OBJECTIVES: Assess the prevalence of current asthma, asthma attacks/episodes, and asthma-related emergency room (ER) visits by industry and occupation and estimate the proportion of current asthma cases associated with employment during 2020-2021. METHODS: The 2020-2021 National Health Interview Survey data for persons aged ≥18 years who were employed at any time during the 12 months prior to the interview were analyzed. RESULTS: An estimated 12.7 million US working adults had current asthma. Of those, 40% had an asthma attack/episode and 8.6% had an asthma-related ER visit. Prevalence varied by sociodemographic characteristics, industry, and occupation. Highest asthma prevalence was among workers in the administrative, support, waste management, and remediation industry and the community and social services occupation. Nearly half of workers with current asthma in the arts, entertainment, and recreation industry and arts, design, entertainment, sports, and media occupations reported having an asthma attack/episode. Workers in the accommodations and food services industry and food preparation and serving related occupation had the highest asthma-related ER visits. The proportion of current asthma cases attributable to employment was estimated to be 9.2% by industry and 12.2% by occupation. CONCLUSION: An estimated 1.2-1.5 million asthma cases among workers might be attributable to employment by industry and occupation. Disparities in asthma prevalence, asthma attacks/episodes and asthma-related ER visits among workers exist. These findings underscore the importance of early identification of asthma cases in relation to work and implementation of targeted interventions (including, training and education, personal protective equipment use, health surveillance, workplace policies), especially among workers employed in industries and occupations with elevated asthma prevalence.

BACKGROUND: Asthma, a chronic respiratory disease, is associated with high economic burden. This study estimates per-worker medical and incremental medical costs associated with treated asthma by socioeconomic and demographic characteristics, industries, medical events, and sources of payments for workers aged ≥18 years. METHODS: We analyzed Medical Expenditure Panel Survey data from 2018 to 2020 to assess medical costs for treated asthma among workers using the International Classification of Diseases, Tenth Revision, Clinical Modification code for asthma (J45). We used two-part regression models to estimate medical and incremental medical costs controlling for covariates. All results are adjusted for inflation and presented in 2022 US dollar values. RESULTS: An estimated annual average of 8.2 million workers out of 176 million had at least one medical event associated with treated asthma. The annualized estimated per-worker incremental medical costs for those with treated asthma was $457 and was highest among: those in the age group of 35-44 years ($534), in the western region ($768), of Hispanic ethnicity ($693), employed in the utility and transportation industries ($898), males ($650), and for inpatient admissions ($754). The total annualized medical costs of treated asthma was $21 billion and total of incremental medical costs was $3.8 billion. CONCLUSION: Findings of higher incremental medical costs for treated asthma among workers in certain socioeconomic, demographic, and industry groups highlight the economic benefit of prevention and early intervention to reduce morbidity of asthma in working adults. Our results suggest that the per-person incremental medical costs of treated asthma among workers are lower than that for all US adults.

BACKGROUND: Although antivirals remain important for the treatment COVID-19, methods to assess treatment efficacy are lacking. Here, we investigated the impact of remdesivir on viral dynamics and their contribution to understanding antiviral efficacy in the multicenter ACTT-1 clinical trial that randomized patients to remdesivir or placebo. METHODS: Longitudinal specimens collected during hospitalization from a substudy of 642 COVID-19 patients were measured for viral RNA (upper respiratory tract and plasma), viral nucleocapsid antigen (serum), and host immunologic markers. Associations with clinical outcomes and response to therapy were assessed. RESULTS: Higher baseline plasma viral loads were associated with poorer clinical outcomes, and decreases in viral RNA and antigen in blood but not the upper respiratory tract correlated with enhanced benefit from remdesivir. The treatment effect of remdesivir was most pronounced in patients with elevated baseline nucleocapsid antigen levels: the recovery rate ratio was 1.95 (95%CI 1.40-2.71) for levels >245 pg/ml vs 1.04 (95%CI 0.76-1.42) for levels < 245 pg/ml. Remdesivir also accelerated the rate of viral RNA and antigen clearance in blood, and patients whose blood levels decreased were more likely to recover and survive. CONCLUSIONS: Reductions in SARS-CoV-2 RNA and antigen levels in blood correlated with clinical benefit from antiviral therapy.

BACKGROUND: For many years, there has been concern about the risk of transmission of classic forms of Creutzfeldt-Jakob disease (CJD) by blood transfusion, particularly after the recognition of such transmission of variant CJD (vCJD). We report on a 28-year lookback study of recipients of blood from donors who subsequently developed CJD. METHODS: Patients with diagnosed CJD and a history of blood donation were identified. Blood centers were asked to provide information about the distribution of the donations and consignees were requested to provide information about the recipients of the donations. Vital status of each available recipient was determined and, if deceased, the reported cause(s) of death were obtained primarily from the National Death Index. All recipients included in the study database contributed person-time up to the last recorded review of vital status. RESULTS: There were 84 eligible donors who gave 3284 transfusable components, and it was possible to evaluate 1245 recipients, totaling 6495 person-years of observation. The mean observation period per recipient was 5.5 years with a maximum of 51 years. No case of CJD or prion disease was reported among the recipient population. DISCUSSION: The study suggests that CJD may not be transfusion-transmissible, a position in agreement with similar findings from two similar European reports amounting to an overall observation period of 15,500 person-years. These studies have supported the conclusion that the risk, if any, of transmission of CJD by blood products is extremely small and remains theoretical.

BACKGROUND: Work-related asthma (WRA), a preventable occupational disease, can result in adverse health outcomes and employment disability, including decreased productivity, lost workdays, and job loss. Early identification of WRA cases and avoidance of further exposures is crucial for optimal management. OBJECTIVE: We estimate WRA prevalence among US workers by selected sociodemographic characteristics, industry, and occupation groups and assess the differences in adverse health outcomes, preventive care, and lost workdays between persons with WRA and those with non-WRA. METHODS: The 2020 National Health Interview Survey (NHIS) data for working adults aged ≥18 years employed in the 12 months before the survey were analyzed. Prevalence, and adjusted prevalence ratios with 95% confidence intervals were estimated using multivariate logistic regression. RESULTS: Of the estimated 170 million US adults working in the past year, 13.0 million (7.6%) had asthma. Among workers with asthma, an estimated 896,000 (6.9%) had WRA. WRA prevalence was highest among males, workers aged ≥55 years, those with no health insurance, those living in the Midwest, and those employed in the accommodation, food, and other services industry, and in production, installation, transportation, and material moving occupations. Workers with WRA were significantly more likely to use preventive medication and rescue inhalers, and to experience adverse health outcomes and lost workdays than workers with non-WRA. CONCLUSION: Early identification of WRA cases, assessment of workplace exposures, and implementation of targeted interventions that consider the hierarchy of controls are critical to preventing future WRA cases and associated adverse health consequences.

BACKGROUND: Inhalation injuries due to acute occupational exposures to chemicals are preventable. National surveillance of acute inhalation exposures is limited. This study identified the most common acute inhalation exposure-related incidents by industry sector among US workers. METHODS: To characterize inhalation-related injuries and their exposures during April 2011-March 2022, state and federal records from the Occupational Safety and Health Administration (OSHA) Occupational Safety and Health Information System (OIS) accident database were analyzed. Industry-specific injury, hospitalization, and fatality rates were calculated. RESULTS: The most frequent acute inhalation incidents investigated by OSHA were caused by inorganic gases (52.9%) such as carbon monoxide (CO) or acids, bases, and oxidizing chemical agents (12.9%) such as anhydrous ammonia. The largest number of fatal and nonfatal injuries were reported in the manufacturing (28.6%) and construction (17.2%) sectors. CONCLUSIONS: Workers were affected by acute inhalation exposures in most industries. Using this surveillance, employers can recognize frequently-occurring preventable acute inhalation exposures by industry, such as inorganic gases in the manufacturing sector, and implement prevention measures. Training of workers on exposure characteristics and limits, adverse health effects, and use of protective equipment by exposure agent can prevent inhalation injuries.

Marburg virus (MARV) and Ravn virus (RAVV), collectively called marburgviruses, cause Marburg hemorrhagic fever (MHF) in humans. In July 2007, 4 cases of MHF (1 fatal) occurred in miners at Kitaka Mine in southern Uganda. Later, MHF occurred in 2 tourists who visited Python Cave, ≈50 km from Kitaka Mine. One of the tourists was from the United States (December 2007) and 1 was from the Netherlands (July 2008); 1 case was fatal (1,2,3). The cave and the mine each contained 40,000–100,000 Rousettus aegyptiacus bats (Egyptian fruit bats). | | Longitudinal investigations of the outbreaks at both locations were initiated by the Viral Special Pathogens Branch of the Centers for Disease Control and Prevention (CDC, Atlanta, GA, USA, and Entebbe, Uganda) in collaboration with the Uganda Wildlife Authority (UWA) and the Uganda Virus Research Institute (UVRI). During these studies, genetically diverse MARVs and RAVVs were isolated directly from bat tissues, and infection levels of the 2 viruses were found to increase in juvenile bats on a predictable bi-annual basis (4,5). However, investigations at Kitaka Mine were stopped when the miners exterminated the bat colony by restricting egress from the cave with papyrus reed barriers and then entangling the bats in fishing nets draped over the exits. The trapping continued for weeks, and the entrances were then sealed with sticks and plastic. These depopulation efforts were documented by researchers from UVRI, the CDC, the National Institute of Communicable Diseases (Sandringham, South Africa), and UWA during site visits to Kitaka Mine (Technical Appendix Figure). In August 2008, thousands of dead bats were found piled in the forest, and by November 2008, there was no evidence of bats living in the mine; whether 100% extermination was achieved is unknown. CDC, UVRI, and UWA recommended against extermination, believing that any results would be temporary and that such efforts could exacerbate the problem if bat exclusion methods were not complete and permanent (6,7).

BACKGROUND: The efficacy of daily co-trimoxazole, an antifolate used for malaria chemoprevention in pregnant women living with HIV, is threatened by cross-resistance of Plasmodium falciparum to the antifolate sulfadoxine-pyrimethamine. We assessed whether addition of monthly dihydroartemisinin-piperaquine to daily co-trimoxazole is more effective at preventing malaria infection than monthly placebo plus daily co-trimoxazole in pregnant women living with HIV. METHODS: We did an individually randomised, two-arm, placebo-controlled trial in areas with high-grade sulfadoxine-pyrimethamine resistance in Kenya and Malawi. Pregnant women living with HIV on dolutegravir-based combination antiretroviral therapy (cART) who had singleton pregnancies between 16 weeks' and 28 weeks' gestation were randomly assigned (1:1) by computer-generated block randomisation, stratified by site and HIV status (known positive vs newly diagnosed), to daily co-trimoxazole plus monthly dihydroartemisinin-piperaquine (three tablets of 40 mg dihydroartemisinin and 320 mg piperaquine given daily for 3 days) or daily co-trimoxazole plus monthly placebo. Daily co-trimoxazole consisted of one tablet of 160 mg sulfamethoxazole and 800 mg trimethoprim. The primary endpoint was the incidence of Plasmodium infection detected in the peripheral (maternal) or placental (maternal) blood or tissue by PCR, microscopy, rapid diagnostic test, or placental histology (active infection) from 2 weeks after the first dose of dihydroartemisinin-piperaquine or placebo to delivery. Log-binomial regression was used for binary outcomes, and Poisson regression for count outcomes. The primary analysis was by modified intention to treat, consisting of all randomised eligible participants with primary endpoint data. The safety analysis included all women who received at least one dose of study drug. All investigators, laboratory staff, data analysts, and participants were masked to treatment assignment. This trial is registered with ClinicalTrials.gov, NCT04158713. FINDINGS: From Nov 11, 2019, to Aug 3, 2021, 904 women were enrolled and randomly assigned to co-trimoxazole plus dihydroartemisinin-piperaquine (n=448) or co-trimoxazole plus placebo (n=456), of whom 895 (99%) contributed to the primary analysis (co-trimoxazole plus dihydroartemisinin-piperaquine, n=443; co-trimoxazole plus placebo, n=452). The cumulative risk of any malaria infection during pregnancy or delivery was lower in the co-trimoxazole plus dihydroartemisinin-piperaquine group than in the co-trimoxazole plus placebo group (31 [7%] of 443 women vs 70 [15%] of 452 women, risk ratio 0·45, 95% CI 0·30-0·67; p=0·0001). The incidence of any malaria infection during pregnancy or delivery was 25·4 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 77·3 per 100 person-years in the co-trimoxazole plus placebo group (incidence rate ratio 0·32, 95% CI 0·22-0·47, p<0·0001). The number needed to treat to avert one malaria infection per pregnancy was 7 (95% CI 5-10). The incidence of serious adverse events was similar between groups in mothers (17·7 per 100 person-years in the co-trimoxazole plus dihydroartemisinin-piperaquine group [23 events] vs 17·8 per 100 person-years in the co-trimoxazole group [25 events]) and infants (45·4 per 100 person-years [23 events] vs 40·2 per 100 person-years [21 events]). Nausea within the first 4 days after the start of treatment was reported by 29 (7%) of 446 women in the co-trimoxazole plus dihydroartemisinin-piperaquine group versus 12 (3%) of 445 women in the co-trimoxazole plus placebo group. The risk of adverse pregnancy outcomes did not differ between groups. INTERPRETATION: Addition of monthly intermittent preventive treatment with dihydroartemisinin-piperaquine to the standard of care with daily unsupervised co-trimoxazole in areas of high antifolate resistance substantially improves malaria chemoprevention in pregnant women living with HIV on dolutegravir-based cART and should be considered for policy. FUNDING: European and Developing Countries Clinical Trials Partnership 2; UK Joint Global Health Trials Scheme (UK Foreign, Commonwealth and Development Office; Medical Research Council; National Institute for Health Research; Wellcome); and Swedish International Development Cooperation Agency.

The tragedy of transfusion-associated hepatitis and HIV spurred a decades-long overhaul of the regulatory oversight and practice of blood transfusion. Consequent to improved donor selection, testing, process control, clinical transfusion practice and post-transfusion surveillance, transfusion in the United States and other high-income countries is now a very safe medical procedure. Nonetheless, pathogens continue to emerge and threaten the blood supply, highlighting the need for a proactive approach to blood transfusion safety. Blood donor populations and the global transfusion infrastructure are under-utilized resources for the study of infectious diseases. Blood donors are large, demographically diverse subsets of general populations for whom cross-sectional and longitudinal samples are readily accessible for serological and molecular testing. Blood donor collection networks span diverse geographies, including in low- and middle-income countries, where agents, especially zoonotic pathogens, are able to emerge and spread, given limited tools for recognition, surveillance and control. Routine laboratory storage and transportation, coupled with data capture, afford access to rich epidemiological data to assess the epidemiology and pathogenesis of established and emerging infections. Subsequent to the State of the Science in Transfusion Medicine symposium in 2022, our working group (WG), "Emerging Infections: Impact on Blood Science, the Blood Supply, Blood Safety, and Public Health" elected to focus on "leveraging donor populations to study the epidemiology and pathogenesis of transfusion-transmitted and emerging infectious diseases." The 5 landmark studies span (1) the implication of hepatitis C virus in post-transfusion hepatitis, (2) longitudinal evaluation of plasma donors with incident infections, thus informing the development of a widely used staging system for acute HIV infection, (3) explication of the dynamics of early West Nile Virus infection, (4) the deployment of combined molecular and serological donor screening for Babesia microti, to characterize its epidemiology and infectivity and facilitate routine donor screening, and (5) national serosurveillance for SARS-CoV-2 during the COVID-19 pandemic. The studies highlight the interplay between infectious diseases and transfusion medicine, including the imperative to ensure blood transfusion safety and the broader application of blood donor populations to the study of infectious diseases.

INTRODUCTION: The Coronavirus Disease 2019 (COVID-19) pandemic has disproportionately impacted workers in certain industries and occupations. The infection risk for SARS-CoV-2 and future respiratory viruses in the workplace is a significant concern for workers, employers, and policymakers. The current study describes the differences in COVID-19 mortality by sex and industry/occupation among working-age U.S. residents in 49 states and New York City. METHODS: The 2021 National Vital Statistics System (NVSS) public use multiple-cause-of-death data for U.S. decedents aged 15‒64 years (working-age) with information on usual industry and occupation were analyzed in 2022. Age-standardized COVID-19 death rates for selected demographic characteristics and adjusted proportional mortality ratios (PMRs) were estimated by sex and by usual industry and occupation. RESULTS: In 2021, 133,596 (14.3%) U.S. decedents aged 15‒64 years had COVID-19 listed as the underlying cause of death; the highest COVID-19 death rate was among persons aged 55‒64 years (172.4/100,000 population) and males (65.5/100,000 population). Among males, American Indian or Alaskan Native and among females, Black or African American had the highest death rates. Hispanic males had higher age-adjusted death rates than Hispanic females. Working-age male decedents in the public administration (PMR=1.39) and management of companies & enterprises industries (PMR=1.39) and community and social services occupations (PMR=1.68) and female decedents in the utilities industry (PMR=1.20) and protective services occupation (PMR=1.18) had the highest PMRs. CONCLUSIONS: COVID-19 death rates and PMRs varied by sex, industry, and occupation groups. These findings underscore the importance of workplace public health interventions, which could protect workers and their communities.

OBJECTIVE: Malaria and sexually transmitted and reproductive tract infections (STIs/RTIs) are highly prevalent in sub-Saharan Africa and associated with poor pregnancy outcomes. We investigated the individual and combined effects of malaria and curable STIs/RTIs on fetal growth in Kenya, Tanzania, and Malawi. METHODS: This study was nested within a randomized trial comparing monthly intermittent preventive treatment for malaria in pregnancy with sulfadoxine-pyrimethamine versus dihydroartemisinin-piperaquine, alone or combined with azithromycin. Fetal weight gain was assessed by serial prenatal ultrasound. Malaria was assessed monthly, and Treponema pallidum, Neisseria gonorrhoeae, Trichomonas vaginalis, Chlamydia trachomatis and bacterial vaginosis at enrolment and in the third trimester. The effect of malaria and STIs/RTIs on fetal weight/birthweight Z-scores was evaluated using mixed-effects linear regression. RESULTS: 1,435 pregnant women had fetal/birth weight assessed 3,950 times. Compared to women without malaria or STIs/RTIs (n=399), malaria-only (n=267), STIs/RTIs-only (n=410) or both (n=353) were associated with reduced fetal growth (adjusted mean difference in fetal/birth weight Z-score [95% CI]: malaria=-0.18 [-0.31,-0.04], p=0.01]; STIs/RTIs=-0.14 [-0.26,-0.03], p=0.01]; both=-0.20 [-0.33,-0.07], p=0.003). Paucigravidae experienced the greatest impact. CONCLUSION: Malaria and STIs/RTIs are associated with poor fetal growth especially among paucigravidae women with dual infections. Integrated antenatal interventions are needed to reduce the burden of both malaria and STIs/RTIs.

BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

BACKGROUND: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. METHODS: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. RESULTS: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. CONCLUSIONS: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious. METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only. RESULTS: A total of 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%). CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with dihydroartemisinin-piperaquine is more effective than IPTp with sulfadoxine-pyrimethamine at reducing malaria infection during pregnancy in areas with high-grade resistance to sulfadoxine-pyrimethamine by Plasmodium falciparum in east Africa. We aimed to assess whether IPTp with dihydroartemisinin-piperaquine, alone or combined with azithromycin, can reduce adverse pregnancy outcomes compared with IPTp with sulfadoxine-pyrimethamine. METHODS: We did an individually randomised, double-blind, three-arm, partly placebo-controlled trial in areas of high sulfadoxine-pyrimethamine resistance in Kenya, Malawi, and Tanzania. HIV-negative women with a viable singleton pregnancy were randomly assigned (1:1:1) by computer-generated block randomisation, stratified by site and gravidity, to receive monthly IPTp with sulfadoxine-pyrimethamine (500 mg of sulfadoxine and 25 mg of pyrimethamine for 1 day), monthly IPTp with dihydroartemisinin-piperaquine (dosed by weight; three to five tablets containing 40 mg of dihydroartemisinin and 320 mg of piperaquine once daily for 3 consecutive days) plus a single treatment course of placebo, or monthly IPTp with dihydroartemisinin-piperaquine plus a single treatment course of azithromycin (two tablets containing 500 mg once daily for 2 consecutive days). Outcome assessors in the delivery units were masked to treatment group. The composite primary endpoint was adverse pregnancy outcome, defined as fetal loss, adverse newborn baby outcomes (small for gestational age, low birthweight, or preterm), or neonatal death. The primary analysis was by modified intention to treat, consisting of all randomised participants with primary endpoint data. Women who received at least one dose of study drug were included in the safety analyses. This trial is registered with ClinicalTrials.gov, NCT03208179. FINDINGS: From March-29, 2018, to July 5, 2019, 4680 women (mean age 25·0 years [SD 6·0]) were enrolled and randomly assigned: 1561 (33%; mean age 24·9 years [SD 6·1]) to the sulfadoxine-pyrimethamine group, 1561 (33%; mean age 25·1 years [6·1]) to the dihydroartemisinin-piperaquine group, and 1558 (33%; mean age 24·9 years [6.0]) to the dihydroartemisinin-piperaquine plus azithromycin group. Compared with 335 (23·3%) of 1435 women in the sulfadoxine-pyrimethamine group, the primary composite endpoint of adverse pregnancy outcomes was reported more frequently in the dihydroartemisinin-piperaquine group (403 [27·9%] of 1442; risk ratio 1·20, 95% CI 1·06-1·36; p=0·0040) and in the dihydroartemisinin-piperaquine plus azithromycin group (396 [27·6%] of 1433; 1·16, 1·03-1·32; p=0·017). The incidence of serious adverse events was similar in mothers (sulfadoxine-pyrimethamine group 17·7 per 100 person-years, dihydroartemisinin-piperaquine group 14·8 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 16·9 per 100 person-years) and infants (sulfadoxine-pyrimethamine group 49·2 per 100 person-years, dihydroartemisinin-piperaquine group 42·4 per 100 person-years, and dihydroartemisinin-piperaquine plus azithromycin group 47·8 per 100 person-years) across treatment groups. 12 (0·2%) of 6685 sulfadoxine-pyrimethamine, 19 (0·3%) of 7014 dihydroartemisinin-piperaquine, and 23 (0·3%) of 6849 dihydroartemisinin-piperaquine plus azithromycin treatment courses were vomited within 30 min. INTERPRETATION: Monthly IPTp with dihydroartemisinin-piperaquine did not improve pregnancy outcomes, and the addition of a single course of azithromycin did not enhance the effect of monthly IPTp with dihydroartemisinin-piperaquine. Trials that combine sulfadoxine-pyrimethamine and dihydroartemisinin-piperaquine for IPTp should be considered. FUNDING: European & Developing Countries Clinical Trials Partnership 2, supported by the EU, and the UK Joint-Global-Health-Trials-Scheme of the Foreign, Commonwealth and Development Office, Medical Research Council, Department of Health and Social Care, Wellcome, and the Bill-&-Melinda-Gates-Foundation.

We discuss the experience of some Pacific island countries in introducing the new WHO-recommended treatment protocol for lymphatic filariasis-a triple-drug therapy composed of ivermectin, diethylcarbamazine, and albendazole. The successful rollout of the new treatment protocol was dependent on strong partnerships among these countries' ministries of health, WHO, and other stakeholders. Effective communication among these partners allowed for lessons learned to cross borders and have a positive impact on the experiences of other countries. We also describe various challenges confronted during this process and the ways these countries overcame them.

Chronic obstructive pulmonary disease (COPD), a progressive lung disease, is characterized by long-term respiratory symptoms and airflow limitation (1). COPD accounts for most of the deaths from chronic lower respiratory diseases, the sixth leading cause of death in the United States in 2020.* Workplace exposures and tobacco smoking are risk factors for COPD; however, one in four workers with COPD have never smoked (2-4). To describe COPD mortality among U.S. residents aged 15 years categorized as ever-employed (i.e., with information on their usual industry and occupation), CDC analyzed the most recent 2020 multiple cause-of-death data() from 46 states and New York City.() Among 3,077,127 decedents, 316,023 (10.3%) had COPD() listed on the death certificate. The highest age-adjusted** COPD death rates per 100,000 ever-employed persons were for females (101.3), White persons (116.9), and non-Hispanic or Latino (non-Hispanic) persons (115.8). The highest proportionate mortality ratios (PMRs)() were for workers employed in the mining industry (1.3) and in food preparation and serving related occupations (1.3). Elevated COPD mortality among workers in certain industries and occupations underscores the importance of targeted interventions (e.g., reduction or elimination of COPD-associated risk factors, engineering controls, and workplace smoke-free policies) to prevent COPD from developing and to intervene before illness becomes symptomatic or severe.

INTRODUCTION: Asthma is associated with an increased risk for cardiovascular disease, and adults with persistent, severe asthma have a significantly higher risk of cardiovascular disease than adults with intermittent or no asthma. METHODS: The objective of this cross-sectional study was to assess the association between work-related asthma status and cardiovascular disease among ever-employed adults (aged 18-64 years) with current asthma using data from the 2012-2017 Behavioral Risk Factor Surveillance System Asthma Call-Back Survey from 37 states and the District of Columbia. Weighted prevalence ratios and 95% CIs, adjusted for age, sex, race/ethnicity, education, household income, smoking status, chronic obstructive pulmonary disease, diabetes, and BMI, were calculated. In addition, the associations of cardiovascular disease with adverse asthma outcomes and asthma control among adults with work-related asthma were examined. Analyses were conducted in 2021. RESULTS: Among an estimated annualized 14.8 million ever-employed adults aged 18-64 years with current asthma, adults with work-related asthma (prevalence ratio=1.5; 95% CI=1.2, 1.8) and possible work-related asthma (prevalence ratio=1.2; 95% CI=1.0, 1.5) were significantly more likely to have cardiovascular disease than adults with non-work-related asthma. Among adults with work-related asthma, those with very poorly controlled asthma (prevalence ratio=1.8; 95% CI=1.3, 2.5) and an asthma-related emergency room visit (prevalence ratio=1.5; 95% CI=1.1, 2.0) were significantly more likely to have cardiovascular disease. CONCLUSIONS: Adults with work-related asthma were more likely to have cardiovascular disease than those with non-work-related asthma. Primary prevention, early diagnosis, and implementation of optimal work-related asthma management are essential for workers' health. Cardiovascular disease should be considered where appropriate when diagnosing and recommending treatment and interventions for adults with work-related asthma.

BACKGROUND: Asthma-COPD overlap (ACO) is a respiratory condition with more severe respiratory symptoms, poorer quality of life, and increased hospital admissions compared with asthma or COPD alone. OBJECTIVES: Estimate asthma, chronic obstructive pulmonary disease (COPD), and ACO prevalence among workers by industry and occupation and assess physical and mental health status, healthcare utilization, among workers with ACO. METHODS: The 2014-2018 National Health Interview Survey (NHIS) data for working adults aged ≥18 years employed (sample n = 99,424) in the 12 months prior to the survey were analyzed. Age-adjusted ACO, COPD and asthma prevalence and prevalence ratios adjusted for age, sex, race and smoking status were estimated. RESULTS: During 2014-2018, of the estimated 166 million (annual average) US workers, age-adjusted asthma, COPD, and ACO prevalence was 6.9%, 4.0%, and 1.1%, respectively. ACO prevalence was highest among workers aged ≥65 years (2.0%), females (1.6%), current smokers (1.9%), those living below the federal poverty level (2.3%), and workers in the accommodation and food services (1.6%) industry and personal care and service (2.3%) occupations. Workers with ACO had more frequent (p < 0.05) physician office visits, emergency department visits; and were more likely to be in poorer mental health, obese, have more lost workdays, more bed days, and comorbidities compared to workers with asthma alone and workers with COPD alone.Conclusion: Higher ACO prevalence among worker groups and increased healthcare utilization underscores the need for early identification of asthma and COPD, assessment of potential workplace exposures, and implementation of tailored interventions to reduce ACO among working adults.

With advances in nanotechnology, engineered nanomaterial applications are a rapidly growing sector of the economy. Some nanomaterials can reach the brain through nose-to-brain transport. This transport creates concern for potential neurotoxicity of insoluble nanomaterials and a need for toxicity screening tests that detect nose-to-brain transport. Such tests can involve intranasal instillation of aqueous suspensions of nanomaterials in dispersion media that limit particle agglomeration. Unfortunately, protein and some elements in existing dispersion media are suboptimal for potential nose-to-brain transport of nanomaterials because olfactory transport has size- and ion-composition requirements. Therefore, we designed a protein-free dispersion media containing phospholipids and amino acids in an isotonic balanced electrolyte solution, a solution for nasal and olfactory transport (SNOT). SNOT disperses hexagonal boron nitride nanomaterials with a peak particle diameter below 100 nm. In addition, multiwalled carbon nanotubes (MWCNTs) in an established dispersion medium, when diluted with SNOT, maintain dispersion with reduced albumin concentration. Using stereomicroscopy and microscopic examination of plastic sections, dextran dyes dispersed in SNOT are demonstrated in the neuroepithelium of the nose and olfactory bulb of B6;129P2-Omp(tm3Mom)/MomJ mice after intranasal instillation in SNOT. These findings support the potential for SNOT to disperse nanomaterials in a manner permitting nose-to-brain transport for neurotoxicity studies.

BACKGROUND: Multi-walled carbon nanotubes and nanofibers (CNT/F) have been previously investigated for their potential toxicities; however, comparative studies of the broad material class are lacking, especially those with a larger diameter. Additionally, computational modeling correlating physicochemical characteristics and toxicity outcomes have been infrequently employed, and it is unclear if all CNT/F confer similar toxicity, including histopathology changes such as pulmonary fibrosis. Male C57BL/6 mice were exposed to 40 µg of one of nine CNT/F (MW #1-7 and CNF #1-2) commonly found in exposure assessment studies of U.S. facilities with diameters ranging from 6 to 150 nm. Human fibroblasts (0-20 µg/ml) were used to assess the predictive value of in vitro to in vivo modeling systems. RESULTS: All materials induced histopathology changes, although the types and magnitude of the changes varied. In general, the larger diameter MWs (MW #5-7, including Mitsui-7) and CNF #1 induced greater histopathology changes compared to MW #1 and #3 while MW #4 and CNF #2 were intermediate in effect. Differences in individual alveolar or bronchiolar outcomes and severity correlated with physical dimensions and how the materials agglomerated. Human fibroblast monocultures were found to be insufficient to fully replicate in vivo fibrosis outcomes suggesting in vitro predictive potential depends upon more advanced cell culture in vitro models. Pleural penetrations were observed more consistently in CNT/F with larger lengths and diameters. CONCLUSION: Physicochemical characteristics, notably nominal CNT/F dimension and agglomerate size, predicted histopathologic changes and enabled grouping of materials by their toxicity profiles. Particles of greater nominal tube length were generally associated with increased severity of histopathology outcomes. Larger particle lengths and agglomerates were associated with more severe bronchi/bronchiolar outcomes. Spherical agglomerated particles of smaller nominal tube dimension were linked to granulomatous inflammation while a mixture of smaller and larger dimensional CNT/F resulted in more severe alveolar injury.

Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1).

Asthma and chronic obstructive pulmonary disease (COPD) are respiratory conditions associated with a significant economic cost among U.S. adults (1,2), and up to 44% of asthma and 50% of COPD cases among adults are associated with workplace exposures (3). CDC analyzed 2011-2015 Medical Expenditure Panel Survey (MEPS) data to determine the medical expenditures attributed to treatment of asthma and COPD among U.S. workers aged >/=18 years who were employed at any time during the survey year. During 2011-2015, among the estimated 166 million U.S. workers, 8 million had at least one asthma-related medical event,* and 7 million had at least one COPD-related medical event. The annualized total medical expenditures, in 2017 dollars, were $7 billion for asthma and $5 billion for COPD. Private health insurance paid for 61% of expenditures attributable to treatment of asthma and 59% related to COPD. By type of medical event, the highest annualized per-person asthma- and COPD-related expenditures were for inpatient visits: $8,238 for asthma and $27,597 for COPD. By industry group, the highest annualized per-person expenditures ($1,279 for asthma and $1,819 for COPD) were among workers in public administration. Early identification and reduction of risk factors, including workplace exposures, and implementation of proven interventions are needed to reduce the adverse health and economic impacts of asthma and COPD among workers.

Patients with asthma typically have chronic airway inflammation, variable airflow limitation, and intermittent respiratory symptoms; patients with chronic obstructive pulmonary disease (COPD) often have fixed airflow limitation and persistent respiratory symptoms. Some patients exhibit features suggesting that they have both conditions, which is termed asthma-COPD overlap. These patients have been reported to have worse health outcomes than do those with asthma or COPD alone (1). To describe mortality among persons aged >/=25 years with asthma-COPD overlap, CDC analyzed 1999-2016 National Vital Statistics multiple-cause-of-death mortality data* extracted from the National Occupational Mortality System (NOMS), which included industry and occupation(dagger) information collected from 26 states( section sign) for the years 1999, 2003, 2004, and 2007-2014. Age-adjusted death rates per one million persons( paragraph sign) and proportionate mortality ratios (PMRs)** were calculated. During 1999-2016, 6,738 male decedents (age-adjusted rate per million = 4.30) and 12,028 female decedents (5.59) had both asthma and COPD assigned on their death certificate as the underlying or contributing cause of death. The annual age-adjusted death rate per million among decedents with asthma-COPD overlap declined from 6.70 in 1999 to 3.01 in 2016 (p<0.05) for men and from 7.71 in 1999 to 4.01 in 2016 (p<0.05) for women. Among adults aged 25-64 years, asthma-COPD overlap PMRs, by industry, were significantly elevated among nonpaid workers, nonworkers, and persons working at home for both men (1.72) and women (1.40) and among male food, beverage, and tobacco products workers (2.64). By occupation, asthma-COPD overlap PMRs were significantly elevated among both men (1.98) and women (1.79) who were unemployed, had never worked, or were disabled workers and among women bartenders (3.28) and homemakers (1.34). The association between asthma-COPD overlap mortality and nonworking status among adults aged 25-64 years suggests that asthma-COPD overlap might be associated with substantial morbidity. Increased risk for asthma-COPD overlap mortality among adults in certain industries and occupations suggests targets for public health interventions (e.g., elimination of or removal from exposures, engineering controls, and workplace smoke-free policies) to prevent asthma and COPD in and out of the workplace.

Lymphatic filariasis is a debilitating and disfiguring mosquitoborne parasitic disease. As part of the Global Programme to Eliminate Lymphatic Filariasis, the World Health Organization (WHO) recommends at least five rounds of annual mass drug administration (MDA) in areas with endemic disease to reduce incidence and prevalence (1). Onward transmission is expected to end once community prevalence falls below 1% (1). | | American Samoa, located in the southern Pacific Ocean, is the only U.S. territory with evidence of ongoing lymphatic filariasis transmission. After 7 years of MDA (2000–2006), the prevalence of lymphatic filariasis antigenemia in American Samoa declined from 16.5% to 2.3%, and MDA was stopped (2,3). In 2016, a household survey among 2,507 participants revealed that the prevalence of antigenemia had rebounded to 6.2%, and transmission was ascertained to be widespread across the territory (4). MDA was resumed in 2018 using a novel three-drug regimen of ivermectin, diethylcarbamazine, and albendazole, which has been shown to more effectively clear filarial larvae from the blood than the standard two-drug treatment of albendazole with diethylcarbamazine or ivermectin alone (5,6). This WHO-recommended three-drug regimen is anticipated to accelerate progress toward global elimination goals in areas without other filarial infections that would contraindicate the use of diethylcarbamazine (onchocerciasis) or ivermectin (loiasis).

OBJECTIVE: To describe the frequency of work-related asthma (WRA) and characteristics of individuals with exposure to cleaning products 1998-2012, compared to 1993-1997. METHODS: Cases of WRA from products used for cleaning or disinfecting surfaces were identified from California, Massachusetts, Michigan (1998-2012), New Jersey (1998-2011), and New York (2009-2012). RESULTS: There were 1,199 (12.4%) cleaning product cases among all 9,667 WRA cases; 77.8% women, 62.1% white non-Hispanic, and average age of 43 years. The highest percentage worked in healthcare (41.1%), and were building cleaners (20.3%), or registered nurses (14.1%). CONCLUSIONS: The percentage of WRA cases from exposure to cleaning products from 1998-2012 was unchanged from 1993-1997 indicating that continued and additional prevention efforts are needed to reduce unnecessary use, identify safer products, and implement safer work processes.

Andrew Vernon and co-authors discuss adherence to therapy and its measurement in tuberculosis treatment trials.

Flavorings-related lung disease is a potentially disabling and sometimes fatal lung disease of workers making or using flavorings. First identified almost 20 years ago in microwave popcorn workers exposed to butter-flavoring vapors, flavorings-related lung disease remains a concern today. In some cases, workers develop bronchiolitis obliterans, a severe form of fixed airways disease. Affected workers have been reported in microwave popcorn, flavorings, and coffee production workplaces. Volatile alpha-dicarbonyl compounds, particularly diacetyl (2,3-butanedione) and 2,3-pentanedione, are implicated in the etiology. Published studies on diacetyl and 2,3-pentanedione document their ability to cause airway epithelial necrosis, damage biological molecules, and perturb protein homeostasis. With chronic exposure in rats, they produce airway fibrosis resembling bronchiolitis obliterans. To add to this knowledge, we recently evaluated airway toxicity of the 3-carbon alpha-dicarbonyl compound, methylglyoxal. Methylglyoxal inhalation causes epithelial necrosis at even lower concentrations than diacetyl. In addition, we investigated airway toxicity of mixtures of diacetyl, acetoin, and acetic acid, common volatiles in butter flavoring. At ratios comparable to workplace scenarios, the mixtures or diacetyl alone, but not acetic acid or acetoin, cause airway epithelial necrosis. These new findings add to existing data to implicate alpha-dicarbonyl compounds in airway injury and flavorings-related lung disease.

Objective: Concurrent asthma and chronic obstructive pulmonary disease (COPD) diagnoses occur in 15%-20% of patients, and have been associated with worse health outcomes than asthma or COPD alone. Work-related asthma (WRA), asthma that is caused or made worse by exposures in the workplace, is characterized by poorly controlled asthma. The objective of this study was to assess the proportion of ever-employed adults (>/=18 years) with current asthma who have been diagnosed with COPD, by WRA status. Methods: Data from 23 137 respondents to the 2012-2014 Behavioral Risk Factor Surveillance System Asthma Call-back Survey from 31 states and the District of Columbia were examined. Logistic regression was used to calculate adjusted prevalence ratios (PRs), examining six disjoint categories of WRA-COPD overlap with non-WRA/no COPD as the referent category. Results: An estimated 51.9% of adults with WRA and 25.6% of adults with non-WRA had ever been diagnosed with COPD. Adults with WRA/COPD were more likely than those with non-WRA/no COPD to have an asthma attack (PR = 1.77), urgent treatment for worsening asthma (PR = 2.85), an asthma-related emergency room visit (PR = 4.21), overnight stay in a hospital because of asthma (PR = 6.57), an activity limitation on 1-13 days (PR = 2.01) or >/=14 days (PR = 5.02), and very poorly controlled asthma (PR = 3.22). Conclusions: COPD was more frequently diagnosed among adults with WRA than those with non-WRA, and adults diagnosed with both WRA and COPD appear to have more severe adverse asthma outcomes than those with non-WRA and no COPD.

BACKGROUND: Understanding measurement error in sodium and potassium intake is essential for assessing population intake and studying associations with health outcomes. OBJECTIVE: The aim of this study was to compare sodium and potassium intake derived from 24-h dietary recall (24HDR) with intake derived from 24-h urinary excretion (24HUE). DESIGN: Data were analyzed from 776 nonpregnant, noninstitutionalized US adults aged 20-69 y who completed 1-to-2 24HUE and 24HDR measures in the 2014 NHANES. A total of 1190 urine specimens and 1414 dietary recalls were analyzed. Mean bias was estimated as mean of the differences between individual mean 24HDR and 24HUE measurements. Correlations and attenuation factors were estimated using the Kipnis joint-mixed effects model accounting for within-person day-to-day variability in sodium excretion. The attenuation factor reflects the degree to which true associations between long-term intake (estimated using 24HUEs) and a hypothetical health outcome would be approximated using a single 24HDR: values near 1 indicate close approximation and near 0 indicate bias toward null. Estimates are reported for sodium, potassium, and the sodium: potassium (Na/K) ratio. Model parameters can be used to estimate correlations/attenuation factors when multiple 24HDRs are available. RESULTS: Overall, mean bias for sodium was -452 mg (95% CI: -646, -259), for potassium -315 mg (CI: -450, -179), and for the Na/K ratio -0.04 (CI: -0.15, 0.07, NS). Using 1 24HDR, the attenuation factor for sodium was 0.16 (CI: 0.09, 0.21), for potassium 0.25 (CI:0.16, 0.36), and for the Na/K ratio 0.20 (CI: 0.10, 0.25). The correlation for sodium was 0.27 (CI: 0.16, 0.37), for potassium 0.35 (CI: 0.26, 0.55), and for the Na/K ratio 0.27 (CI: 0.13, 0.32). CONCLUSIONS: Compared with 24HUE, using 24HDR underestimates mean sodium and potassium intake but is unbiased for the Na/K ratio. Additionally, using 24HDR as a measure of exposure in observational studies attenuates the true associations of sodium and potassium intake with health outcomes.