUSIONS: Two-thirds of postpartum women with a need for FP used effective contraception at 9-months postpartum, and use was associated with discussing FP during PNC. IMPLICATIONS: Integrating FP counseling in ANC/PNC could be an effective strategy to increase effective contraception use.

BACKGROUND: Pregnancy is associated with changes in hematological and biochemistry values, yet there are no African reference intervals for clinical management of pregnant women. We sought to 1) develop laboratory reference intervals during pregnancy and up to 24 weeks postpartum and 2) determine the proportion of women in a previous clinical trial who would be misclassified as having out-of-range values using reference intervals from a United States (U.S.) population. METHODS AND FINDINGS: This was a longitudinal sub-study of 120 clinically healthy, HIV-uninfected, self-selected pregnant women seeking antenatal care services at either of two public hospitals in western Kenya. Blood specimens were obtained from consented women at gestational ages 28 and 36 weeks and at 2, 6, 14 and 24 weeks postpartum. Median and 95% reference intervals were calculated for immune-hematological and biochemistry parameters and compared to reference intervals from a Kenyan and United States (U.S.) population, using Wilcoxon tests. Differences with p≤0.05 were considered significant. Some hematological parameters, including hemoglobin and neutrophils showed significant variations compared to reference intervals for non-pregnant women. Hemoglobin values were significantly lower during pregnancy but were comparable to the values in non-pregnant women by 6 weeks postpartum. CD4, CD8 and platelets were significantly elevated in early postpartum but declined gradually, reaching normal levels by 24 weeks postpartum. Using the new hemoglobin reference levels from this study to estimate prevalence of 'out of range' values in a prior Kisumu research cohort of pregnant/postpartum women, resulted in 0% out of range values, in contrast to 96.3% using US non-pregnant reference values. CONCLUSION: There were substantial differences in U.S. and Kenyan values for immune-hematological parameters among pregnant/postpartum women, specifically in red blood cell parameters in late pregnancy and 2 weeks postpartum. Use of U.S. reference intervals markedly increases likelihood of out of range values, highlighting the need for suitable locally developed reference intervals.

The exposure to respirable crystalline silica (RCS) in the mining industry is a recognized occupational hazard. The assessment and monitoring of the exposure to RCS is limited by two main factors: (1) variability of the silica percent in the mining dust and (2) lengthy off-site laboratory analysis of collected samples. The monitoring of respirable dust via traditional or real-time techniques is not adequate. A solution for on-site quantification of RCS in dust samples is being investigated by the Office of Mine Safety and Health Research, a division of the National Institute for Occupational Safety and Health. The use of portable Fourier transform infrared analyzers in conjunction with a direct-on-filter analysis approach is proposed. The progress made so far, the necessary steps in progress, and the application of the monitoring solution to a small data set is presented. When developed, the solution will allow operators to estimate RCS immediately after sampling, resulting in timelier monitoring of RCS for self-assessment of compliance at the end of the shift, more effective engineering monitoring, and better evaluation of control technologies.

OBJECTIVES: Respondent-driven sampling (RDS) is a new data collection methodology used to estimate characteristics of hard-to-reach groups, such as the HIV prevalence in drug users. Many national public health systems and international organizations rely on RDS data. However, RDS reporting quality and available reporting guidelines are inadequate. We carried out a systematic review of RDS studies and present Strengthening the Reporting of Observational Studies in Epidemiology for RDS Studies (STROBE-RDS), a checklist of essential items to present in RDS publications, justified by an explanation and elaboration document. STUDY DESIGN AND SETTING: We searched the MEDLINE (1970-2013), EMBASE (1974-2013), and Global Health (1910-2013) databases to assess the number and geographical distribution of published RDS studies. STROBE-RDS was developed based on STROBE guidelines, following Guidance for Developers of Health Research Reporting Guidelines. RESULTS: RDS has been used in over 460 studies from 69 countries, including the USA (151 studies), China (70), and India (32). STROBE-RDS includes modifications to 12 of the 22 items on the STROBE checklist. The two key areas that required modification concerned the selection of participants and statistical analysis of the sample. CONCLUSION: STROBE-RDS seeks to enhance the transparency and utility of research using RDS. If widely adopted, STROBE-RDS should improve global infectious diseases public health decision making.

Reduced basal ganglia function has been associated with fatigue in neurologic disorders, as well as in patients exposed to chronic immune stimulation. Patients with chronic fatigue syndrome (CFS) have been shown to exhibit symptoms suggestive of decreased basal ganglia function including psychomotor slowing, which in turn was correlated with fatigue. In addition, CFS patients have been found to exhibit increased markers of immune activation. In order to directly test the hypothesis of decreased basal ganglia function in CFS, we used functional magnetic resonance imaging to examine neural activation in the basal ganglia to a reward-processing (monetary gambling) task in a community sample of 59 male and female subjects, including 18 patients diagnosed with CFS according to 1994 CDC criteria and 41 non-fatigued healthy controls. For each subject, the average effect of winning vs. losing during the gambling task in regions of interest (ROI) corresponding to the caudate nucleus, putamen, and globus pallidus was extracted for group comparisons and correlational analyses. Compared to non-fatigued controls, patients with CFS exhibited significantly decreased activation in the right caudate (p = 0.01) and right globus pallidus (p = 0.02). Decreased activation in the right globus pallidus was significantly correlated with increased mental fatigue (r2 = 0.49, p = 0.001), general fatigue (r2 = 0.34, p = 0.01) and reduced activity (r2 = 0.29, p = 0.02) as measured by the Multidimensional Fatigue Inventory. No such relationships were found in control subjects. These data suggest that symptoms of fatigue in CFS subjects were associated with reduced responsivity of the basal ganglia, possibly involving the disruption of projections from the globus pallidus to thalamic and cortical networks.

Miners are exposed to silica-bearing dust which can lead to silicosis, a potentially fatal lung disease. Currently, airborne silica is measured by collecting filter samples and sending them to a laboratory for analysis. Since this may take weeks, a field method is needed to inform decisions aimed at reducing exposures. This study investigates a field-portable Fourier transform infrared (FTIR) method for end-of-shift (EOS) measurement of silica on filter samples. Since themethod entails localized analyses, spatial uniformity of dust deposition can affect accuracy and repeatability. The study, therefore, assesses the influence of radial deposition uniformity on the accuracy of the method. Using laboratory-generated Minusil and coal dusts and three different types of sampling systems, multiple sets of filter samples were prepared. All samples were collected in pairs to create parallel sets for training and validation. Silica was measured by FTIR at nine locations across the face of each filter and the data analyzed using a multiple regression analysis technique that compared various models for predicting silica mass on the filters using different numbers of "analysis shots." It was shown that deposition uniformity is independent of particle type (kaolin vs. silica), which suggests the role of aerodynamic separation is negligible. Results also reflected the correlation between the location and number of shots versus the predictive accuracy of the models. The coefficient of variation (CV) for the models when predicting mass of validation samples was 4%-51% depending on the number of points analyzed and the type of sampler used, which affected the uniformity of radial deposition on the filters. It was shown that using a single shot at the center of the filter yielded predictivity adequate for a field method, (93% return, CV approximately 15%) for samples collected with 3-piece cassettes.

Several assumptions determine whether respondent-driven sampling (RDS) is an appropriate sampling method to use with a particular group, including the population being recruited must know one another as members of the group (i.e., injection drug users [IDUs] must know each other as IDUs) and be networked and that the sample size is small relative to the overall size of the group. To assess these three assumptions, we analyzed city-specific data collected using RDS through the US National HIV Behavioral Surveillance System among IDUs in 23 cities. Overall, 5% of non-seed participants reported that their recruiter was "a stranger." 20 cities with multiple field sites had ≥1 cross-recruitment, a proxy for linked networks. Sample sizes were small in relation to the IDU population size (median = 2.3%; range: 0.6%- 8.0%). Researchers must evaluate whether these three assumptions were met to justify the basis for using RDS to sample specific populations.

BACKGROUND: During 2003-2005, the National HIV Behavioral Surveillance System (NHBS) enrolled men who have sex with men (MSM) from 12 different venue types in 15 metropolitan areas in the United States. Our goal was to examine whether limiting NHBS enrollment venues to gay bars and dance clubs could increase efficiency without changing the overall results and conclusions. METHODS: We used logistic regression analysis to compare the demographic characteristics and reported HIV risk behaviors among MSM enrolled in gay bars and dance clubs with those enrolled in sex venues and those enrolled in other venues. RESULTS: Of the 11,471 eligible men included in the analysis, 6419 (56%) were enrolled at bars and clubs, 481 (4%) at sex venues, and 4571 (40%) at other venues. Compared with men enrolled at bars and clubs, men enrolled at sex venues were more likely to be older, of nonwhite race/ethnicity, bisexual, infrequent gay venue attendees, and to have 10 or more male sex partners in the past 12 months. Men enrolled at other venues were more likely to be older and less likely to use noninjecting drugs in the past 12 months. The absolute differences in these characteristics between men enrolled in bars and clubs and those enrolled in comparison venue categories were small in most instances. CONCLUSIONS: Although the differences in characteristics by venue category were not large in magnitude, there was evidence that restricting NHBS enrollment to bars and clubs would affect national estimates of behavioral risk factors among MSM.