BACKGROUND: During the 2018-20 Ebola virus disease outbreak in the Democratic Republic of the Congo, thousands of patients received unprecedented vaccination, monoclonal antibody (mAb) therapy, or both, leading to a large number of survivors. We aimed to report the clinical, virological, viral genomic, and immunological features of two previously vaccinated and mAb-treated survivors of Ebola virus disease in the Democratic Republic of the Congo who developed second episodes of disease months after initial discharge, ultimately complicated by fatal meningoencephalitis associated with viral persistence. METHODS: In this case report study, we describe the presentation, management, and subsequent investigations of two patients who developed recrudescent Ebola virus disease and subsequent fatal meningoencephalitis. We obtained data from epidemiological databases, Ebola treatment units, survivor programme databases, laboratory datasets, and hospital records. Following national protocols established during the 2018-20 outbreak in the Democratic Republic of the Congo, blood, plasma, and cerebrospinal fluid (CSF) samples were collected during the first and second episodes of Ebola virus disease from both individuals and were analysed by molecular (quantitative RT-PCR and next-generation sequencing) and serological (IgG and IgM ELISA and Luminex assays) techniques. FINDINGS: The total time between the end of the first Ebola virus episode and the onset of the second episode was 342 days for patient 1 and 137 days for patient 2. In both patients, Ebola virus RNA was detected in blood and CSF samples during the second episode of disease. Complete genomes from CSF samples from this relapse episode showed phylogenetic relatedness to the genome sequenced from blood samples collected from the initial infection, confirming in-host persistence of Ebola virus. Serological analysis showed an antigen-specific humoral response with typical IgM and IgG kinetics in patient 1, but an absence of an endogenous adaptive immune response in patient 2. INTERPRETATION: We report the first two cases of fatal meningoencephalitis associated with Ebola virus persistence in two survivors of Ebola virus disease who had received vaccination and mAb-based treatment in the Democratic Republic of the Congo. Our findings highlight the importance of long-term monitoring of survivors, including continued clinical, virological, and immunological profiling, as well as the urgent need for novel therapeutic strategies to prevent and mitigate the individual and public health consequences of Ebola virus persistence. FUNDING: Ministry of Health of the Democratic Republic of the Congo, Institut National de Recherche Biomédicale, Infectious Disease Rapid Response Reserve Fund, US Centers for Disease Control and Prevention, French National Research Institute for Development, and WHO.

The goals of the Association for Molecular Pathology (AMP) Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum set of variant alleles (Tier 1) and an extended list of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The AMP PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx testing across clinical laboratories. This document will focus on clinical DPYD PGx testing that may be applied to all DPD-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.

Given the high and growing prevalence of obesity among adults in the United States, obesity treatment and prevention are important topics in biomedical and public health research. Although researchers recognize the significance of this problem, much remains unknown about safe and effective prevention and treatment of obesity in adults. In response to the worsening obesity epidemic and the many unknowns regarding the disease, a group of key scientific and program staff members of the National Institutes of Health (NIH) and other federal and non-government agencies gathered virtually in September 2021 to discuss the current state of obesity research, research gaps, and opportunities for future research in adult obesity prevention and treatment. The current article synthesizes presentations given by attendees and shares their organizations' current initiatives and identified gaps and opportunities. By integrating the information discussed in the meeting and current initiatives, we identify potential targets and overlapping priorities for future research, including health equity and disparities in obesity, the heterogeneity of obesity, and the use of technological and innovative approaches in interventions.

PROBLEM/CONDITION: Elimination of tuberculosis (TB) is defined as reducing TB disease incidence in the United States to less than 1 case per million persons per year. In 2022, TB incidence in the United States was 2.5 TB cases per 100,000 persons. CDC's TB program developed a set of national TB indicators to evaluate progress toward TB elimination through monitoring performance of state and city TB program activities. Examining TB indicator data enables state- and city-level TB programs to identify areas for program evaluation and improvement activities. These data also help CDC identify states and cities that might benefit from technical assistance. PERIOD COVERED: The 5-year period for which the most recent data were available for each of five indicators: 1) overall TB incidence (2018-2022), 2) TB incidence among non-U.S.-born persons (2018-2022), 3) percentage of persons with drug susceptibility results reported (2018-2022), 4) percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment (2017-2021), and 5) percentage of patients with completion of TB therapy within 12 months (2016-2020). DESCRIPTION OF SYSTEM: The National TB Indicators Project (NTIP) is a web-based performance monitoring tool that uses national TB surveillance data reported through the National TB Surveillance System and the Aggregate Reports for TB Program Evaluation. NTIP was developed to facilitate the use of existing data to help TB program staff members prioritize activities, monitor progress, and focus program improvement efforts. The following five indicators were selected for this report because of their importance in Federal TB funding allocation and in accelerating the decline in TB cases: 1) overall TB incidence in the United States, 2) TB incidence among non-U.S.-born persons, 3) percentage of persons with drug susceptibility results reported, 4) percentage of contacts to sputum AFB smear-positive TB cases who completed treatment for LTBI, and 5) percentage of patients with completion of TB therapy within 12 months. For this report, 52 TB programs (50 states, the District of Columbia, and New York City) were categorized into terciles based on the 5-year average number of TB cases reported to National TB Surveillance System. This grouping allows comparison of TB programs that have similar numbers of TB cases and allocates a similar number of TB programs to each category. The following formula was used to calculate the relative change by TB program for each indicator: [(% from year 5 - % from year 1 ÷ % from year 1) × 100]. RESULTS: During the 5-year period for which the most recent data were available, most TB programs had improvements in reducing overall TB incidence (71.2%) and increasing the percentage of contacts receiving a diagnosis of LTBI who completed LTBI treatment (55.8%); the majority of programs (51.0%) also had improvements in reducing incidence among non-U.S.-born persons. The average percentage of persons with drug susceptibility results reported in most jurisdictions (28 of 52, [53.9%]) met or exceeded the 5-year national average of 97% (2018-2022). The percentage of contacts to sputum acid-fast bacillus (AFB) smear-positive TB patients with newly diagnosed latent TB infection (LTBI) who completed treatment increased in 29 of 52 (55.8%) jurisdictions from 2017 to 2021, signifying that, for most jurisdictions, steps have been taken to enhance performance in this area. The average percentage of patients with completion of TB therapy within 12 months was at or above the national average of 89.7% in approximately two-thirds (32 of 52 [61.5%]) of jurisdictions. INTERPRETATION: This report is the first to describe a 5-year relative change for TB program performance. These results suggest that TB programs are making improvements in activities that help identify persons with TB and LTBI and ensure patients complete treatment in a timely manner. PUBLIC HEALTH ACTION: Use of NTIP data from individual TB programs enables a more detailed examination of trends in program performance and identification of areas for program improvement. Assessing indicator trends by TB program provides an opportunity to gain a better understanding of program performance in comparison to other programs. It can also facilitate communication between programs regarding successes and challenges in program improvement. This information is valuable for TB programs to allocate resources effectively and provide additional context on TB control for public health policymakers.

BACKGROUND: Healthcare-associated infections are prevalent in low- and middle-income countries and may be reduced through proper hand hygiene (HH) adherence during patient care. AIM: We produced and distributed alcohol-based hand rub (ABHR) to 19 public primary and secondary-level public healthcare facilities in Quetzaltenango, Guatemala, and carried out HH observations to assess healthcare workers' (HCWs) HH adherence, and to identify factors associated with this practice. HH adherence was defined as washing hands with soap and water or using ABHR. METHODS: Observations were conducted before (2021, baseline) and after (2022, follow-up) ABHR distribution to evaluate the evolution of HH practices over time. Bivariate comparisons and mixed-effects logistic regression models were used to explore associations between HH adherence and the following independent variables: healthcare facility level, type of contact performed, timing of HH performance, occupational category of HCW and materials present (e.g. water, soap, ABHR) FINDINGS: We observed 243 and 300 patient interactions among 67 and 82 HCWs at each time point respectively. HH adherence was low for both observation periods (40% at baseline and 35% at follow-up). HCWs were more likely to adhere to HH during invasive contacts, after patient contact, and if HCW was a physician. CONCLUSION: HH adherence varied by scenario, which underscores the importance of addressing multiple determinants of behaviour change to improve adherence. This requires interventions implemented with a multimodal approach that includes both increasing access to HH materials and infrastructure, as well as HH education and training, monitoring and feedback, reminders, and promoting a HH safety culture.

INTRODUCTION: Social risk factors such as food insecurity and lack of transportation can negatively affect health outcomes, yet implementation of screening and referral for social risk factors is limited in medical settings, particularly in cancer survivorship. METHODS: We conducted 18 qualitative, semistructured interviews among oncology teams in 3 health systems in Washington, DC, during February and March 2022. We applied the Exploration, Preparation, Implementation, Sustainment Framework to develop a deductive codebook, performed thematic analysis on the interview transcripts, and summarized our results descriptively. RESULTS: Health systems varied in clinical and support staff roles and capacity. None of the participating clinics had an electronic health record (EHR)-based process for identifying patients who completed their cancer treatment ("survivors") or a standardized cancer survivorship program. Their capacities also differed for documenting social risk factors and referrals in the EHR. Interviewees expressed awareness of the prevalence and effect of social risk factors on cancer survivors, but none employed a systematic process for identifying and addressing social risk factors. Recommendations for increasing screening for social risk factors included designating a person to fulfill this role, improving data tracking tools in the EHR, and creating systems to maintain up-to-date information and contacts for community-based organizations. CONCLUSION: The complexity of cancer care workflows and lack of reimbursement results in a limited ability for clinic staff members to screen and make referrals for social risk factors. Creating clinical workflows that are flexible and tailored to staffing realities may contribute to successful implementation of a screening and referral program. Improving ongoing communication with community-based organizations to address needs was deemed important by interviewees.

After 27 years of declining U.S. tuberculosis (TB) case counts, the number of TB cases declined considerably in 2020, coinciding with the COVID-19 pandemic. For this analysis, TB case counts were obtained from the National TB Surveillance System. U.S. Census Bureau population estimates were used to calculate rates overall, by jurisdiction, birth origin, race and ethnicity, and age group. Since 2020, TB case counts and rates have increased each year. During 2023, a total of 9,615 TB cases were provisionally reported by the 50 U.S. states and the District of Columbia (DC), representing an increase of 1,295 cases (16%) as compared with 2022. The rate in 2023 (2.9 per 100,000 persons) also increased compared with that in 2022 (2.5). Forty states and DC reported increases in 2023 in both case counts and rates. National case counts increased among all age groups and among both U.S.-born and non-U.S.-born persons. Although TB incidence in the United States is among the lowest in the world and most U.S. residents are at minimal risk, TB continues to cause substantial global morbidity and mortality. This postpandemic increase in U.S. cases highlights the importance of continuing to engage communities with higher TB rates and their medical providers in TB elimination efforts and strengthening the capacity in public health programs to carry out critical disease control and prevention strategies.

BACKGROUND: The Democratic Republic of the Congo has had 15 Ebola virus disease (EVD) outbreaks, from 1976 to 2023. On June 1, 2020, the Democratic Republic of the Congo declared an outbreak of EVD in the western Équateur Province (11th outbreak), proximal to the 2018 Tumba and Bikoro outbreak and concurrent with an outbreak in the eastern Nord Kivu Province. In this Article, we assessed whether the 11th outbreak was genetically related to previous or concurrent EVD outbreaks and connected available epidemiological and genetic data to identify sources of possible zoonotic spillover, uncover additional unreported cases of nosocomial transmission, and provide a deeper investigation into the 11th outbreak. METHODS: We analysed epidemiological factors from the 11th EVD outbreak to identify patient characteristics, epidemiological links, and transmission modes to explore virus spread through space, time, and age groups in the Équateur Province, Democratic Republic of the Congo. Trained field investigators and health professionals recorded data on suspected, probable, and confirmed cases, including demographic characteristics, possible exposures, symptom onset and signs and symptoms, and potentially exposed contacts. We used blood samples from individuals who were live suspected cases and oral swabs from individuals who were deceased to diagnose EVD. We applied whole-genome sequencing of 87 available Ebola virus genomes (from 130 individuals with EVD between May 19 and Sept 16, 2020), phylogenetic divergence versus time, and Bayesian reconstruction of phylogenetic trees to calculate viral substitution rates and study viral evolution. We linked the available epidemiological and genetic datasets to conduct a genomic and epidemiological study of the 11th EVD outbreak. FINDINGS: Between May 19 and Sept 16, 2020, 130 EVD (119 confirmed and 11 probable) cases were reported across 13 Équateur Province health zones. The individual identified as the index case reported frequent consumption of bat meat, suggesting the outbreak started due to zoonotic spillover. Sequencing revealed two circulating Ebola virus variants associated with this outbreak-a Mbandaka variant associated with the majority (97%) of cases and a Tumba-like variant with similarity to the ninth EVD outbreak in 2018. The Tumba-like variant exhibited a reduced substitution rate, suggesting transmission from a previous survivor of EVD. INTERPRETATION: Integrating genetic and epidemiological data allowed for investigative fact-checking and verified patient-reported sources of possible zoonotic spillover. These results demonstrate that rapid genetic sequencing combined with epidemiological data can inform responders of the mechanisms of viral spread, uncover novel transmission modes, and provide a deeper understanding of the outbreak, which is ultimately needed for infection prevention and control during outbreaks. FUNDING: WHO and US Centers for Disease Control and Prevention.

BACKGROUND: Hand hygiene (HH) is an important practice that prevents transmission of infectious diseases, such as COVID-19. However, in resource-limited areas, where water and soap are not always available, it can be difficult to practice HH correctly and at appropriate moments. The purpose of this study was to assess HH knowledge and behaviors among students from six elementary schools in Quetzaltenango, Guatemala to identify gaps that could later inform interventions to improve HH. METHODS: We conducted knowledge, attitude, and practices (KAP) surveys among primary school students during the COVID-19 pandemic in July 2022. We also observed students' HH practices at three different moments during the day, making note of the use of the HH station and materials, duration of handwashing, presence of a HH assistant, and the students' sex. We also used the Quantitative Personal Hygiene Assessment Tool (qPHAT), to measure hand dirtiness before eating, after restroom use, and upon arriving to school. RESULTS: We surveyed 109 students across six schools. Mean scores were 4 out of 5 for knowledge, 8 out of 8 for attitudes, and 6 out of 7 for HH practices. Most students identified "before eating" as a critical moment for HH (68.8%), fewer identified "after restroom use" (31.2%), and no students mentioned HH being necessary "after coughing or sneezing". We observed 326 HH opportunities of which 51.2% performed correct HH (used water and soap for at least 20 s or used alcohol-based hand rub, where materials were available). We collected 82 qPHAT hand swabs. A Kruskal Wallis test revealed a significant difference in hand dirtiness between entering the school and after restroom use (p = 0.017), but no significant difference before eating and after entering the school (p = 0.6988). CONCLUSIONS: The results from the KAP survey show high scores, however correct identification of key moments for HH was relatively uncommon, especially after restroom use and after coughing or sneezing. Additionally, half of HH opportunities observed had correct HH practices and on average, hands were dirtiest when arriving at school. These findings will inform interventions to improve HH practices and behaviors, which will be evaluated with follow-up data collection.

In response to the COVID-19 pandemic, we established and sustained local production of Alcohol-Based Hand Rub (ABHR) at a district scale for healthcare facilities and community, public locations in four districts in Uganda. District officials provided space and staff for production units. The project renovated space for production, trained staff on ABHR production, and transported ABHR to key locations. The production officer conducted internal ABHR quality assessments while trained district health inspectors conducted external quality assessments prior to distribution. Information, education, and communication materials accompanied ABHR distribution. Onsite ABHR consumption was moni-tored by site staff using stock cards. On average, it took 11 days (range: 8–14) and 5,760 USD (range: 4,400–7,710) to setup a production unit. From March to December 2021, 21,600 L of quality-controlled ABHR were produced for 111 healthcare facilities and community locations at an average cost of 4.30 USD/L (range: 3.50–5.76). All ABHR passed both internal and external quality control (average ethanol concentration of 80%, range: 78–81%). This case study demonstrated that establishing centralized, local production of quality-controlled, affordable ABHR at a district-wide scale is feasible and strengthens the ability of healthcare workers and community locations to access and use ABHR during infectious disease outbreaks in low-resource countries. © 2023 The Authors.

Water, sanitation, and hygiene (WASH) services in schools are essential to reduce infectious disease transmission, including that of COVID-19. This study aimed to establish a baseline of WASH services in six public elementary schools in Guatemala, with a focus on hand hygiene. We used the WHO/UNICEF Joint Monitoring Programme (JMP) report indicators to assess the WASH infrastructure at each school. We collected water samples from easily accessible water points (pilas, or bathroom sinks) at each school to test for the presence of total coliforms and E. coli. In-depth interviews were carried out with teachers to understand hand hygiene practices and systems at school. Results indicate that all schools had water available at the time of the survey. All water samples at four schools tested positive for total coliforms and at one school, positive for E. coli. All schools had sanitation facilities, but services were limited. Only 43% of handwashing stations at schools had soap available. No school had disability-inclusive WASH services. Financial constraints and a lack of appropriate WASH infrastructure were the main barriers reported by teachers to meet hand hygiene needs at school. Appropriate access to WASH infrastructure and supplies could increase hand hygiene practices and improve learning conditions for students.

Motor vehicle crashes (MVCs) are the leading cause of fatal work-related injuries in the United States. Research assessing sociodemographic risk disparities for work-related MVCs is limited, yet structural and systemic inequities at work and during commutes likely contribute to disproportionate MVC risk. This paper summarizes the literature on risk disparities for work-related MVCs by sociodemographic and employment characteristics and identifies worker populations that have been largely excluded from previous research. The social-ecological model is used as a framework to identify potential causes of disparities at five levels-individual, interpersonal, organizational, community, and public policy. Expanded data collection and analyses of work-related MVCs are needed to understand and reduce disparities for pedestrian workers, workers from historically marginalized communities, workers with overlapping vulnerabilities, and workers not adequately covered by employer policies and safety regulations. In addition, there is a need for more data on commuting-related MVCs in the United States. Inadequate access to transportation, which disproportionately affects marginalized populations, may make travel to and from work less safe and limit individuals' access to employment. Identifying and remedying inequities in work-related MVCs, whether during the day or while commuting, will require the efforts of industry and multiple public sectors, including public health, transportation, and labor.

To understand access to and use of hand hygiene in healthcare facilities (HCFs) and community locations during the COVID-19 pandemic, we evaluated factors associated with hand hygiene in 60 priority HCFs and community locations in two border districts in Uganda. We assessed water and hand hygiene resource availability and observed hand hygiene practice by staff or patrons. Regression modeling estimated factors associated with the availability or use of hand hygiene. In HCFs, most inpatient (61%), outpatient (71%), and laboratory or staff (90%) rooms contained hand hygiene materials. Only 38% of community locations had hand hygiene materials at all entrances and exits, 35% of congregation areas had hand hygiene materials. Overall, 38% of healthcare staff, 48% of patrons post-latrine use, and 21% of patrons entering or exiting community locations practiced hand hygiene. HCF hand hygiene access was lower in inpatient rooms (odds ratio [OR] = 0.17, 95% CI: 0.06-0.45) and outpatient rooms (OR = 0.23, 95% CI: 0.07-0.70) compared with laboratory/staff rooms. HCF hand hygiene practice was higher for doctors than nurses (OR = 3.58, 95% CI: 1.15-11.14) and with new versus existing patient encounters (OR = 2.27, 95% CI: 1.20-4.27); it was lower before versus after patient contact for both invasive (OR = 0.03, 95% CI: 0.00-0.20) and noninvasive (OR = 0.66, 95% CI: 0.45-0.95) procedures. In community settings, hand hygiene practice after using the latrine was higher than at an entrances/exits (OR = 3.39, 95% CI: 2.08-5.52). Hand hygiene rates were relatively low in healthcare and community settings. Greater emphasis on hand hygiene before patient interactions (at HCFs) and at community entrances/exits for patrons is also needed.

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This document series provides recommendations for a minimum panel of variant alleles (tier 1) and an extended panel of variant alleles (tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, and other technical considerations for PGx testing when developing these recommendations. The goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This document will focus on clinical CYP3A4 and CYP3A5 PGx testing that may be applied to all CYP3A4- and CYP3A5-related medications. These recommendations are not to be interpreted as prescriptive but to provide a reference guide.

Introduction: Over half of fatal occupational injuries in the oil and gas extraction (OGE) industry are due to transportation incidents. While driving for work is common in this industry and risky driving behaviors have been identified as contributing factors to fatal crashes among OGE workers, limited information is available on the frequency of risky driving behaviors and employer policies to reduce these behaviors. Methods: Researchers conducted a cross-sectional survey of OGE workers in three states. Responses from 363 OGE workers who drive as a part of their work duties were analyzed to evaluate relationships between self-reported risky driving behaviors (i.e., speeding, cell phone use, and driving unbelted) and awareness of motor-vehicle safety policies by their employers. Results: Hands-free cell phone use was the most common risky driving behavior among participants (59.8%), while a hands-free cell phone ban was the least commonly reported employer motor-vehicle safety policy (34.7%). Multiple logistic regression results identified longer work and commuting hours, lack of employer motor-vehicle safety policies, having ever been in a work crash, and being employed by an operator to be significantly associated with risky driving behaviors. Conclusions: Workers whose employers lacked motor-vehicle safety policies were more likely to engage in risky driving behaviors. Practical applications: Results of this survey support the implementation of motor-vehicle safety interventions such as bans on texting and handheld and hands-free cell phone use, speed management, and in-vehicle monitoring systems by OGE employers as well as research focusing on the effectiveness of these interventions in OGE. Additional research could examine worker driving behaviors through self-reported data in combination with objective measures.

Incidence of reported tuberculosis (TB) decreased gradually in the United States during 1993-2019, reaching 2.7 cases per 100,000 persons in 2019. Incidence substantially declined in 2020 to 2.2, coinciding with the COVID-19 pandemic (1). Proposed explanations for the decline include delayed or missed TB diagnoses, changes in migration and travel, and mortality among persons susceptible to TB reactivation (1). Disparities (e.g., by race and ethnicity) in TB incidence have been described (2). During 2021, TB incidence partially rebounded (to 2.4) but remained substantially below that during prepandemic years, raising concerns about ongoing delayed diagnoses (1). During 2022, the 50 U.S. states and the District of Columbia (DC) provisionally reported 8,300 TB cases to the National Tuberculosis Surveillance System. TB incidence was calculated using midyear population estimates and stratified by birth origin and by race and ethnicity. During 2022, TB incidence increased slightly to 2.5 although it remained lower than during prepandemic years.* Compared with that in 2021, TB epidemiology in 2022 was characterized by more cases among non-U.S.-born persons newly arrived in the United States; higher TB incidence among non-Hispanic American Indian or Alaska Native (AI/AN) and non-Hispanic Native Hawaiian or other Pacific Islander (NH/OPI) persons and persons aged ≤4 and 15-24 years; and slightly lower incidence among persons aged ≥65 years. TB incidence appears to be returning to prepandemic levels. TB disparities persist; addressing these disparities requires timely TB diagnosis and treatment to interrupt transmission and prevention of TB through treatment of latent TB infection (LTBI).

The occurrence and antimicrobial resistance (AMR) of typhoid fever in the WHO Eastern Mediterranean Region (EMR) are poorly characterized. Robust surveillance data are needed to inform strategies for typhoid control and prevention in the region. We conducted a systematic review of typhoid fever occurrence, complications, and AMR patterns in EMR countries. We identified 70 studies published from 1990 to 2021, including a total of 44,541 cases with blood culture confirmed typhoid fever in 12 EMR countries, with 48 (69%) studies and 42,008 cases from Pakistan. Among 56 studies with AMR data, fluroquinolone (68% of 13,013 tested isolates), and multidrug resistance (40% of 15,765 tested isolates) were common. Forty (57%) of the 56 studies were from Pakistan, and all reports of extensively drug resistant Salmonella Typhi (48% of 9,578 tested isolates) were from studies in Pakistan. Our findings support the need for continued efforts to strengthen surveillance and laboratory capacity for blood-culture detection of typhoid fever in the region, including data from an ongoing collaboration among CDC, the American University of Beirut, and the WHO EMR office.

BACKGROUND: US tuberculosis (TB) guidelines recommend treatment ≥6 months with a regimen composed of multiple effective anti-TB drugs. Since 2003, a 4-month regimen for a specific subset of TB patients has also been recommended. METHODS: We used 2011-2018 US National Tuberculosis Surveillance System data to characterize factors associated with 4-month (111-140 days) therapy among adult patients who had completed treatment and were potentially eligible at that time for 4-month therapy (culture-negative pulmonary-only TB, absence of certain risk factors, and initial treatment that included pyrazinamide). We used modified Poisson regression with backward elimination of main effect variables to calculate adjusted relative risks (aRRs). RESULTS: During 2011-2018, 63 393 adults completed TB treatment: 5560 (8.8%) were potentially eligible for 4-month therapy; of these, 5560 patients (79%) received >4-month therapy (median, 193 days or ∼6 months). Patients with cavitary disease were more likely to receive >4-month therapy (aRR, 1.10; 95% CI, 1.07-1.14) vs patients without cavitary disease. Patients more likely to receive 4-month therapy included patients treated by health departments vs private providers only (aRR, 0.94; 95% CI, 0.91-0.98), those in the South and West vs the Midwest, non-US-born persons (aRR, 0.95; 95% CI, 0.91-0.99) vs US-born persons, and aged 25-64 years vs 15-24 years. CONCLUSIONS: Most patients potentially eligible for 4-month therapy were treated with standard 6-month courses. Beyond clinical eligibility criteria, other patient- and program-related factors might be more critical determinants of treatment duration.

CONTEXT: Schools can play an important role in supporting a healthy lifestyle by offering nutritious foods and beverages and providing opportunities for physical activity. A healthy diet and regular physical activity may reduce the risk of obesity. This manuscript reports on a Community Guide systematic review examining the effectiveness of interventions in schools combining school meal or fruit and vegetable snack programs and physical activity. EVIDENCE ACQUISITION: Studies meeting the intervention definition were identified from a literature search (search period: January 1990-November 2019). Community Guide systematic review methods were used to assess effectiveness as measured by dietary behavior, physical activity, and weight changes; analyses were conducted in 2020. EVIDENCE SYNTHESIS: Interventions (n=24 studies) were considered effective for increasing physical activity (median increase=21.8 minutes/day; interquartile interval= -0.8 to 27.4 minutes/day), modestly increasing fruit and vegetable intake (median relative increase=12.1%; interquartile interval= -4.6%, 73.4%), and decreasing the prevalence of overweight and obesity (median decrease=2.5 percentage points; interquartile interval= -8.1, -1.6 percentage points) among elementary school students through sixth grade. There were not enough studies to determine the effectiveness of interventions for middle- and high-school students. CONCLUSIONS: School meal or fruit and vegetable snack interventions combined with physical activity were effective in increasing physical activity, with modest effects for improving fruit and vegetable consumption and reducing the prevalence of overweight and obesity among elementary students. These results may inform researchers and school administrators about healthy eating and physical activity interventions.

Continuity of key water, sanitation, and hygiene (WASH) infrastructure and WASH practices-for example, hand hygiene-are among several critical community preventive and mitigation measures to reduce transmission of infectious diseases, including COVID-19 and other respiratory diseases. WASH guidance for COVID-19 prevention may combine existing WASH standards and new COVID-19 guidance. Many existing WASH tools can also be modified for targeted WASH assessments during the COVID-19 pandemic. We partnered with local organizations to develop and deploy tools to assess WASH conditions and practices and subsequently implement, monitor, and evaluate WASH interventions to mitigate COVID-19 in low- and middle-income countries in Latin America and the Caribbean and Africa, focusing on healthcare, community institution, and household settings and hand hygiene specifically. Employing mixed-methods assessments, we observed gaps in access to hand hygiene materials specifically despite most of those settings having access to improved, often onsite, water supplies. Across countries, adherence to hand hygiene among healthcare providers was about twice as high after patient contact compared to before patient contact. Poor or non-existent management of handwashing stations and alcohol-based hand rub (ABHR) was common, especially in community institutions. Markets and points of entry (internal or external border crossings) represent congregation spaces, critical for COVID-19 mitigation, where globally-recognized WASH standards are needed. Development, evaluation, deployment, and refinement of new and existing standards can help ensure WASH aspects of community mitigation efforts that remain accessible and functional to enable inclusive preventive behaviors.

While risk of fomite transmission of SARS-CoV-2 is considered low, there is limited environmental data within households. This January-April 2021 investigation describes frequency and types of surfaces positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) among residences with ≥1 SARS-CoV-2 infection, and associations of household characteristics with surface RT-PCR and viable virus positivity. Of 1232 samples from 124 households, 27.8% (n = 342) were RT-PCR positive with nightstands (44.1%) and pillows (40.9%) most frequently positive. SARS-CoV-2 lineage, documented household transmission, greater number of infected persons, shorter interval between illness onset and sampling, total household symptoms, proportion of infected persons ≤12 years old, and persons exhibiting upper respiratory symptoms or diarrhea were associated with more positive surfaces. Viable virus was isolated from 0.2% (n = 3 samples from one household) of all samples. This investigation suggests that while SARS-CoV-2 on surfaces is common, fomite transmission risk in households is low.

The goals of the Association for Molecular Pathology Clinical Practice Committee's Pharmacogenomics (PGx) Working Group are to define the key attributes of pharmacogenetic alleles recommended for clinical testing and a minimum set of variants that should be included in clinical PGx genotyping assays. This article provides recommendations for a minimum panel of variant alleles (Tier 1) and an extended panel of variant alleles (Tier 2) that will aid clinical laboratories when designing assays for PGx testing. The Association for Molecular Pathology PGx Working Group considered the functional impact of the variant alleles, allele frequencies in multiethnic populations, the availability of reference materials, as well as other technical considerations for PGx testing when developing these recommendations. The ultimate goal of this Working Group is to promote standardization of PGx gene/allele testing across clinical laboratories. This article focuses on clinical TPMT and NUDT15 PGx testing, which may be applied to all thiopurine S-methyltransferase (TPMT) and nudix hydrolase 15 (NUDT15)-related medications. These recommendations are not to be interpreted as prescriptive, but to provide a reference guide.

Numerous health and safety hazards exist at U.S. onshore oil and gas extraction worksites. Higher fatal injury rates have been reported among drilling and servicing companies, which are more likely to employ workers in construction and extraction occupations, compared to operators that employ more workers in management and office and administrative support roles. However, there is little information describing the extent to which workers encounter these hazards, are provided hazard mitigation strategies by their employers, or use personal protective equipment (PPE). A cross-sectional survey of 472 U.S. oil and gas extraction workers was conducted to identify and characterize factors related to on-the-job fatalities, injuries, and illnesses and determine the health and safety concerns of workers. Workers were employed by servicing companies (271/472, 57.4%), drilling contractors (106/472, 22.5%), and operators (95/472, 20.1%). The likelihood of contact with hazardous substances varied by substance and company type. Drilling and servicing employees had significantly higher odds of self-reported contact with pipe dope (OR(drilling)=10.07, 95% CI: 1.74-63.64; OR(servicing)=5.95, 95% CI: 2.18-18.34), diesel exhaust (OR(drilling)=2.28, 95% CI: 1.15-5.05; OR(servicing)=4.93, 95% CI: 2.73-10.32), and drilling mud (OR(drilling)=24.36, 95% CI: 4.45-144.69; OR(servicing)=3.48, 95% CI: 1.24-12.20), compared to operators. Safety policies, programs, and trainings were commonly reported by workers, although substance-specific training (e.g., respirable crystalline silica hazards) was less common. Differences in self-reported employer PPE requirements and worker use of PPE when needed or required for safety highlight a need for novel strategies to improve use of PPE. Overall, this study highlights differences in work conditions by company type and uncovers gaps in employer administrative controls and PPE use.

Pharmacogenetic testing is increasingly provided by clinical and research laboratories; however, only a limited number of quality control and reference materials (RMs) are currently available for many of the TPMT and NUDT15 variants included in clinical tests. To address this need, the Division of Laboratory Systems, Centers for Disease Control and Prevention (CDC) based Genetic Testing Reference Material Coordination Program (GeT-RM), in collaboration with members of the pharmacogenetic testing and research communities and the Coriell Institute for Medical Research, has characterized 19 DNA samples derived from Coriell cell lines. DNA samples were distributed to four volunteer testing laboratories for genotyping using a variety of commercially available and laboratory developed tests and/or Sanger sequencing. Of the 12 samples characterized for TPMT, newly identified variants include TPMT*2, *6, *12, *16, *21, *24, *32, *33, *40; for the 7 NUDT15 reference material samples, newly identified variants are NUDT15*2, *3, *4, *5, *6, and *9. In addition, a novel haplotype, TPMT*46, was identified in this study. Pre-existing data on an additional 11 Coriell samples, as well as some supplemental testing, was utilized to create comprehensive reference material panels for TPMT and NUDT15. These publicly available and well characterized materials can be used to support the quality assurance and quality control programs of clinical laboratories performing clinical pharmacogenetic testing.

BACKGROUND: Oil and gas extraction (OGE) workers in the United States experience high fatality rates, with motor vehicle crashes the leading cause of death. Land-based OGE workers drive frequently to remote and temporary worksites. Limited information is available on factors that may influence crash risk for this workforce. METHODS: A cross-sectional survey of 500 land-based OGE workers examined work schedules and hours, commuting, sleep, employer policies, and their relationship to potentially harmful events while driving. RESULTS: Over 60% of participants worked 12 or more hours per day. The mean daily roundtrip commuting time was 1.82 h. Longer daily commutes, nonstandard work schedules, less sleep on workdays, and lack of employer policies were associated with one or more risky driving-related outcomes. CONCLUSIONS: Implementation and evaluation of OGE employer policies and programs to limit long work hours, reduce long daily commutes, promote sufficient sleep, and reduce drowsy driving among U.S. OGE workers are needed.

During 1993-2019, the incidence of tuberculosis (TB) in the United States decreased steadily; however, during the later years of that period the annual rate of decline slowed (1) until 2020 when a substantial decline (19.9%) was observed. This sharp decrease in TB incidence might have been related to multiple factors coinciding with the COVID-19 pandemic, including delayed or missed TB diagnoses or a true reduction in TB incidence related to pandemic mitigation efforts and changes in immigration and travel (2). During 2021, a total of 7,860 TB cases were provisionally reported to CDC's National Tuberculosis Surveillance System (NTSS) by the 50 U.S. states and the District of Columbia (DC). National incidence of reported TB (cases per 100,000 persons) rose 9.4% during 2021 (2.37) compared with that in 2020 (2.16) but remained 12.6% lower than the rate during 2019 (2.71).* During 2021, TB incidence increased among both U.S.-born and non-U.S.-born persons. The increased TB incidence observed during 2021 compared with 2020 might be partially explained by delayed diagnosis of cases in persons with symptom onset during 2020; however, the continued, substantial reduction from prepandemic levels raises concern for ongoing underdiagnosis. TB control and prevention services, including early diagnosis and complete treatment of TB and latent TB infection, should be maintained and TB awareness promoted to achieve elimination in the United States.

Pharmacogenetic tests typically target selected sequence variants to identify haplotypes that are often defined by star (*) allele nomenclature. Due to their design, these targeted genotyping assays are unable to detect novel variants that may change the function of the gene product and thereby affect phenotype prediction and patient care. In the current study, 137 DNA samples that were previously characterized by the Genetic Testing Reference Material (GeT-RM) Program using a variety of targeted genotyping methods were recharacterized using targeted and whole genome sequencing analysis. Sequence data were analyzed using three genotype calling tools to identify star allele diplotypes for CYP2C8, CYP2C9 and CYP2C19. The genotype calls from next-generation sequencing (NGS) correlated well to those previously reported, except when novel alleles were present in a sample. Six novel alleles and 38 novel suballeles were identified in the three genes due to identification of variants not covered by targeted genotyping assays. In addition, several ambiguous genotype calls from a previous study were resolved using the NGS and/or long read NGS data. Diplotype calls were mostly consistent between the calling algorithms, although several discrepancies were noted. This study highlights the utility of NGS for pharmacogenetic testing and demonstrates that there are many novel alleles that are yet to be discovered, even in highly characterized genes such as CYP2C9 and CYP2C19.

The National Aeronautics and Space Administration-European Space Agency (NASA-ESA) Mars Sample Return (MSR) campaign involves the collection of samples on Mars by the Perseverance (Mars 2020) rover and their return to Earth. To accomplish this, the Orbiting Sample container (OS) will be sent to Mars to accommodate the collected samples then launched from Mars and returned to Earth, where the samples will be removed for examination in the Sample Return Facility (SRF). Crucial to this entire sequence will be establishment of the required level of cleanliness inside the OS. In February 2021, the NASA Headquarters' Mars Sample Return Program and Office of Planetary Protection assembled an MSR OS Tiger Team (OSTT) to discuss the appropriate cleanliness level options of the interior of the OS. The team's remit was primarily focused on evaluating the trade-offs between Planetary Protection cleanliness levels 4a and 4b. These cleanliness levels are determined by the Committee on Space Research (COSPAR) planetary protection regulations, where 4a requires < 300 bacterial spores/m2 and < 3 x 105 bacterial spores on the spacecraft (in this case, the interior of the OS) and 4b mandates the more stringent requirement of < 30 bacterial spores on the spacecraft. This report documents the consensus opinion submitted by the OSTT that recommended the interior of the OS be cleaned to a 4a requirement with any feasible added effort toward 4b. This report provides, as well, the rationale for that decision.

BACKGROUND: During 2003-2013, 1189 US oil and gas extraction (OGE) workers died while working, resulting in an average annual workplace fatality rate seven times that for all US workers. OGE work commonly involves long hours, shiftwork, irregular schedules, and long commutes, but effects of these factors on fatigue, occupational injury, and illness in OGE are largely unknown. METHODS: A scoping review of relevant OGE research during 2000-2019 was completed and supplemented by input from a NIOSH-sponsored Forum. RESULTS: Seventy-eight papers were identified; 76% reported only offshore research. Five themes for research needs emerged: build knowledge about the impacts of fatigue; explore interactions between on- and off-the-job risk factors; identify and evaluate interventions; assess effectiveness of technology; and increase the diffusion of fatigue risk management information. CONCLUSIONS: Further collaboration between researchers and OGE operators and contractors can lead to action-oriented recommendations to mitigate the effects of fatigue, inadequate sleep, and shiftwork.

Heart disease and stroke are the first and fifth leading causes of death in the United States, respectively. Employers have a unique opportunity to promote cardiovascular health, because >60% of US adults are employed, and most spend half of their waking hours at work. Despite the scope of the opportunity, <1 in 5 businesses implement evidence-based, comprehensive workplace health programs, policies, and practices. Integrated, systems-based workplace health approaches that harness data science and technology may have the potential to reach more employees and be cost-effective for employers. To evaluate the role of the workplace in promoting cardiovascular health across the lifespan, the National Heart, Lung, and Blood Institute, the National Institute for Occupational Safety and Health, and the American Heart Association convened a workshop on March 7, 2019, to share best practices, and to discuss current evidence and knowledge gaps, practical application, and dissemination of the evidence, and the need for innovation in workplace health research and practice. This report presents the broad themes discussed at the workshop and considerations for promoting worker cardiovascular health, including opportunities for future research.