OBJECTIVES: To describe patterns of medication for opioid use disorder (MOUD) during pregnancies in the opioid use disorder (OUD) cohort of MAT-LINK, a sentinel surveillance network of pregnancies at US clinical sites. METHODS: Seven clinical sites providing care for pregnant people with OUD collected electronic health record data. Pregnancies were included in this analysis if (1) the pregnancy outcome occurred between January 2014 and August 2021, (2) the person had OUD, and (3) there was any electronic health record-documented MOUD during pregnancy. Analyses describing MOUD type, demographic characteristics, and timing during pregnancy were performed. RESULTS: Among 3911 pregnancies with any documented MOUD, more than 90% of pregnancies with methadone were to publicly insured people, which was greater than percentages for pregnancies with other MOUD. Buprenorphine with naloxone and naltrexone were two MOUD types that were increasingly common among pregnant people in recent years. In most pregnancies, prenatal care and MOUD were first documented in the same trimester. During the first, second, and third trimesters, there were 37%, 61%, and 91% of pregnancies with MOUD, respectively. Approximately 87% (n = 3412) had only 1 documented MOUD type, versus 2 or 3 types. However, discontinuity in MOUD across trimesters was still observed. CONCLUSIONS: In MAT-LINK's OUD cohort, the overall frequency of MOUD improved over the course of pregnancy. Contextual factors, such as insurance status and year of pregnancy outcome, might influence MOUD type. Prenatal care and MOUD might be facilitators for one another; however, there are still opportunities to improve early linkage and continuous access to both prenatal care and MOUD during pregnancy.

Hand hygiene is a cost-effective preventive measure to reduce transmission of infectious diseases. Yet, a quarter of the global population lack access to even a basic handwashing facility. | Forthcoming WHO and UNICEF guidelines on hand hygiene in community settings will provide evidence-based recommendations to guide action. | According to consulted future guideline end-users, sustainable implementation of such recommendations to improve hand hygiene requires government-led system-strengthening approaches that build sustainable and resilient national systems. | System-strengthening plans should be underpinned by a comprehensive situational analysis and needs assessment, and monitored on an ongoing basis for course correction where necessary. | Execution of system-strengthening plans should be integrated with existing programmes. | Health sector leadership is required to drive this agenda.

BACKGROUND: Cost-effectiveness analysis of HIV self-testing using patient-level data from a randomized clinical trial can inform HIV prevention funding decisions. Cost-effectiveness analysis using net benefit regression addresses the sampling uncertainty in the trial data and the variability of policymakers' willingness to pay (WTP). METHODS: We used published data from a 12-month longitudinal randomized clinical trial that enrolled 2665 men who sex with men (MSM) randomly assigned to the self-testing arm (participants receiving self-test kits) and control arm (participants receiving standard-of-care), and the self-testing arm identified 48 additional new HIV cases. We used net benefit regression to investigate the cost-effectiveness of an HIV self-testing intervention, which compared the incremental cost per new HIV diagnosis with policymakers' WTP thresholds. We addressed the uncertainties in estimating the incremental cost and the policymakers' WTP per new diagnosis through the incremental net benefit (INB) regression and cost-effectiveness acceptability curve (CEAC) analyses. RESULTS: From the healthcare provider's perspective, the INB analysis showed a positive net-benefit of HIV self-testing compared to standard-of-care when policymakers' WTP per new HIV diagnosis was $9,365 (95% CI: $5,700 - $25,500) or higher. The CEAC showed that the probability of HIV self-testing being cost-effective compared to standard-of-care was 58% and >99% at a WTP of $10 000 and $50 000 per new HIV diagnosis, respectively. CONCLUSION: The INB and CEAC analyses suggest that HIV self-testing has the potential to be cost-effective for relatively low values of policymakers' WTP.

The Lancet Series on Work and Health1, 2, 3 recognises that changes in the world of work are causing new occupational hazards to physical and mental health and increasing health inequalities within and between countries. These changes have profound implications for official workers’ health data and monitoring systems, which have become a global health priority as the world seeks to reach the Sustainable Development Goals (SDGs).4, 5 These monitoring systems are public goods that provide international organisations, governments, and communities the evidence base for policy and practice that ensures health for all workers. We argue that these monitoring systems must respond to changing working environments by expanding capture of workers’ rights, working conditions, and health inequalities. We outline normative data and monitoring products to reach this systemic shift and provide the public health vision for this new direction. | | No worker should die or get ill because of their work, or be left behind in occupational health protection and promotion. All workers are entitled to the human rights to: health;6 a clean, healthy, and sustainable environment; and a safe and healthy working environment.7 However, WHO and the International Labour Organization (ILO) estimate that annually 2 million deaths and 90 million disability-adjusted life-years are attributable to selected occupational risk factors.8 Recognition is growing that improving workers’ health and health equity requires action on the social and environmental determinants of health. Examples include strengthened evidence on the effects of the emerging psychosocial hazard of long working hours on cardiovascular disease,9 and the environmental and climate crises strengthening attention to workers’ environmental and climatic hazards (eg, air pollution and heat exposures). Occupational health policy increasingly comprises health equity analysis and targets. The WHO/ILO joint estimates show geographical and socioeconomic health inequalities—an increased number of deaths is noted among workers in Africa, South-East Asia, and the Western Pacific, and among men and people aged 55 years or older.8 People working in the informal economy, and migrant, outdoor, and front-line workers are often especially disadvantaged. Health-care workers, despite working in a sector that aims to restore, protect, and promote health, often face hazardous working conditions and are exposed to pathogens (eg, SARS-CoV-2), violence, and long working hours, among others. Ongoing changes in working environments (eg, globalisation, automation, digitisation, new pandemics, environmental pollution, and climate change) exacerbate these inequalities. Ultimately, unhealthy working conditions act as barriers for realising workers’ rights to health, population health, and health equity, and threaten the goal of achieving the SDGs globally.

BACKGROUND: HIV testing is an entry point to access HIV care and prevention services. Building Healthy Online Communities (BHOC) developed a website (TakeMeHome.org) where participants can order HIV home test kits. The purpose of this study was to analyze the costs and impact of the TakeMeHome program. METHODS: We estimated the costs of TakeMeHome across all participating jurisdictions for the first year of the program. We estimated program costs using purchase orders and invoices, contracts, and allocation of staff time, and the costs included website design, participant recruitment, administration and overhead, HIV self-test kits, and shipping and handling. Primary outcomes of the analysis were total program cost, cost per HIV test, and cost per new HIV diagnosis. RESULTS: TakeMeHome distributed 5,323 HIV self-tests to 4,859 participants over a 12-month period. The total program cost over this period was $314,870. The cost per HIV test delivered was estimated at $59, and the cost per person tested was $65. The program identified 18 (0.6% positivity) confirmed new HIV diagnoses that were verified with surveillance data in 7 health jurisdictions at $169,890. The cost per confirmed new HIV diagnosis was estimated at $9,440. CONCLUSIONS: The TakeMeHome program delivered HIV self-testing at a reasonable cost, and the program may be a cost-effective use of HIV prevention resources. The public-private partnership can be an effective mechanism to validate HIV diagnoses identified with self-testing and provide HIV prevention and linkage to care services.

BACKGROUND: The polio eradication endgame required the withdrawal of Sabin type 2 from the oral poliovirus vaccine and introduction of one or more dose of inactivated poliovirus vaccine (IPV) into routine immunisation schedules. However, the duration of single-dose IPV immunity is unknown. We aimed to address this deficiency. METHODS: In this phase 4, open-label, non-randomised clinical trial, we assessed single-dose IPV immunity. Two groups of infants or children were screened: the first group had previously received IPV at 14 weeks of age or older (previous IPV group; age >2 years); the second had not previously received IPV (no previous IPV group; age 7-12 months). At enrolment, all participants received an IPV dose. Children in the no previous IPV group received a second IPV dose at day 30. Blood was collected three times in each group: on days 0, 7, and 30 in the previous IPV group and on days 0, 30, and 37 in the no previous IPV group. Poliovirus antibody was measured by microneutralisation assay. Immunity was defined as the presence of a detectable antibody or a rapid anamnestic response (ie, priming). We used the χ(2) to compare proportions and the Mann-Whitney U test to assess continuous variables. To assess safety, vaccinees were observed for 30 min, caregivers for each participating child reported adverse events after each follow-up visit and were questioned during each follow-up visit regarding any adverse events during the intervening period. Adverse events were recorded and graded according to the severity of clinical symptoms. The study is registered with ClinicalTrials.gov, NCT03723837. FINDINGS: From Nov 18, 2018, to July 31, 2019, 502 participants enrolled in the study, 458 (255 [65%] boys and 203 [44%] girls) were included in the per protocol analysis: 234 (93%) in the previous IPV group and 224 (90%) in the no previous IPV group. In the previous IPV group, 28 months after one IPV dose 233 (>99%) of 234 children had persistence of poliovirus type 2 immunity (100 [43%] of 234 children were seropositive; 133 [99%] of 134 were seronegative and primed). In the no previous IPV group, 30 days after one IPV dose all 224 (100%) children who were type 2 poliovirus naive had seroconverted (223 [>99%] children) or were primed (one [<1%]). No adverse events were deemed attributable to study interventions. INTERPRETATION: A single IPV dose administered at 14 weeks of age or older is highly immunogenic and induces nearly universal type 2 immunity (seroconversion and priming), with immunity persisting for at least 28 months. The polio eradication initiative should prioritise first IPV dose administration to mitigate the paralytic burden caused by poliovirus type 2. FUNDING: WHO and Rotary International.

BACKGROUND: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000). METHODS: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch. RESULTS: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes. CONCLUSIONS: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies. FUNDING: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210]). | Salmonella Typhi (Typhi) is a type of bacteria that causes typhoid fever. More than 110,000 people die from this disease each year, predominantly in areas of sub-Saharan Africa and South Asia with limited access to safe water and sanitation. Clinicians use antibiotics to treat typhoid fever, but scientists worry that the spread of antimicrobial-resistant Typhi could render the drugs ineffective, leading to increased typhoid fever mortality. The World Health Organization has prequalified two vaccines that are highly effective in preventing typhoid fever and may also help limit the emergence and spread of resistant Typhi. In low resource settings, public health officials must make difficult trade-off decisions about which new vaccines to introduce into already crowded immunization schedules. Understanding the local burden of antimicrobial-resistant Typhi and how it is spreading could help inform their actions. The Global Typhoid Genomics Consortium analyzed 13,000 Typhi genomes from 110 countries to provide a global overview of genetic diversity and antimicrobial-resistant patterns. The analysis showed great genetic diversity of the different strains between countries and regions. For example, the H58 Typhi variant, which is often drug-resistant, has spread rapidly through Asia and Eastern and Southern Africa, but is less common in other regions. However, distinct strains of other drug-resistant Typhi have emerged in other parts of the world. Resistance to the antibiotic ciprofloxacin was widespread and accounted for over 85% of cases in South Africa. Around 70% of Typhi from Pakistan were extensively drug-resistant in 2020, but these hard-to-treat variants have not yet become established elsewhere. Variants that are resistant to both ciprofloxacin and ceftriaxone have been identified, and azithromycin resistance has also appeared in several different variants across South Asia. The Consortium’s analyses provide valuable insights into the global distribution and transmission patterns of drug-resistant Typhi. Limited genetic data were available fromseveral regions, but data from travel-associated cases helped fill some regional gaps. These findings may help serve as a starting point for collective sharing and analyses of genetic data to inform local public health action. Funders need to provide ongoing supportto help fill global surveillance data gaps. | eng

INTRODUCTION: The COVID-19 pandemic and its associated social distancing policies such as lockdowns and quarantine influenced people's lives and health behaviors. We comprehensively assessed national trends in sales of cigarettes, cigars, e-cigarettes, and over-the-counter nicotine replacement therapy (NRT) products before and during the pandemic, allowing for cross-product comparisons. Stockpiling behavior was also assessed. METHODS: We used US national tobacco and over-the-counter NRT retail store scanner data (excluding internet, specialty/vape store, and prescription sales) collected at 4-week intervals by NielsenIQ from December 2018 to June 2021. We applied an interrupted time-series model to assess differences in tobacco product and NRT unit sales before and during the pandemic. We defined the prepandemic period as December 16, 2018, through April 4, 2020, pandemic as starting on April 5, 2020, through June 26, 2021, and the stockpiling period as one 4-week period before the pandemic started. RESULTS: Four-week cigarette, e-cigarette, and cigar unit sales on average increased by 11.5% (P = .006), 37.1% (P < .001), and 26.1% (P < .001) respectively, while 4-week NRT unit sales decreased on average by 13.1% (P < .001), during the pandemic compared with the prepandemic period. Stockpiling was associated with increases in sales of all tobacco products and NRT products. CONCLUSION: Unit sales of assessed tobacco products increased while NRT unit sales decreased during the COVID-19 pandemic, compared with the prepandemic period. These changes may suggest an increase in the intensity of tobacco product use or stockpiling of tobacco products among people who use tobacco.

Background The incidence of enteric fever, an invasive bacterial infection caused by typhoidal Salmonellae, is largely unknown in regions lacking blood culture surveillance. New serologic markers have proven accurate in diagnosing enteric fever, but whether they could be used to reliably estimate population-level incidence is unknown.Methods We collected longitudinal blood samples from blood culture-confirmed enteric fever cases enrolled from surveillance studies in Bangladesh, Nepal, Pakistan, and Ghana and conducted cross-sectional serosurveys in the catchment areas of each surveillance site. We used ELISAs to measure quantitative IgA and IgG antibody responses to Hemolysin E (HlyE) and S. Typhi lipopolysaccharide (LPS). We used Bayesian hierarchical models to fit two-phase power-function decay models to the longitudinal antibody responses among enteric fever cases and used the joint distributions of the peak antibody titers and decay rate to estimate population-level incidence rates from cross-sectional serosurveys.Findings The longitudinal antibody kinetics for all antigen-isotypes were similar across countries and did not vary by clinical severity. The seroincidence of typhoidal Salmonella infection among children &lt;5 years ranged between 58.5 per 100 person-years (95% CI: 42.1 - 81.4) in Dhaka, Bangladesh to 6.6 (95% CI: 4.3-9.9) in Kavrepalanchok, Nepal, and followed the same rank order as clinical incidence estimates.Interpretation The approach described here has the potential to expand the geographic scope of typhoidal Salmonella surveillance and generate incidence estimates that are comparable across geographic regions and time.Funding This work was supported by the Bill and Melinda Gates Foundation (INV-000572).Evidence before this study Previous studies have identified serologic responses to two antigens (Hemolysin E [HlyE] and Salmonella lipopolysaccharide [LPS]) as promising diagnostic markers of acute typhoidal Salmonella infection. We reviewed the evidence for seroepidemiology tools for enteric fever available as of November 01, 2021, by searching the National Library of Medicine article database and medRxiv for preprint publications, published in English, using the terms “enteric fever”, “typhoid fever”, “Salmonella Typhi”, “Salmonella Paratyphi”, “typhoidal Salmonella”, “Hemolysin E”, “Salmonella lipopolysaccharide”, “seroconversion”, “serosurveillance”, “seroepidemiology”, “seroprevalence” and “seropositivity.” We found no studies using HlyE or LPS as markers to measure the incidence or prevalence of enteric fever in a population. Anti-Vi IgG responses were used as a marker of population seroprevalence in cross-sectional studies conducted in South Africa, Fiji, and Nepal, but were not used to calculate population-based incidence estimates.Added value of this study We developed and validated a method to estimate typhoidal Salmonella incidence in cross-sectional population samples using antibody responses measured from dried blood spots. First, using longitudinal dried blood spots collected from over 1400 blood culture-confirmed cases in four countries, we modeled the longitudinal dynamics of antibody responses for up to two years following infection, accounting for heterogeneity in antibody responses and age-dependence. We found that longitudinal antibody responses were highly consistent across four countries on two continents and did not differ by clinical severity. We then used these antibody kinetic parameters to estimate incidence in population-based samples in six communities across the four countries, where concomitant population-based incidence was measured using blood cultures. Seroincidence estimates were much higher than blood-culture-based case estimates across all six sites, suggestive of a high incidence of asymptomatic or unrecognized infections. Still, the rank order of seroincidence and culture-based incidence rates were the same, with the highest rates in Bangladesh and lowest in Ghana.Implications of all the available evidence Many a -risk low- and middle-income countries lack data on typhoid incidence needed to inform and evaluate vaccine introduction. Even in countries where incidence estimates are available, data are typically geographically and temporally sparse due to the resources necessary to initiate and sustain blood culture surveillance. We found that typhoidal Salmonella infection incidence can be estimated from community-based serosurveys using dried blood spots, representing an efficient and scalable approach for generating the typhoid burden data needed to inform typhoid control programs in resource-constrained settings.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was funded by th eBill and Melinda Gates Foundation (grant INV-000572)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:Institutional Review Boards in the United States (Centers for Disease Control and Prevention; Stanford University Institutional Review Board), Bangladesh (Bangladesh Institute of Child Health Ethical Review Committee), Nepal (Nepal Health Research Council Ethical Review Board), Pakistan (AKU Ethic Review Committee and Pakistan National Bioethics Committee), Korea (International Vaccine Institute IRB), Belgium (Institute of Tropical Medicine Antwerp Institutional Review Board) and Ghana (Komfo Anokye Teaching Hospital, Committee on Human Research, Publication and Ethics) approved the study forms and protocols.I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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 produced in the present study are available upon reasonable request to the authors

Background We compared influenza antibody titers among vaccinated and unvaccinated pregnant and non-pregnant women.Methods During 1st June – 30th September 2018, four groups of cohort participants - vaccinated pregnant, unvaccinated pregnant, vaccinated non-pregnant, and unvaccinated non-pregnant women were selected by matching age, gestational age, and the week of vaccination. Serum antibody titers against each strain of 2018 Southern Hemisphere inactivated trivalent influenza vaccine (IIV3) were assessed by hemagglutination inhibition (HI) assay on Day 0 (pre-vaccination) and Day 28 (one month post-vaccination) serum samples. Geometric mean titer (GMT), GMT ratio (GMR), seroconversion (defined as ≥4 fold increase in HI titer), and seroprotection (i.e. HI titer ≥1:40) were compared across the study groups using multilevel regression analyses, controlling for previous year vaccination from medical records and baseline antibody levels.Results A total of 132 participants were enrolled in the study (33 in each of the four study groups). The baseline GMTs were similar for influenza A(H1N1), A(H3N2), and B vaccine strains among all four groups (all p-values &gt;0.05). After one month, both vaccinated groups had significantly higher GMT, GMR, seroconversion, and seroprotection than their unvaccinated controls (all p-values &lt;0.05). The seroconversion rate was over 60% for any strain among the vaccinated groups, with the highest (88.8%) observed against A(H1N1) in the vaccinated pregnant group. Similarly, at least 75% of the vaccinated participants developed seroprotective antibody levels against all three strains; the highest seroprotection was found against A(H3N2) at 92.6% among vaccinated non-pregnant participants. Pregnant women had similar antibody responses (post-vaccination GMT, GMR, seroconversion, and seroprotection) to non-pregnant women for all three strains of IIV3 (all p&gt;0.05).Conclusions The 2018 seasonal IIV3 was immunogenic against all three vaccine strains and pregnancy did not seem to alter the immune response to IIV3. These findings support the current influenza vaccination recommendations for pregnant women.Competing Interest StatementThe authors have declared no competing interest.Clinical TrialThai Clinical Trials Registry ID: TCTR20201014004Funding StatementThis study was partially supported by the Nakhon Phanom Provincial Hospital Foundation (ref no. NP 0032.202.3/7) secured by KP and SN. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.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:The study protocol was reviewed and approved by the Ethical Review Committee of Thammasat University (Ref no. MTU-EC-ES-4-217/60). Approval of local ethics committee of Nakhon Phanom Hospital (No. NP-EC11-No.4/2560) was also received prior to the data collection.All 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 relevant data are within the paper and the supporting files.

Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of Typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens, and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with twelve variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on their ability to detect Salmonella Typhi and feasibility. Salmonella Typhi strains, Ty21a and Ty2, were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via qPCR. Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses including the Salmonella Typhi concentrations they are best suited for with a range of positive detections observed as low as 0.1-0.001 CFU Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned. 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-NC-ND 4.0 International license.

Salmonella enterica serovar (Salmonella Typhi) is the causative bacterial agent of typhoid fever. Environmental surveillance of wastewater and wastewater-impacted surface waters has proven effective in monitoring various pathogens and has recently been applied to Salmonella Typhi. This study evaluated eight sample collection and concentration methods with 12 variations currently being developed and used for Salmonella Typhi surveillance globally to better understand the performance of each method based on its ability to detect Salmonella Typhi and its feasibility. Salmonella Typhi strains Ty21a and Ty2 were seeded to influent wastewater at known concentrations to evaluate the following methods: grab sampling using electropositive filters, centrifugation, direct enrichment, or membrane filtration and trap sampling using Moore swabs. Concentrated samples underwent nucleic acid extraction and were detected and/or quantified via quantitative polymerase chain reaction (qPCR). Results suggest that all methods tested can be successful at concentrating Salmonella Typhi for subsequent detection by qPCR, although each method has its own strengths and weaknesses, including the Salmonella Typhi concentration it is best suited for, with a range of positive detections observed as low as 0.1-0.001 colony-forming units (CFU) Ty21a/mL and 0.01 CFU Ty2/mL. These factors should be considered when identifying a method for environmental surveillance and will greatly depend on the use case planned.

Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. 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.

Following its emergence in Wuhan, China, in late November or early December 2019, the SARS-CoV-2 virus has rapidly spread throughout the world. On March 11, 2020, the World Health Organization declared Coronavirus Disease 2019 (COVID-19) a pandemic. Genome sequencing of SARS-CoV-2 strains allows for the reconstruction of transmission history connecting these infections. Here, we analyze 346 SARS-CoV-2 genomes from samples collected between 20 February and 15 March 2020 from infected patients in Washington State, USA. We found that the large majority of SARS-CoV-2 infections sampled during this time frame appeared to have derived from a single introduction event into the state in late January or early February 2020 and subsequent local spread, strongly suggesting cryptic spread of COVID-19 during the months of January and February 2020, before active community surveillance was implemented. We estimate a common ancestor of this outbreak clade as occurring between 18 January and 9 February 2020. From genomic data, we estimate an exponential doubling between 2.4 and 5.1 days. These results highlight the need for large-scale community surveillance for SARS-CoV-2 introductions and spread and the power of pathogen genomics to inform epidemiological understanding.

PROBLEM: Medication for opioid use disorder (MOUD) is recommended for persons with opioid use disorder (OUD) during pregnancy. However, knowledge gaps exist about best practices for management of OUD during pregnancy and these data are needed to guide clinical care. PERIOD COVERED: 2014-2021. DESCRIPTION OF THE SYSTEM: Established in 2019, the Maternal and Infant Network to Understand Outcomes Associated with Medication for Opioid Use Disorder During Pregnancy (MAT-LINK) is a surveillance network of seven clinical sites in the United States. Boston Medical Center, Kaiser Permanente Northwest, The Ohio State University, and the University of Utah were the initial clinical sites in 2019. In 2021, three clinical sites were added to the network (the University of New Mexico, the University of Rochester, and the University of South Florida). Persons receiving care at the seven clinical sites are diverse in terms of geography, urbanicity, race and ethnicity, insurance coverage, and type of MOUD received. The goal of MAT-LINK is to capture demographic and clinical information about persons with OUD during pregnancy to better understand the effect of MOUD on outcomes and, ultimately, provide information for clinical care and public health interventions for this population. MAT-LINK maintains strict confidentiality through robust information technology architecture. MAT-LINK surveillance methods, population characteristics, and evaluation findings are described in this inaugural surveillance report. This report is the first to describe the system, presenting detailed information on funding, structure, data elements, and methods as well as findings from a surveillance evaluation. The findings presented in this report are limited to selected demographic characteristics of pregnant persons overall and by MOUD treatment status. Clinical and outcome data are not included because data collection and cleaning have not been completed; initial analyses of clinical and outcome data will begin in 2023. RESULTS: The MAT-LINK surveillance network gathered data on 5,541 reported pregnancies with a known pregnancy outcome during 2014-2021 among persons with OUD from seven clinical sites. The mean maternal age was 29.7 (SD = ±5.1) years. By race and ethnicity, 86.3% of pregnant persons were identified as White, 25.4% as Hispanic or Latino, and 5.8% as Black or African American. Among pregnant persons, 81.6% had public insurance, and 84.4% lived in urban areas. Compared with persons not receiving MOUD during pregnancy, those receiving MOUD during pregnancy were more likely to be older and White and to have public insurance. The evaluation of the surveillance system found that the initial four clinical sites were not representative of demographics of the South or Southwest regions of the United States and had low representation from certain racial and ethnic groups compared with the overall U.S. population; however, the addition of three clinical sites in 2021 made the surveillance network more representative. Automated extraction and processing improved the speed of data collection and analysis. The ability to add new clinical sites and variables demonstrated the flexibility of MAT-LINK. INTERPRETATION: MAT-LINK is the first surveillance system to collect comprehensive, longitudinal data on pregnant person-infant dyads with perinatal outcomes associated with MOUD during pregnancy from multiple clinical sites. Analyses of clinical site data demonstrated different sociodemographic characteristics between the MOUD and non-MOUD treatment groups. PUBLIC HEALTH ACTIONS: MAT-LINK is a timely and flexible surveillance system with data on approximately 5,500 pregnancies. Ongoing data collection and analyses of these data will provide information to support clinical and public health guidance to improve health outcomes among pregnant persons with OUD and their children.

In 2020, an estimated 2.7 million people in the US had opioid use disorder, increasing their risk of opioid-related morbidity and mortality. While jurisdictional vulnerability assessments (JVA) of opioid-related outcomes have been conducted previously in the US, there has been no unifying methodological framework. Between 2019 and 2021, we prepared ten JVAs, in collaboration with the Council of State and Territorial Epidemiologists, the Centers for Disease Control and Prevention, and state public health agencies, to evaluate the risk for opioid-involved overdose (OOD) fatalities and related consequences. Our aim is to share the framework we developed for these ten JVAs, based on our study of the work of Van Handel et al. from 2016, as well as a summary of 18 publicly available assessments of OOD or associated hepatitis C virus infection vulnerability. We developed a three-tiered framework that can be applied by jurisdictions based on the number of units of analysis (e.g., counties, ZIP Codes, census tracts): under 10 (Tier 1), 10 to <50 (Tier 2), and 50 or more (Tier 3). We calculated OOD vulnerability indices based on variable ranks, weighted variable ranks, or multivariable regressions, respectively, for the three tiers. We developed thematic maps, conducted spatial analyses, and visualized service provider locations, drive-time service areas, and service accessibility relative to OOD risk. The methodological framework and examples of our findings from several jurisdictions can be used as a foundation for future assessments and help inform policies to mitigate the impact of the opioid overdose crisis.

INTRODUCTION: Most e-cigarettes contain highly addictive nicotine. This study assessed trends in nicotine strength in e-cigarettes sold in the United States during January 2017-March 2022. AIMS AND METHODS: We obtained January 2017-March 2022 national retail e-cigarette sales data from NielsenIQ. We assessed monthly average nicotine strength overall, by e-cigarette product and flavor type, and manufacturer. A Joinpoint regression model assessed the magnitude and significance of changes in nicotine strength. RESULTS: During January 2017-March 2022, monthly average nicotine strength of e-cigarette products increased from 2.5% to 4.4%, an average of 0.8% per month (p < .001). Monthly average nicotine strength of disposable e-cigarettes increased the most (average monthly percentage change [AMPC] = 1.26%, p < .001) as compared to prefilled pods (AMPC = 0.6%, p < .001) and e-liquids (AMPC = 0.5%, p = .218). Monthly average nicotine strength for all flavors of e-cigarette products increased except for mint-flavored products. Increases were greatest for beverage-flavored products (AMPC = 2.1%, p < .001), followed by menthol-flavored products (AMPC = 1.2%, p < .001). Among the top 10 e-cigarette manufacturers assessed, monthly average nicotine strength decreased for Juul Labs products from 5% to 4.7% (AMPC = -0.1%, p < .001) but increased significantly for five manufacturers' products and remained unchanged at 5%-6% for four manufacturers' products. CONCLUSIONS: Monthly average nicotine strength of e-cigarette products increased overall, for most product and flavor types, and for some manufacturers in the United States during the study period. Imposing maximum limits on nicotine strength of e-cigarettes together with other evidence-based tobacco control strategies can help reduce the use of e-cigarettes among youth and increase tobacco product cessation among adults. IMPLICATIONS: From January 2017 to March 2022, the monthly average nicotine strength of disposable e-cigarettes increased substantially and exceeded prefilled pods since May 2020. E-cigarettes with menthol flavor and youth-appealing flavors, like fruit, also had sharp increases in monthly average nicotine strength. Among the top 10 e-cigarette manufacturers, monthly average nicotine strength increased or remained unchanged at a high nicotine level for all manufacturers' products, except Juul Lab's products. Comprehensive strategies including restricting sales of all flavored e-cigarettes, restricting youth tobacco product access, and imposing maximum limits on nicotine strength may help reduce youth e-cigarette use and increase tobacco cessation.

CONTEXT: Digital video-based behavioral interventions are effective tools for improving HIV care and treatment outcomes. OBJECTIVE: To assess the costs of the Positive Health Check (PHC) intervention delivered in HIV primary care settings. DESIGN, SETTING, AND INTERVENTION: The PHC study was a randomized trial evaluating the effectiveness of a highly tailored, interactive video-counseling intervention delivered in 4 HIV care clinics in the United States in improving viral suppression and retention in care. Eligible patients were randomized to either the PHC intervention or the control arm. Control arm participants received standard of care (SOC), and intervention arm participants received SOC plus PHC. The intervention was delivered on computer tablets in the clinic waiting rooms. The PHC intervention improved viral suppression among male participants. A microcosting approach was used to assess the program costs, including labor hours, materials and supplies, equipment, and office overhead. PARTICIPANTS: Persons with HIV infection, receiving care in participating clinics. MAIN OUTCOME MEASURES: The primary outcome was the number of patients virally suppressed, defined as having fewer than 200 copies/mL by the end of their 12-month follow-up. RESULTS: A total of 397 (range across sites [range], 95-102) participants were enrolled in the PHC intervention arm, of whom 368 participants (range, 82-98) had viral load data at baseline and were included in the viral load analyses. Of those, 210 (range, 41-63) patients were virally suppressed at the end of their 12-month follow-up visit. The overall annual program cost was $402 274 (range, $65 581-$124 629). We estimated the average program cost per patient at $1013 (range, $649-$1259) and the cost per patient virally suppressed at $1916 (range, $1041-$3040). Recruitment and outreach costs accounted for 30% of PHC program costs. CONCLUSIONS: The costs of this interactive video-counseling intervention are comparable with other retention in care or reengagement interventions.

BACKGROUND: We measured the immunogenicity of seasonal trivalent inactivated influenza vaccines (IIV3) among older Thai adults and the effect of one-year prior vaccination status on immune responses. METHOD: Adults aged ≥65 years (n = 370) were vaccinated with Southern Hemisphere IIV3 in 2015. Hemagglutination inhibition assays were performed using goose red blood cells on sera collected from the participants at baseline and after 1, 6, and 12 months of vaccination. Prior year vaccination (in 2014) was verified with the national health security office database. We analyzed the associations between prior vaccination and geometric mean titers (GMT) at each time point using generalized linear regression on logged transformed titers, and seroprotection and seroconversion using Log-binomial regression. RESULTS: At baseline, previously vaccinated participants (n = 203) had a significantly higher GMT and seroprotection against all three influenza strains than those previously unvaccinated (n = 167) (all p-values <0.001). Seroprotection rates were similar after one month in both groups for A(H1N1)pdm09 (adjusted risk ratio [aRR] 1.10, 95% CI 0.97-1.25), and A(H3N2) (aRR 1.08, 95% CI 0.87-1.33), but higher in previously vaccinated persons for B (aRR 1.20, 95% CI 1.08-1.32). At 12 months, 50% or more had seroprotection in previously vaccinated group with no difference between previously vaccinated or unvaccinated persons. Seroconversion was lower in the previously vaccinated group for A(H1N1)pdm09 (aRR 0.62, 95% CI 0.43-0.89), but did not differ between the two groups for A(H3N2) (aRR 0.94, 95% CI 0.69-1.28) and B (aRR 0.85, 95% CI 0.60-1.20). CONCLUSION: Influenza vaccination elicited good humoral response in older Thai adults. While seroconversion seemed attenuated in persons previously vaccinated for influenza A(H1N1)pdm09 (the only vaccine strain not to change), this was not apparent for influenza A(H3N2) and B, and prior vaccination was not associated with any inhibition in seroprotection.

INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.

INTRODUCTION: In 2019, an outbreak of e-cigarette, or vaping, product use-associated lung injury (EVALI) occurred in the US. We used Nielsen retail sales data to assess trends in sales of e-cigarettes, cigarettes, and nicotine replacement therapy (NRT) products before, during, and after the EVALI outbreak. METHODS: Monthly unit sales of e-cigarettes, cigarettes, and NRT products overall and by product type were assessed during January 2019 through June 2020 by using an interrupted time series model. Two time points were specified at the period ending July 13, 2019, and the period ending February 22, 2020, to partition before, during, and after the outbreak period. Sales trends by aggregated state-level EVALI case prevalence (low, medium, and high) were assessed to investigate interstate variations in changes of sales coinciding with the EVALI outbreak. RESULTS: Monthly e-cigarette sales increased 3.5% (P < .001) before the outbreak and decreased 3.1% (P < .001) during the outbreak, with no significant changes after the outbreak. Monthly cigarette sales increased 1.6% (P < .001) before the outbreak, decreased 1.8% (P < .001) during the outbreak, and increased 2.7% (P < .001) after the outbreak. NRT sales did not change significantly before or during the outbreak but decreased (2.8%, P = .01) after the outbreak. Sales trends by state-level EVALI case prevalence were similar to national-level sales trends. CONCLUSION: Cigarette and e-cigarette sales decreased during the EVALI outbreak, but no changes in overall NRT sales were observed until after the outbreak. Continued monitoring of tobacco sales data can provide insight into potential changes in use patterns and inform tobacco prevention and control efforts.

BACKGROUND: Although treatment and control of diabetes can prevent complications and reduce morbidity, few data sources exist at the state level for surveillance of diabetes comorbidities and control. Surveys and electronic health records (EHRs) offer different strengths and weaknesses for surveillance of diabetes and major metabolic comorbidities. Data from self-report surveys suffer from cognitive and recall biases, and generally cannot be used for surveillance of undiagnosed cases. EHR data are becoming more readily available, but pose particular challenges for population estimation since patients are not randomly selected, not everyone has the relevant biomarker measurements, and those included tend to cluster geographically. METHODS: We analyzed data from the National Health and Nutritional Examination Survey, the Health and Retirement Study, and EHR data from the DARTNet Institute to create state-level adjusted estimates of the prevalence and control of diabetes, and the prevalence and control of hypertension and high cholesterol in the diabetes population, age 50 and over for five states: Alabama, California, Florida, Louisiana, and Massachusetts. RESULTS: The estimates from the two surveys generally aligned well. The EHR data were consistent with the surveys for many measures, but yielded consistently lower estimates of undiagnosed diabetes prevalence, and identified somewhat fewer comorbidities in most states. CONCLUSIONS: Despite these limitations, EHRs may be a promising source for diabetes surveillance and assessment of control as the datasets are large and created during the routine delivery of health care. TRIAL REGISTRATION: Not applicable.

OBJECTIVE: Preexposure prophylaxis (PrEP) is recommended for people at risk of acquiring HIV. We assessed billable costs associated with PrEP delivery at community health centers. METHODS: The Sustainable Health Center Implementation PrEP Pilot (SHIPP) study is an observational cohort of people receiving daily oral PrEP at participating federally qualified health centers and other community health centers. We assessed health care utilization and billable costs of providing PrEP at 2 health centers, 1 in Chicago, Illinois, and 1 in Washington, DC, from 2014 to 2018. The health centers followed the clinical practice guidelines for PrEP provision, including regular visits with health care providers and ongoing laboratory monitoring. Using clinic billing records and Current Procedural Terminology (CPT) coding, we retrospectively extracted data on the frequency and costs (in 2017 US dollars) of PrEP clinic visits and laboratory screening, for each patient, for 12 months since first PrEP prescription. RESULTS: The average annual number of PrEP clinic visits and associated laboratory screens per patient was 5.1 visits and 25.2 screens in Chicago (n = 482 patients) and 5.4 visits and 24.8 screens in Washington, DC (n = 56 patients). The average annual PrEP billable cost per patient was $583 for clinic visits and $1070 for laboratory screens in Chicago and $923 for clinic visits and $1018 for laboratory screens in Washington, DC. The average annual total cost per patient was $1653 (95% CI, $1639-$1668) in Chicago and $1941 (95% CI, $1811-$2071) in Washington, DC. CONCLUSIONS: Our analysis, which provides PrEP billable cost estimates based on empirical data, may help inform health care providers who are considering implementing this HIV prevention strategy.

The degree to which individual heterogeneity in the production of secondary cases ("superspreading") affects tuberculosis (TB) transmission has not been systematically studied. We searched for population-based or surveillance studies in which whole genome sequencing was used to estimate TB transmission and the size distributions of putative TB transmission clusters were enumerated. We fit cluster size distribution data to a negative binomial branching process model to jointly infer the transmission parameters $R$ (the reproductive number) and dispersion parameter, $k$, which quantifies the propensity of superspreading in a population (generally, lower values of $k$ ($<1.0$) suggest increased heterogeneity). Of 4,796 citations identified in our initial search, nine studies met inclusion criteria ($n=5$ all TB; $n=4$ drug resistant TB) from eight global settings. Estimated $R$ values (range: 0.10, 0.73) were below 1.0, consistent with declining epidemics in the included settings; estimated $k$ values were well below 1.0 (range: 0.02, 0.48), indicating the presence of substantial individual-level heterogeneity in transmission across all settings. We estimated that a minority of cases (range 2-31%) drive the majority (80%) of ongoing transmission at the population level. Identifying sources of heterogeneity and accounting for them in TB control may have a considerable impact on mitigating TB transmission.

Surface water quality quantitative polymerase chain reaction (qPCR) technologies are expanding from a subject of research to routine environmental and public health laboratory testing. Readily available, reliable reference material is needed to interpret qPCR measurements, particularly across laboratories. Standard Reference Material® 2917 (NIST SRM® 2917) is a DNA plasmid construct that functions with multiple water quality qPCR assays allowing for estimation of total fecal pollution and identification of key fecal sources. This study investigates SRM 2917 interlaboratory performance based on repeated measures of 12 qPCR assays by 14 laboratories (n = 1008 instrument runs). Using a Bayesian approach, single-instrument run data are combined to generate assay-specific global calibration models allowing for characterization of within- and between-lab variability. Comparable data sets generated by two additional laboratories are used to assess new SRM 2917 data acceptance metrics. SRM 2917 allows for reproducible single-instrument run calibration models across laboratories, regardless of qPCR assay. In addition, global models offer multiple data acceptance metric options that future users can employ to minimize variability, improve comparability of data across laboratories, and increase confidence in qPCR measurements.

BACKGROUND: Between 2009 and 2019 opioid-involved fatal overdose rates increased by 45% and the average opioid dispensing rate in Wyoming was higher than the national average. The opioid crisis is shaped by a complex set of socioeconomic, geopolitical, and health-related variables. We conducted a vulnerability assessment to identify Wyoming counties at higher risk of opioid-related harm, factors associated with this risk, and areas in need of overdose treatment access to inform priority responses. METHODS: We compiled 2016 to 2018 county-level aggregated and de-identified data. We created risk maps and ran spatial analyses in a geographic information system to depict the spatial distribution of overdose-related measures. We used addresses of opioid treatment programs and buprenorphine providers to develop drive-time maps and ran 2-step floating catchment area analyses to measure accessibility to treatment. We used a straightforward and replicable weighted ranks approach to calculate final county vulnerability scores and rankings from most to least vulnerable. FINDINGS: We found Hot Springs, Carbon, Natrona, Fremont, and Sweetwater Counties to be most vulnerable to opioid-involved overdose fatalities. Opioid prescribing rates were highest in Hot Springs County (97 per 100 persons), almost two times the national average (51 per 100 persons). Statewide, there were over 90 buprenorphine-waivered providers, however accessibility to these clinicians was limited to urban centers. Most individuals lived further than a four-hour round-trip drive to the nearest methadone treatment program. CONCLUSIONS: Identifying Wyoming counties with high opioid overdose vulnerabilities and limited access to overdose treatment can inform public health and harm reduction responses.

INTRODUCTION: Information on morbidity-related productivity losses attributable to cigarette smoking, an important component of the economic burden of cigarette smoking, is limited. This study fills this gap by estimating these costs in the U.S. and by state. METHODS: A human capital approach was used to estimate the cost of the morbidity-related productivity losses (absenteeism, presenteeism, household productivity, and inability to work) attributable to cigarette smoking among adults aged 18 years in the U.S. and by state. A combination of data, including the 2014-2018 National Health Interview Survey, 2018 Current Population Survey Annual Social and Economic Supplement, 2018 Behavioral Risk Factor Surveillance System, 2018 value of daily housework, and literature-based estimate of lost productivity while at work (presenteeism), was used. Costs were estimated for 2018, and all analyses were conducted in 2021. RESULTS: Estimated total cost of morbidity-related productivity losses attributable to cigarette smoking in the U.S. in 2018 was $184.9 billion. Absenteeism, presenteeism, home productivity, and the inability to work accounted for $9.4 billion, $46.8 billion, $12.8 billion, and $116.0 billion, respectively. State-level total costs ranged from $291 million to $16.9 billion with a median cost of $2.7 billion. CONCLUSIONS: The cost of morbidity-related productivity losses attributable to cigarette smoking in the U.S. and in each state was substantial in 2018 and varied across the states. These estimates can guide public health policymakers and practitioners planning and evaluating interventions designed to alleviate the burden of cigarette smoking at the state and national levels.

Men who have sex with men (MSM) often change sexual behaviors following HIV diagnosis. This systematic review examined such changes, including sero-adaptive behaviors (i.e., deliberate safer-sex practices to reduce transmission risk) to better understand the magnitude of their association with HIV diagnosis. We searched four databases (1996-2017) and reviewed references from other systematic reviews. We included studies conducted in the United States that compared sexual behavior among HIV-infected "aware" versus "unaware" MSM. We meta-analytically pooled RRs and associated 95% confidence intervals (CI) using random-effects models, and assessed risk of bias and evidence quality. Twenty studies reported k = 131 effect sizes on sexual practices outcomes, most of which reported changes in unprotected sex (k = 85), and on sex with at-risk partners (k = 76); 11 reported sero-adaptive behaviors. Unprotected anal intercourse with an HIV-uninfected/unknown-status partner was less likely among aware MSM (insertive position: k = 2, RR 0.26, 95% CI 0.17, 0.41; receptive position: k = 2, RR 0.53, 95% CI 0.37, 0.77). Risk of not always serosorting among aware MSM (k = 3) was RR = 0.92 (0.83, 1.02). Existing evidence, although low-quality, suggests that HIV-infected MSM tend to adopt safer sexual practices once aware of their diagnosis. Variation in reporting of outcomes limits their comparability. Sero-adaptive behavior data are sparse.

BACKGROUND: Pneumococcal disease is a leading cause of bacterial pneumonia and invasive bacterial disease among children globally. The reason some strains of pneumococci are more likely to cause disease, and how interventions such as vaccines and antibiotics affect pneumococcal strains is poorly understood. We aimed to identify genetic regions under selective pressure and those associated with disease through the analysis of pneumococcal whole-genome sequences. METHODS: Whole-genome sequencing was performed on pneumococcal isolates collected between January, 2005, and May, 2018, in Kathmandu, Nepal, which included programmatic ten-valent pneumococcal conjugate vaccine (PCV10) introduction in 2015. Isolates were from three distinct cohorts: nasopharyngeal swabs of healthy community-based children, nasopharyngeal swabs of children admitted to hospital with pneumonia, and sterile-site cultures from children admitted to hospital. Across these cohorts we examined serotype distribution, antibiotic resistance, strain distribution, and regions of recombination to determine genes that were undergoing diversifying selection. Genome-wide association studies comparing pneumonia and sterile-site isolates with healthy carriage were used to determine novel variants associated with disease. FINDINGS: After programmatic introduction of PCV10, there was a decline in vaccine covered serotypes; however, strains that had expressed these serotypes continued to exist in the post-PCV population. We identified GPSC9 to be a strain of concern due to its high prevalence in disease, multidrug resistance, and ability to switch to an unencapsulated phenotype via insertion of virulence factor pspC into the cps locus. Antibiotic resistance loci to co-trimoxazole were found to be prevalent (pre-PCV10 78% vs post-PCV10 81%; p=0·27) and increasingly prevalent to penicillin (pre-PCV10 15% vs post-PCV10 32%; p<0·0001). Regions with multiple recombinations were identified spanning the surface protein virulence factors pspA and pspC and antibiotic targets pbpX, folA, folC, folE, and folP. Furthermore, we identified variants in lacE2 to be strongly associated with isolates from children with pneumonia and PRIP to be strongly associated with isolates from sterile sites. INTERPRETATION: Our work highlights the effect of pneumococcal conjugate vaccines, antibiotics, and host-pathogen interaction in pneumococcal variation, and the pathogen's capability of adapting to these factors at both population-wide and strain-specific levels. Ongoing surveillance of disease-associated strains and further investigation of lacE2 and PRIP as serotype-independent targets for therapeutic interventions is required. FUNDING: Gavi, The Vaccine Alliance; WHO; Bill & Melinda Gates Foundation; Wellcome Sanger Institute; and US Centers for Disease Control and Prevention.