Blastomycosis is a fungal disease caused by inhalation of Blastomyces spores from the environment that can result in severe pulmonary illness and high hospitalization rates. In early March 2023, Public Health Delta and Menominee Counties (Michigan) reported a cluster of blastomycosis cases among paper mill workers to the Michigan Department of Health and Human Services (MDHHS). MDHHS subsequently notified CDC. On March 17, paper mill management requested a health hazard evaluation (HHE) from CDC’s National Institute for Occupational Safety and Health (NIOSH) to investigate potential workplace exposures to Blastomyces and recommend prevention and control measures at the mill. The workplace epidemiologic investigation combined a NIOSH HHE medical survey consisting of a questionnaire on work and health with Blastomyces urine antigen testing of specimens obtained from workers to assist in case finding, with additional case information from MDHHS blastomycosis surveillance data. Assessment of 645 mill workers identified 162 cases of blastomycosis with illness onset during November 1, 2022-May 15, 2023, with the weekly case count peaking at 21 cases in early March 2023. HHE environmental sampling in and around the mill did not identify the source of workers' Blastomyces exposure in the mill. This outbreak was the largest documented blastomycosis outbreak in the United States, and the first associated with a paper mill or an industrial setting. A coordinated public health response facilitated swift prevention measures with recommendations focused on reducing workers' exposure to Blastomyces, including hazard communication, respiratory protection, mill cleaning, and ventilation system improvements.

BACKGROUND: Carbapenemase-producing, carbapenem-resistant Pseudomonas aeruginosa (CP-CRPA) are extensively drug resistant bacteria. We investigated the source of a multistate CP-CRPA outbreak. METHODS: Cases were defined as a U.S. patient's first isolation of P. aeruginosa sequence type 1203 with the carbapenemase gene blaVIM-80 and cephalosporinase gene blaGES-9 from any specimen source collected and reported to CDC between January 1, 2022-May 15, 2023. We conducted a 1:1 matched case-control study at the post-acute care facility with the most cases, assessed exposures associated with case status for all case-patients, and tested products for bacterial contamination. RESULTS: We identified 81 case-patients from 18 states, 27 of whom were identified through surveillance cultures. Four (7%) of 54 case-patients with clinical cultures died within 30 days of culture collection, and four (22%) of 18 with eye infections underwent enucleation. In the case-control study, case-patients had increased odds of receiving artificial tears compared to controls (crude matched OR: 5.0, 95% CI: 1.1, 22.8). Overall, artificial tears use was reported by 61 (87%) of 70 case-patients with information; 43 (77%) of 56 case-patients with brand information reported use of Brand A, an imported, preservative-free, over-the-counter (OTC) product. Bacteria isolated from opened and unopened bottles of Brand A were genetically related to patient isolates. FDA inspection of the manufacturing plant identified likely sources of contamination. CONCLUSIONS: A manufactured medical product serving as the vehicle for carbapenemase-producing organisms is unprecedented in the U.S. The clinical impacts from this outbreak underscore the need for improved requirements for U.S. OTC product importers.

We report 2 cases of pharyngeal monkeypox virus and group A Streptococcus co-infection in the United States. No rash was observed when pharyngitis symptoms began. One patient required intubation before mpox was diagnosed. Healthcare providers should be aware of oropharyngeal mpox manifestations and possible co-infections; early treatment might prevent serious complications.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic.

BACKGROUND: Entomological surveillance is traditionally conducted by supervised teams of trained technicians. However, it is expensive and limiting in the number of sites visited. Surveillance through community-based collectors (CBC) may be more cost-effective and sustainable for longitudinal entomological monitoring. This study evaluated the efficiency of CBCs in monitoring mosquito densities compared to quality-assured sampling conducted by experienced entomology technicians. METHODS: Entomological surveillance employing CBCs was conducted in eighteen clusters of villages in western Kenya using indoor and outdoor CDC light traps and indoor Prokopack aspiration. Sixty houses in each cluster were enrolled and sampled once every month. Collected mosquitoes were initially identified to the genus level by CBCs, preserved in 70% ethanol and transferred to the laboratory every 2 weeks. Parallel, collections by experienced entomology field technicians were conducted monthly by indoor and outdoor CDC light traps and indoor Prokopack aspiration and served as a quality assurance of the CBCs. RESULTS: Per collection, the CBCs collected 80% fewer Anopheles gambiae sensu lato (s.l.) [RR = 0.2; (95% CI 0.14-0.27)] and Anopheles coustani [RR = 0.2; (95% CI 0.06-0.53)] and 90% fewer Anopheles funestus [RR = 0.1; (95% CI 0.08-0.19)] by CDC light traps compared to the quality assured (QA) entomology teams. Significant positive correlations were however observed between the monthly collections by CBCs and QA teams for both An. gambiae and An. funestus. In paired identifications of pooled mosquitoes, the CBCs identified 4.3 times more Anopheles compared to experienced technicians. The cost per person-night was lower in the community-based sampling at $9.1 compared to $89.3 by QA per collection effort. CONCLUSION: Unsupervised community-based mosquito surveillance collected substantially fewer mosquitoes per trap-night compared to quality-assured collection by experienced field teams, while consistently overestimating the number of Anopheles mosquitoes during identification. However, the numbers collected were significantly correlated between the CBCs and the QA teams suggesting that trends observed by CBCs and QA teams were similar. Further studies are needed to evaluate whether adopting low-cost, devolved supervision with spot checks, coupled with remedial training of the CBCs, can improve community-based collections to be considered a cost-effective alternative to surveillance conducted by experienced entomological technicians.

BACKGROUND: Sex and racial/ethnic identity specific cut-points for validating tobacco use using Wave 1 (W1) of the PATH Study were published in 2020. The current study establishes predictive validity of the W1 (2014) urinary cotinine and Total Nicotine Equivalents-2 (TNE-2) cut-points on estimating Wave 4 (W4; 2017) tobacco use. METHODS: For exclusive and polytobacco cigarette use, weighted prevalence estimates based on W4 self-report alone and with exceeding the W1 cut-point were calculated to identify the percentage missed without biochemical verification. Sensitivity and specificity of W1 cut-points on W4 self-reported tobacco use status were examined. Receiver Operating Characteristic curves were used to determine the optimal W4 cut-points to distinguish P30D users from non-users, and evaluate if the cut-points significantly differed from W1. RESULTS: Agreement between W4 self-reported use and exceeding the W1 cut-points was high overall and when stratified by demographic subgroups (0.7- 4.4% of use was missed if relying on self-report alone). The predictive validity of using the W1 cut-points to classify exclusive cigarette and polytobacco cigarette use at W4 was high (>90% sensitivity and specificity, except among polytobacco Hispanic smokers). Cut-points derived using W4 data did not significantly differ from the W1 derived cut-points (e.g., W1 exclusive= 40.5 ng/mL cotinine [95% CI: 26.1-62.8], W4 exclusive = 29.9 ng/ml cotinine [95% CI: 13.5-66.4]), among most demographic subgroups. CONCLUSION: The W1 cut-points remain valid for biochemical verification of self-reported tobacco use in W4. IMPACT: Findings from can be used in clinical and epidemiological studies to reduce misclassification of cigarette smoking status.

The report “Genomic Surveillance for SARS-CoV-2 Variants: Predominance of the Delta (B.1.617.2) and Omicron (B.1.1.529) Variants — United States, June 2021–January 2022” contained several errors.

During June 2017-November 2019, a total 36 patients with carbapenem-resistant Pseudomonas aeruginosa harboring Verona-integron-encoded metallo-β-lactamase were identified in a city in western Texas, USA. A faucet contaminated with the organism, identified through environmental sampling, in a specialty care room was the likely source for infection in a subset of patients.

OBJECTIVES: We examined COVID-19 vaccination status, intention, and hesitancy and the effects of five strategies to increase the willingness of unvaccinated adults (≥18 years) to get a COVID vaccine. METHODS: Online surveys were conducted between October 1-17, 2020 (N = 14,946), December 4-16, 2020 (N = 15,229), April 8-22, 2021 (N = 14,557), June 17-July 6, 2021 (N = 30,857), and September 3-October 4, 2021 (N = 33,088) with an internet-based, non-probability opt-in sample of U.S. adults matching demographic quotas. Respondents were asked about current COVID-19 vaccination status, intention and hesitancy to get vaccinated, and reasons for vaccine hesitancy. Unvaccinated respondents were assigned to treatment groups to test the effect of five strategies (endorsements, changing social restrictions, financial incentives, vaccine requirements for certain activities, and vaccine requirements for work). Chi-square tests of independence were performed to detect differences in the response distributions. RESULTS: Willingness to be vaccinated (defined as being vaccinated or planning to be) increased over time from 47.6 % in October 2020 to 81.1 % in October 2021. By October 2021, across most demographic groups, over 75 % of survey respondents had been or planned to be vaccinated. In terms of strategies: (1) endorsements had no positive effect, (2) relaxing the need for masks and social distancing increased Intention to Get Vaccinated (IGV) by 6.4 % (p < 0.01), (3) offering financial incentives increased the IGV between 12.3 and 18.9 % (p <.001), (4) vaccine requirements for attending sporting events or traveling increased IGV by 7.8 % and 9.1 %, respectively (p = 0.02), and vaccine requirement for work increased IGV by 35.4 %. The leading causes (not mutually exclusive) for hesitancy were concerns regarding vaccine safety (52.5 %) or side effects (51.6 %), trust in the government's motives (41.0 %), and concerns about vaccine effectiveness (37.6 %). CONCLUSIONS: These findings suggest that multiple strategies may be effective and needed to increase COVID-19 vaccination among hesitant adults during the pandemic.

The CDC's Emerging Infections Program (EIP) conducted population- and laboratory-based surveillance of US carbapenem-resistant Pseudomonas aeruginosa (CRPA) from 2016 through 2018. To characterize the pathotype, 1,019 isolates collected through this project underwent antimicrobial susceptibility testing and whole-genome sequencing. Sequenced genomes were classified using the seven-gene multilocus sequence typing (MLST) scheme and a core genome (cg)MLST scheme was used to determine phylogeny. Both chromosomal and horizontally transmitted mechanisms of carbapenem resistance were assessed. There were 336 sequence types (STs) among the 1,019 sequenced genomes, and the genomes varied by an average of 84.7% of the cgMLST alleles used. Mutations associated with dysfunction of the porin OprD were found in 888 (87.1%) of the genomes and were correlated with carbapenem resistance, and a machine learning model incorporating hundreds of genetic variations among the chromosomal mechanisms of resistance was able to classify resistant genomes. While only 7 (0.1%) isolates harbored carbapenemase genes, 66 (6.5%) had acquired non-carbapenemase β-lactamase genes, and these were more likely to have OprD dysfunction and be resistant to all carbapenems tested. The genetic diversity demonstrates that the pathotype includes a variety of strains, and clones previously identified as high-risk make up only a minority of CRPA strains in the United States. The increased carbapenem resistance in isolates with acquired non-carbapenemase β-lactamase genes suggests that horizontally transmitted mechanisms aside from carbapenemases themselves may be important drivers of the spread of carbapenem resistance in P. aeruginosa.

Coffee production workers are exposed to complex mixtures of gases, dust, and vapors, including the known respiratory toxins, diacetyl, and 2,3-pentanedione, which occur naturally during coffee roasting and are also present in flavorings used to flavor coffee. This study evaluated the associations of these two -diketones with lung function measures in coffee production workers. Workers completed questionnaires, and their lung function was assessed by spirometry and impulse oscillometry (IOS). Personal exposures to diacetyl, 2,3-pentanedione, and their sum (Sum(DA+PD)) were assigned to participants, and metrics of the highest 95th percentile (P95), cumulative, and average exposure were calculated. Linear and logistic regression models for continuous and binary/polytomous outcomes, respectively, were used to explore exposure-response relationships adjusting for age, body mass index, tenure, height, sex, smoking status, race, or allergic status. Decrements in percent predicted forced expiratory volume in 1 second (ppFEV(1)) and forced vital capacity (ppFVC) were associated with the highest-P95 exposures to 2,3-pentanedione and Sum(DA+PD). Among flavoring workers, larger decrements in ppFEV(1) and ppFVC were associated with highest-P95 exposures to diacetyl, 2,3-pentanedione, and Sum(DA+PD). Abnormal FEV(1), FVC, and restrictive spirometric patterns were associated with the highest-P95, cumulative, and average exposures for all -diketone metrics; some of these associations were also present among flavoring and non-flavoring workers. The combined category of small and peripheral airways plus small and large airways abnormalities on IOS had elevated odds for highest-P95 exposure to -diketones. These results may be affected by the small sample size, few cases of abnormal spirometry, and the healthy worker effect. Associations between lung function abnormalities and exposure to -diketones suggest it may be prudent to consider exposure controls in both flavoring and non-flavoring settings.

Exposure to elevated levels of diacetyl in flavoring and microwave popcorn production has been associated with respiratory impairment among workers including from a severe lung disease known as obliterative bronchiolitis. Laboratory studies demonstrate damage to the respiratory tract in rodents exposed to either diacetyl or the related alpha-diketone 2,3-pentanedione. Respiratory tract damage includes the development of obliterative bronchiolitis-like changes in the lungs of rats repeatedly inhaling either diacetyl or 2,3-pentanedione. In one flavored coffee processing facility, current workers who spent time in higher diacetyl and 2,3-pentanedione areas had lower lung function values, while five former flavoring room workers were diagnosed with obliterative bronchiolitis. In that and other coffee roasting and packaging facilities, grinding roasted coffee beans has been identified as contributing to elevated levels of diacetyl and 2,3-pentanedione. To reduce worker exposures, employers can take various actions to control exposures according to the hierarchy of controls. Because elimination or substitution is not applicable to coffee production facilities not using flavorings, use of engineering controls to control exposures at their source is especially important. This work demonstrates the use of temporary ventilated enclosures around grinding equipment in a single coffee roasting and packaging facility to mitigate diacetyl and 2,3-pentanedione emissions from grinding equipment to the main production space. Concentrations of diacetyl and 2,3-pentanedione were measured in various locations throughout the main production space as well as inside and outside of ventilated enclosures to evaluate the effect of the enclosures on exposures. Diacetyl and 2,3-pentanedione concentrations outside one grinder enclosure decreased by 95 and 92%, respectively, despite ground coffee production increasing by 12%, after the enclosure was installed. Outside a second enclosure, diacetyl and 2,3-pentanedione concentrations both decreased 84%, greater than the 33% decrease in ground coffee production after installation. Temporary ventilated enclosures used as engineering control measures in this study effectively reduced emissions of diacetyl and 2,3-pentanedione at the source in this facility. These findings motivated management to explore options with a grinding equipment manufacturer to permanently ventilate their grinders to reduce emissions of diacetyl and 2,3-pentanedione.

OBJECTIVES: To determine whether engineering controls and respiratory protection had measurable short-term impact on indium exposure and respiratory health among current indium-tin oxide production and reclamation facility workers. METHODS: We documented engineering controls implemented following our 2012 evaluation and recorded respirator use in 2012 and 2014. We measured respirable indium (In(resp)) and plasma indium (In(P)) in 2012 and 2014, and calculated change in In(resp) (∆In(resp)) and In(P) (∆In(P)) by the 13 departments. We assessed symptoms, lung function, serum biomarkers of interstitial lung disease (Krebs von den Lungen (KL)-6 and surfactant protein (SP)-D) and chest high-resolution CT at both time points and evaluated workers who participated in both 2012 and 2014 for changes in health outcomes (new, worsened or improved). RESULTS: Engineering controls included installation of local exhaust ventilation in both grinding departments (Rotary and Planar) and isolation of the Reclaim department. Respiratory protection increased in most (77%) departments. ∆In(P) and ∆In(resp) often changed in parallel by department. Among 62 workers participating in both 2012 and 2014, 18 (29%) had new or worsening chest symptoms and 2 (3%) had functional decline in lung function or radiographic progression, but average KL-6 and SP-D concentrations decreased, and no cases of clinical indium lung disease were recognised. CONCLUSIONS: Increased engineering controls and respiratory protection can lead to decreased In(resp), In(P) and biomarkers of interstitial lung disease among workers in 2 years. Ongoing medical monitoring of indium-exposed workers to confirm the longer-term effectiveness of preventive measures is warranted.

Genomic surveillance is a critical tool for tracking emerging variants of SARS-CoV-2 (the virus that causes COVID-19), which can exhibit characteristics that potentially affect public health and clinical interventions, including increased transmissibility, illness severity, and capacity for immune escape. During June 2021-January 2022, CDC expanded genomic surveillance data sources to incorporate sequence data from public repositories to produce weighted estimates of variant proportions at the jurisdiction level and refined analytic methods to enhance the timeliness and accuracy of national and regional variant proportion estimates. These changes also allowed for more comprehensive variant proportion estimation at the jurisdictional level (i.e., U.S. state, district, territory, and freely associated state). The data in this report are a summary of findings of recent proportions of circulating variants that are updated weekly on CDC's COVID Data Tracker website to enable timely public health action.(†) The SARS-CoV-2 Delta (B.1.617.2 and AY sublineages) variant rose from 1% to >50% of viral lineages circulating nationally during 8 weeks, from May 1-June 26, 2021. Delta-associated infections remained predominant until being rapidly overtaken by infections associated with the Omicron (B.1.1.529 and BA sublineages) variant in December 2021, when Omicron increased from 1% to >50% of circulating viral lineages during a 2-week period. As of the week ending January 22, 2022, Omicron was estimated to account for 99.2% (95% CI = 99.0%-99.5%) of SARS-CoV-2 infections nationwide, and Delta for 0.7% (95% CI = 0.5%-1.0%). The dynamic landscape of SARS-CoV-2 variants in 2021, including Delta- and Omicron-driven resurgences of SARS-CoV-2 transmission across the United States, underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.

OBJECTIVE: The incidence of infections from extended-spectrum β-lactamase (ESBL)-producing Enterobacterales (ESBL-E) is increasing in the United States. We describe the epidemiology of ESBL-E at 5 Emerging Infections Program (EIP) sites. METHODS: During October-December 2017, we piloted active laboratory- and population-based (New York, New Mexico, Tennessee) or sentinel (Colorado, Georgia) ESBL-E surveillance. An incident case was the first isolation from normally sterile body sites or urine of Escherichia coli or Klebsiella pneumoniae/oxytoca resistant to ≥1 extended-spectrum cephalosporin and nonresistant to all carbapenems tested at a clinical laboratory from a surveillance area resident in a 30-day period. Demographic and clinical data were obtained from medical records. The Centers for Disease Control and Prevention (CDC) performed reference antimicrobial susceptibility testing and whole-genome sequencing on a convenience sample of case isolates. RESULTS: We identified 884 incident cases. The estimated annual incidence in sites conducting population-based surveillance was 199.7 per 100,000 population. Overall, 800 isolates (96%) were from urine, and 790 (89%) were E. coli. Also, 393 cases (47%) were community-associated. Among 136 isolates (15%) tested at the CDC, 122 (90%) met the surveillance definition phenotype; 114 (93%) of 122 were shown to be ESBL producers by clavulanate testing. In total, 111 (97%) of confirmed ESBL producers harbored a blaCTX-M gene. Among ESBL-producing E. coli isolates, 52 (54%) were ST131; 44% of these cases were community associated. CONCLUSIONS: The burden of ESBL-E was high across surveillance sites, with nearly half of cases acquired in the community. EIP has implemented ongoing ESBL-E surveillance to inform prevention efforts, particularly in the community and to watch for the emergence of new ESBL-E strains.

Carbapenem-resistant Pseudomonas aeruginosa (CRPA) producing the Verona integron‒encoded metallo-β-lactamase (VIM) are highly antimicrobial drug-resistant pathogens that are uncommon in the United States. We investigated the source of VIM-CRPA among US medical tourists who underwent bariatric surgery in Tijuana, Mexico. Cases were defined as isolation of VIM-CRPA or CRPA from a patient who had an elective invasive medical procedure in Mexico during January 2018‒December 2019 and within 45 days before specimen collection. Whole-genome sequencing of isolates was performed. Thirty-eight case-patients were identified in 18 states; 31 were operated on by surgeon 1, most frequently at facility A (27/31 patients). Whole-genome sequencing identified isolates linked to surgeon 1 were closely related and distinct from isolates linked to other surgeons in Tijuana. Facility A closed in March 2019. US patients and providers should acknowledge the risk for colonization or infection after medical tourism with highly drug-resistant pathogens uncommon in the United States.

OBJECTIVE: To establish a pathoepidemiological model to evaluate the role of SARS-CoV-2 infection in the first 10 companion animals that died while infected with SARS-CoV-2 in the US. ANIMALS: 10 cats and dogs that tested positive for SARS-CoV-2 and died or were euthanized in the US between March 2020 and January 2021. PROCEDURES: A standardized algorithm was developed to direct case investigations, determine the necessity of certain diagnostic procedures, and evaluate the role, if any, that SARS-CoV-2 infection played in the animals' course of disease and death. Using clinical and diagnostic information collected by state animal health officials, state public health veterinarians, and other state and local partners, this algorithm was applied to each animal case. RESULTS: SARS-CoV-2 was an incidental finding in 8 animals, was suspected to have contributed to the severity of clinical signs leading to euthanasia in 1 dog, and was the primary reason for death for 1 cat. CONCLUSIONS AND CLINICAL RELEVANCE: This report provides the global community with a standardized process for directing case investigations, determining the necessity of certain diagnostic procedures, and determining the clinical significance of SARS-CoV-2 infections in animals with fatal outcomes and provides evidence that SARS-CoV-2 can, in rare circumstances, cause or contribute to death in pets.

Carbapenemase gene-positive (CP) Gram-negative bacilli are of significant clinical and public health concern. Their rapid detection and containment are critical to preventing their spread and additional infections they can cause. To this end, CDC developed the Antibiotic Resistance Laboratory Network (AR Lab Network), in which public health laboratories across all 50 states, several cities, and Puerto Rico characterize clinical isolates of carbapenem-resistant Enterobacterales (CRE), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB), and conduct colonization screens to detect the presence of mobile carbapenemase genes. In its first three years, the AR Lab Network tested 76,887 isolates and 31,001 rectal swab colonization screens. Targeted carbapenemase genes (bla(KPC), bla(NDM), bla(OXA-48-like), bla(VIM), or bla(IMP)) were detected by PCR in 35% of CRE, 2% of CRPA, <1% of CRAB, and 8% of colonization screens tested, respectively. bla(KPC) and bla(VIM) were the most common CP-CRE and CP-CRPA, respectively, but regional differences in the frequency of carbapenemase genes detected were apparent. In CRE and CRPA isolates tested for carbapenemase production and the presence of the targeted genes, 97% had concordant results; 3% of CRE and 2% of CRPA were carbapenemase production-positive but PCR-negative for those genes. Isolates harboring bla(NDM) showed the highest frequency of resistance across the carbapenems tested and those harboring bla(IMP) and bla(OXA-48-like) genes showed the lowest frequency of carbapenem resistance. The AR Lab Network provides a national snapshot of rare and emerging carbapenemase genes, delivering data to inform public health actions to limit the spread of these antibiotic resistance threats.

Reports of organisms harboring multiple carbapenemase genes have increased since 2010. During October 2012-April 2019, the Centers for Disease Control and Prevention documented 151 of these isolates from 100 patients in the United States. Possible risk factors included recent history of international travel, international inpatient healthcare, and solid organ or bone marrow transplantation.

MOTIVATION: Tools used to identify genes in microbial sequences using a reference database generally report matches as a percent identity, which can be difficult to interpret in cases with <100%sequence identity, as changes to specific amino acids can have dramatic effects on protein function, such as when they occur in substrate binding regions or enzyme active sites, which in turn can have dramatic effects on phenotypes like antimicrobial resistance or virulence. RESULTS: Here we present GAMMA, an open-source tool for Gene Allele Mutation Microbial Assessment, which uses protein coding-level identity to make gene calls from any gene database and generates a classification (e.g., mutant, truncation) and translated annotation (e.g., Y190S mutation, truncation at residue 110) for these calls. GAMMA accurately called antimicrobial resistance genes from a large set of genomes faster than three other tools. It can also be used with any gene database, as we demonstrated by identifying virulence genes in the same genome set. Because of its speed and flexibility, GAMMA can be used to rapidly find and annotate any gene matches of interest in microbial sequencing data. AVAILABILITY: GAMMA is freely available as a Bioconda package (https://bioconda.github.io/recipes/gamma/README.html) and as a command line script (https://github.com/rastanton/GAMMA). SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Infections caused by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli are a significant cause of morbidity and healthcare costs. Globally, the prevailing clonal type is ST131 in association with the blaCTX-M-15 β-lactamase gene. However, other ESBLs such as blaCTX-M-14 and blaCTX-M-27 can also be prevalent in some regions. We identified ST38 ESBL-producing E. coli from different regions in the US which carry blaCTX-M-27 embedded on two distinct plasmid types, suggesting the potential emergence of new ESBL lineages.

BACKGROUND: Determine the overall, sex-, and racially/ethnically-appropriate population-level cotinine and total nicotine equivalents (TNE-2, the molar sum of the two major nicotine metabolites) cut-points to distinguish tobacco users from non-users across multiple definitions of use (e.g., exclusive vs. polytobacco, and daily vs. non-daily). METHODS: Using Wave 1 (2013-2014) of the U.S. Population Assessment of Tobacco and Health (PATH) Study, we conducted weighted Receiver Operating Curve (ROC) analysis to determine the optimal urinary cotinine and TNE-2 cut-points, stratified by sex and race/ethnicity. RESULTS: For past 30-day exclusive cigarette users, the cotinine cut-point that distinguished them from non-users was 40.5 ng/mL, with considerable variation by sex (male: 22.2 ng/mL; female: 43.1 ng/mL) and between racial/ethnic groups (non-Hispanic other: 5.2 ng/mL; non-Hispanic black: 297.0 ng/mL). A similar, but attenuated, pattern emerged when assessing polytobacco cigarette users (overall cut-point= 39.1 ng/mL, range= 5.5 ng/mL- 80.4 ng/mL) and any tobacco users (overall cut-point= 39.1 ng/mL, range= 4.8 ng/mL- 40.0 ng/mL). Using TNE-2, which is less impacted by racial differences in nicotine metabolism, produced a comparable pattern of results although reduced the range magnitude. CONCLUSIONS: Due to similar frequency of cigarette use among polytobacco users, overall cut-points for exclusive cigarette use were not substantially different from cut-points that included polytobacco cigarette use or any tobacco use. Results revealed important differences in sex and race/ethnicity appropriate cut-points when evaluating tobacco use status and established novel urinary TNE-2 cut-points. IMPACT: These cut-points may be used for biochemical verification of self-reported tobacco use in epidemiologic studies and clinical trials.

INTRODUCTION: Concurrent use of tobacco cigarettes and e-cigarettes ("dual use") is common among tobacco users. Little is known about differences in demographics and toxicant exposure among subsets of dual users. AIMS AND METHODS: We analyzed data from adult dual users (current every/some day users of tobacco cigarettes and e-cigarettes, n = 792) included in the PATH Study Wave 1 (2013-2014) and provided urine samples. Samples were analyzed for biomarkers of exposure to nicotine and selected toxicants (tobacco-specific nitrosamine NNK [NNAL], lead, cadmium, naphthalene [2-naphthol], pyrene [1-hydroxypyrene], acrylonitrile [CYMA], acrolein [CEMA], and acrylamide [AAMA]). Subsets of dual users were compared on demographic, behavioral, and biomarker measures to exclusive cigarette smokers (n = 2411) and exclusive e-cigarette users (n = 247). RESULTS: Most dual users were predominant cigarette smokers (70%), followed by daily dual users (13%), non-daily concurrent dual users (10%), and predominant vapers (7%). Dual users who smoked daily showed significantly higher biomarker concentrations compared with those who did not smoke daily. Patterns of e-cigarette use had little effect on toxicant exposure. Dual users with high toxicant exposure were generally older, female, and smoked more cigarettes per day. Dual users who had low levels of biomarkers of exposure were generally younger, male, and smoked non-daily. CONCLUSIONS: In 2013-2014, most dual users smoked cigarettes daily and used e-cigarettes occasionally. Cigarette smoking appears to be the primary driver of toxicant exposure among dual users, with little-to-no effect of e-cigarette use on biomarker levels. Results reinforce the need for dual users to stop smoking tobacco cigarettes to reduce toxicant exposure. IMPLICATIONS: With considerable dual use of tobacco cigarettes and e-cigarettes in the United States, it is important to understand differences in toxicant exposure among subsets of dual users, and how these differences align with user demographics. Findings suggest most dual users smoke daily and use e-cigarettes intermittently. Low exposure to toxicants was most common among younger users, males, and intermittent smokers; high exposure to toxicants was most common among older users, females, and heavier cigarette smokers. Results underscore the heterogeneity occurring within dual users, and the need to quit smoking cigarettes completely in order to reduce toxicant exposure.

PURPOSE OF REVIEW: To examine respiratory and skin diseases that occur among workers exposed to metalworking fluids (MWFs) used during machining processes. RECENT FINDINGS: Five cases of a severe and previously unrecognized lung disease characterized by B-cell bronchiolitis and alveolar ductitis with emphysema (BADE) were identified among workers at a machining facility that used MWFs, although MWF exposure could not be confirmed as the etiology. In the United Kingdom, MWF is now the predominant cause of occupational hypersensitivity pneumonitis (HP). Under continuous conditions associated with respiratory disease outbreaks, over a working lifetime of 45 years, workers exposed to MWF at 0.1 mg/m3 are estimated to have a 45.3% risk of acquiring HP or occupational asthma under outbreak conditions and a 3.0% risk assuming outbreak conditions exist in 5% of MWF environments. In addition to respiratory outcomes, skin diseases such as allergic and irritant contact dermatitis persist as frequent causes of occupational disease following MWF exposure. SUMMARY: Healthcare providers need to consider MWF exposure as a potential cause for work-related respiratory and skin diseases. Additional work is necessary to more definitively characterize any potential association between MWF exposures and BADE. Medical surveillance should be implemented for workers regularly exposed to MWF.

Roasted coffee and many coffee flavorings emit volatile organic compounds (VOCs) including diacetyl and 2,3-pentanedione. Exposures to VOCs during roasting, packaging, grinding, and flavoring coffee can negatively impact the respiratory health of workers. Inhalational exposures to diacetyl and 2,3-pentanedione can cause obliterative bronchiolitis. This study summarizes exposures to and emissions of VOCs in 17 coffee roasting and packaging facilities that included 10 caf&#233;s. We collected 415 personal and 760 area full-shift, and 606 personal task-based air samples for diacetyl, 2,3-pentanedione, 2,3-hexanedione, and acetoin using silica gel tubes. We also collected 296 instantaneous activity and 312 instantaneous source air measurements for 18 VOCs using evacuated canisters. The highest personal full-shift exposure in part per billion (ppb) to diacetyl [geometric mean (GM) 21 ppb; 95th percentile (P95) 79 ppb] and 2,3-pentanedione (GM 15 ppb; P95 52 ppb) were measured for production workers in flavored coffee production areas. These workers also had the highest percentage of measurements above the NIOSH Recommended Exposure Limit (REL) for diacetyl (95%) and 2,3-pentanedione (77%). Personal exposures to diacetyl (GM 0.9 ppb; P95 6.0 ppb) and 2,3-pentanedione (GM 0.7 ppb; P95 4.4 ppb) were the lowest for non-production workers of facilities that did not flavor coffee. Job groups with the highest personal full-shift exposures to diacetyl and 2,3-pentanedione were flavoring workers (GM 34 and 38 ppb), packaging workers (GM 27 and 19 ppb) and grinder operator (GM 26 and 22 ppb), respectively, in flavored coffee facilities, and packaging workers (GM 8.0 and 4.4 ppb) and production workers (GM 6.3 and 4.6 ppb) in non-flavored coffee facilities. Baristas in caf&#233;s had mean full-shift exposures below the RELs (GM 4.1 ppb diacetyl; GM 4.6 ppb 2,3-pentanedione). The tasks, activities, and sources associated with flavoring in flavored coffee facilities and grinding in non-flavored coffee facilities, had some of the highest GM and P95 estimates for both diacetyl and 2,3-pentanedione. Controlling emissions at grinding machines and flavoring areas and isolating higher exposure areas (e.g., flavoring, grinding, and packaging areas) from the main production space and from administrative or non-production spaces is essential for maintaining exposure control.

Hookah smoking has become common in the USA, especially among young adults. This study measured biomarkers of exposure to known tobacco product toxicants in a population-based sample of exclusive, established hookah users. Urinary biomarker data from 1753 adults in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study were used to compare geometric mean concentrations of biomarkers of exposure in exclusive, established past 30-day hookah users to never users of tobacco. Geometric mean ratios were calculated comparing hookah user groups with never users adjusting for age, sex, race/ethnicity, education, past 30-day marijuana use, secondhand smoke exposure and creatinine. Past 30-day hookah users (n = 98) had 10.6 times the urinary cotinine level of never tobacco users. Compared to never tobacco users, past 30-day hookah users had 2.3 times the level of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1.3 times higher polycyclic aromatic hydrocarbons (PAHs) 3-hydroxyfluorene and 1-hydroxypyrene, 1.8 times higher levels of acrylonitrile, 1.3 times higher levels of acrylamide, and 1.2 times higher levels of acrolein exposure. These data indicate that hookah use is a significant source of exposure to nicotine, carcinogens, and respiratory toxicants.

INTRODUCTION: Workers' exposure to metalworking fluid (MWF) has been associated with respiratory disease. As part of a public health investigation of a manufacturing facility, we performed paired environmental and human sampling to evaluate cross-pollination of microbes between environment and host and possible effects on lung pathology present among workers. METHODS: Workplace environmental microbiota was evaluated in air and MWF samples. Human microbiota was evaluated in lung tissue samples from workers with respiratory symptoms found to have lymphocytic bronchiolitis and alveolar ductitis with B-cell follicles and emphysema, lung tissue controls, and in skin, nasal and oral samples from 302 workers from different areas of the facility. In vitro effects of MWF exposure on murine B-cells were assessed. RESULTS: Increased similarity of microbial composition was found between MWF samples and lung tissue samples of case workers compared to controls. Among workers in different locations within the facility, those that worked in machine shop area had skin, nasal and oral microbiota more closely related to the microbiota present in MWF samples. Lung samples from four index cases, and skin and nasal samples from workers in machine shop area were enriched with Pseudomonas, the dominant taxa in MWF. Exposure to used MWF stimulated murine B-cell proliferation in vitro, a hallmark cell subtype found in pathology of index cases. CONCLUSIONS: Evaluation of a manufacturing facility with a cluster of workers with respiratory disease supports cross-pollination of microbes from MWF to humans and suggests the potential for exposure to these microbes to be a health hazard.

BACKGROUND: Colonisation with Streptococcus pneumoniae can lead to invasive pneumococcal disease and pneumonia. Pneumococcal acquisition and prevalence of colonisation are high in children. In older adults, a population susceptible to pneumococcal disease, colonisation prevalence is reported to be lower, but studies are heterogeneous. METHODS: This is a systematic review and meta-analysis of prevalence of, and risk factors for, pneumococcal colonisation in adults ≥ 60 years of age (PROSPERO #42016036891). We identified peer-reviewed studies reporting the prevalence of S. pneumoniae colonisation using MEDLINE and EMBASE (until April 2016), excluding studies of acute disease. Participant-level data on risk factors were sought from each study. FINDINGS: Of 2202 studies screened, 29 were analysable: 18 provided participant-level data (representing 6290 participants). Prevalence of detected pneumococcal colonisation was 0-39% by conventional culture methods and 3-23% by molecular methods. In a multivariate analysis, colonisation was higher in persons from nursing facilities compared with the community (odds ratio (OR) 2•30, 95% CI 1•26-4•21 and OR 7•72, 95% CI 1•15-51•85, respectively), in those who were currently smoking (OR 1•69, 95% CI 1•12-2•53) or those who had regular contact with children (OR 1•93, 95%CI 1•27-2•93). Persons living in urban areas had significantly lower carriage prevalence (OR 0•43, 95%CI 0•27-0•70). INTERPRETATION: Overall prevalence of pneumococcal colonisation in older adults was higher than expected but varied by risk factors. Future studies should further explore risk factors for colonisation, to highlight targets for focussed intervention such as pneumococcal vaccination of high-risk groups. FUNDING: No funding was required.

Pseudomonas aeruginosa is an opportunistic human pathogen that frequently causes healthcare-associated infections (HAIs). Due to its metabolic diversity and ability to form biofilms, this gram negative, non-fermenter can persist in the healthcare environment, which can lead to prolonged HAI outbreaks. We describe the creation of a core genome MLST (cgMLST) scheme to provide a stable platform for the rapid comparison of P. aeruginosa isolates using whole genome sequencing (WGS) data. We used a diverse set of 58 complete P. aeruginosa genomes to curate a set of 4400 core genes found in each isolate, representing approximately 65% of the average genome size. We then expanded the alleles for each gene using 1991 contig-level genome sequences. The scheme was used to analyze genomes from four historical HAI outbreaks to compare the phylogenies generated using cgMLST to those of other means (traditional MLST, PFGE, and SNV analysis). The cgMLST scheme provides sufficient resolution for analyzing individual outbreaks, as well as the stability for comparisons across a variety of isolates encountered in surveillance studies, making it a valuable tool for the rapid analysis of P. aeruginosa genomes.

Brodifacoum, a long-acting vitamin K epoxide cycle antagonist, is a rodenticide encountered in intentional ingestions and as a contaminant of some synthetic cannabinoid products.1 Serious brodifacoum poisoning is characterized by life-threatening hemorrhage. | | Brodifacoum poisoning is treated with vitamin K1, but the treatment duration is variable, and thus management of the condition is challenging. Case reports indicate that the brodifacoum elimination half-life ranges from 16 to 62 days.2,3 On the basis of clinical experience, we propose discontinuing vitamin K1 treatment when a patient’s blood brodifacoum concentration is less than 10 ng per milliliter.3-5 In clinical practice, treatment has most often been discontinued at an arbitrary time, with the subsequent coagulation profile monitored. If the coagulation profile becomes abnormal, treatment is resumed. Another strategy is to discontinue treatment at an arbitrary time but monitor the activity of clotting factors; a decline in activity indicates the need to restart therapy. A third strategy is to exploit a consequence of vitamin K1 treatment — increased accumulation of vitamin K epoxide relative to vitamin K quinol, assessed by monitoring the ratio of vitamin K epoxide to vitamin K quinol. Vitamin K1 therapy then may be stopped when this ratio is less than 0.1.2 These strategies are all limited by the necessity of periodic blood-specimen collection, which puts the patient at risk for recurrent bleeding when treatment is withheld to assess periodic coagulation profiles, as well as by the requirement for specialized reference laboratory testing (e.g., measurement of active clotting-factor activity and vitamin K1 oxidation state) with a rapid turnaround time.