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Gastrointestinal parasites have diverse life cycles that can involve people, animals, and the environment (e.g., water and soil), demonstrating the utility of One Health frameworks in characterizing infection risk. Kosumpee Forest Park (Thailand) is home to a dense population of long-tailed macaques (Macaca fascicularis) that frequently interact with tourists and local residents. Our study investigated the presence of zoonotic parasites, and barriers to healthy coexistence by conducting stool analysis on macaques (N = 102) and people (N = 115), and by examining risk factors for infection with a household questionnaire (N = 95). Overall, 44% of macaques and 12% of people were infected with one or more gastrointestinal helminths, including Strongyloides spp., Ascaris spp., and Trichuris sp. An adults-only generalized linear mixed model identified three factors significantly associated with human infection: household size, occupational exposure, and contact with macaque feces at home. Participants identified both advantages and disadvantages to living in close contact with macaques, suggesting that interventions to improve human and animal health in Kosumpee Forest Park would be welcome.

OBJECTIVES: Noise induced hearing loss (NIHL) remains one of the most prevalent occupational diseases. Occupational hearing conservation programs (HCPs) can reduce the risk of NIHL, but there remains no consensus on assessing HCP effectiveness. We conducted a multi-site, mixed-method assessment of HCP programs. METHODS: At thirteen manufacturing plants, we performed assessments, including interviews with program staff and worker focus groups and surveys. We analyzed the association between these assessments and age-corrected NIHL rates. RESULTS: Only a few items from the HCP staff interviews correlated with NIHL rates. For the employee survey, management commitment to NIHL prevention and being counseled about NIHL were strongly associated with NIHL rates. CONCLUSION: Management commitment and counseling of workers about NIHL may be key factors in program effectiveness. A combination of qualitative and quantitative methods appears to be useful for assessing HCPs.

Most emerging infectious diseases are zoonotic in origin, with wildlife a frequent source of zoonotic disease events. Although individuals with extensive wildlife contact may be at the greatest risk of contracting novel infectious agents, the occupational risk of those working closely with wildlife has not been well studied. This study assessed the occupational exposures among wildlife health professionals working in multiple countries worldwide. An occupational risk survey of past and present exposures was developed and administered online in a confidential manner to wildlife workers recruited through an ongoing international wildlife pathogen surveillance project. Surveys were completed by 71 participants in 14 countries. Significant lifetime exposures reported included bites from bats and rodents and touching dead animals. Completion of training in occupational safety was reported by 75% of respondents. While gloves were used for most tasks, use of N95 respirators and other personal protective equipment varied by task. Eighty percent of workers reported rabies vaccination. Some respondents indicated interest in enhanced occupational health services targeting their unique needs. Wildlife workers represent an occupational population at risk of zoonotic infection and injury. Enhanced occupational health services targeting wildlife workers could reduce the risk and sequelae of zoonotic exposure and infection.

Overexpression of aurora kinase A (AURKA) confers a poor prognosis in patients with urothelial carcinoma of the bladder. The prognostic value of high aurora kinase B (AURKB) expression in local bladder cancer is not well defined, and whether the prognostic value of either AURKA or AURKB is affected by the use of chemotherapy is unknown. We sought to characterize the impact of high AURKA and AURKB expression on clinical outcome in patients with muscle-invasive bladder cancer (MIBC) who received neoadjuvant chemotherapy (NAC).Immunohistochemistry for AURKA and AURKB was performed on pretreatment diagnostic transurethral resection of bladder tumor (TURBT) and matched cystectomy specimens in 50 subjects with MIBC who received NAC. Receiver operator characteristic curves (ROC) were calculated to assess the impact of AURKA and AURKB expression on pathologic response rate. Kaplan-Meier techniques and Cox proportional hazards models were used to assess the association with relapse-free survival (RFS) and overall survival (OS).Twenty-two of 50 [44%] patients had residual muscle-invasive (ypT2-4) urothelial carcinoma after NAC. Neither baseline tumor expression of AURKA (ROC = 0.57, P = 0.46) nor AURKB (ROC = 0.56, P = 0.87) predicted for ypT2-4 status. However, baseline expression of AURKA above the 75th percentile for this cohort was associated with an inferior RFS, (HR = 3.88, P = 0.008) and OS, (HR = 6.10, P0.001). Similar trends for worse survival outcomes were also observed for high AURKB levels (RFS, [HR = 2.2, P = 0.13] and OS, (HR = 2.25, P = 0.09).High baseline tumor AURKA and AURKB expression identified MIBC patients with inferior RFS and OS despite the use of NAC and may identify patients who should be prioritized for clinical trial enrollment rather than standard cisplatin-based chemotherapy.

Objective: We assessed the reliability of a hearing risk factor screening survey used by hearing conservation programmes for noise-exposed workers. Design: We compared workers’ answers from the screening survey to their answers to a confidential research questionnaire regarding hearing loss risk factors. We calculated kappa statistics to test the correlation between yes/no questions in the research questionnaire compared to answers from 1 and 5 years of screening surveys. Study sample: We compared the screening survey and research questionnaire answers of 274 aluminum plant workers. Results: Most of the questions in the in-company screening survey showed fair to moderate agreement with the research questionnaire (kappa range: −0.02, 0.57). Workers’ answers to the screening survey had better correlation with the research questionnaire when we compared 5 years of screening answers. For nearly all questions, workers were more likely to respond affirmatively on the research questionnaire than the screening survey. Conclusions: Hearing conservation programmes should be aware that workers may underreport hearing loss risk factors and functional hearing status on an audiometric screening survey. Validating company screening tools could help provide more accurate information on hearing loss and risk factors.

We report on a study conducted in Guangdong Province, China, to characterize behaviors and perceptions associated with transmission of pathogens with pandemic potential in highly exposed human populations at the animal-human interface. A risk factor/exposure survey was administered to individuals with high levels of exposure to wildlife. Serological testing was performed to evaluate prior infection with several wildlife viral pathogens. Follow up serology was performed on a subset of the cohort as well as close contacts of individuals. 1,312 individuals were enrolled in the study. Contact with a wide range of wildlife species was reported in both occupational and occasional contexts. The overall proportion of individuals seropositive to any of the tested wildlife pathogens was approximately 4.0%. However, persons employed as butchers demonstrated a seropositivity of 9.0% to at least one pathogen of interest. By contrast, individuals working as hunters had lower rates of seropositivity. Among the study population, a number of other behaviors showed correlation with seropositivity, including contact with particular wildlife species such as field rats. These results demonstrate the need to further explore zoonotic risks of particular activities regarding wildlife contact, and to better understand risks of persons working as butchers with wildlife species.

Dairy farming involves frequent contact among animals, workers and farm environments. To explore the Staphylococcus spp. diversity that occurs on dairy farms, a pilot study sampled dairy workers, cows and the farm environments from five farms, two organic and three conventional farms, in Washington State. Samples were taken from the nares and hands of consenting workers (n = 24), udders and nares of selected cows (n = 25) and representative environmental surfaces (n = 96) from each farm. To increase diversity of the Staphylococcus spp. characterized, five distinct colonies were selected from each sample for identification with 16S analysis. A total of 198 staphylococci were characterized representing 19 different Staphylococcus spp. The diversity of species ranged from 9-15 Staphylococcus spp./farm with no difference between conventional and organic farms. S. haemolyticus [n = 60 isolates] was the most common species and was isolated from all farms and from cows, humans and environmental samples. Whole genome sequencing of selected S. haemolyticus found no genetically related isolates among human, animal and environmental samples within the same farm. S. epidermidis, S. saprophyticus, S. sciuri and S. xylosus were also found in ≥1 farms from human, animal and environmental samples.

Background: Little is known about the environmental and public health impact of unconventional natural gas extraction activities, including hydraulic fracturing, that occur near residential areas. Objectives: Our aim was to assess the relationship between household proximity to natural gas wells and reported health symptoms. Methods: We conducted a hypothesis-generating health symptom survey of 492 persons in 180 randomly selected households with ground-fed wells in an area of active natural gas drilling. Gas well proximity for each household was compared with the prevalence and frequency of reported dermal, respiratory, gastrointestinal, cardiovascular, and neurological symptoms. Results: The number of reported health symptoms per person was higher among residents living < 1 km (mean ± SD, 3.27 ± 3.72) compared with > 2 km from the nearest gas well (mean ± SD, 1.60 ± 2.14; p = 0.0002). In a model that adjusted for age, sex, household education, smoking, awareness of environmental risk, work type, and animals in house, reported skin conditions were more common in households < 1 km compared with > 2 km from the nearest gas well (odds ratio = 4.1; 95% CI: 1.4, 12.3; p = 0.01). Upper respiratory symptoms were also more frequently reported in persons living in households < 1 km from gas wells (39%) compared with households 1–2 km or > 2 km from the nearest well (31 and 18%, respectively) (p = 0.004). No equivalent correlation was found between well proximity and other reported groups of respiratory, neurological, cardiovascular, or gastrointestinal conditions. Conclusion: Although these results should be viewed as hypothesis generating, and the population studied was limited to households with a ground-fed water supply, proximity of natural gas wells may be associated with the prevalence of health symptoms including dermal and respiratory conditions in residents living near natural gas extraction activities. Further study of these associations, including the role of specific air and water exposures, is warranted. Citation: Rabinowitz PM, Slizovskiy IB, Lamers V, Trufan SJ, Holford TR, Dziura JD, Peduzzi PN, Kane MJ, Reif JS, Weiss TR, Stowe MH. 2015. Proximity to natural gas wells and reported health status: results of a household survey in Washington County, Pennsylvania. Environ Health Perspect 123:21–26; http://dx.doi.org/10.1289/ehp.1307732

Antimicrobial resistance is a growing global health issue. It is also a recognised problem in veterinary medicine. Between September and December 2015 the authors administered a cross-sectional survey to licensed veterinarians in Washington State to assess factors affecting antimicrobial prescribing practices among veterinarians in Washington State. Two hundred and three veterinarians completed the survey. The majority of respondents (166, 82 per cent) were engaged in small animal or exotic animal practice. 24 per cent of respondents reported not ordering culture and sensitivity (C/S) testing in practice. Of the 76 per cent of veterinarians who reported ordering C/S tests, 36 per cent reported ordering such testing ‘often’ or ‘always’ when treating presumptive bacterial infections. Most respondents (65 per cent) mentioned cost as the most common barrier to ordering a C/S test. Only 16 (10 per cent) respondents reported having access to or utilising a clinic-specific antibiogram. This survey demonstrated that while antimicrobials are commonly used in veterinary practice, and veterinarians are concerned about antimicrobial resistance, cost is a barrier to obtaining C/S tests to guide antimicrobial therapy. Summaries of antimicrobial resistance patterns are rarely available to the practising veterinarian. Efforts to promote antimicrobial stewardship in a ‘One Health’ manner should address barriers to the judicious use of antimicrobials in the veterinary practice setting.

INTRODUCTION: Progression from precursor states, MGUS and smoldering multiple myeloma (SMM), to multiple myeloma (MM) is dependent upon adaptive and innate immune contexture shaped by cross-talk between malignant plasma cells and bone marrow (BM) milieu. The complexity and heterogeneity of interactions between the immune system and plasma cells in BM triggers alterations in peripheral blood (PB) immune cell subsets. The advantage of using PB as a surrogate is that dynamic changes in the immune cells can be measured at various time points during disease progression or therapeutic intervention. Here, we performed a comprehensive analysis of immune repertoire to identify immune signatures in PB and BM associated with MM or its precursor states. We also performed T cell receptor (TCR) clonotyping to quantify clonal expansion specific to each immunotype. METHODS: Paired PB and BM specimens were collected from patients with MGUS/SMM (n=12) and MM (n=16) through an IRB-approved biospecimen protocol. PB mononuclear cells and BM mononuclear cells were isolated for immune profiling. A total of 59 immune variables were analyzed by flow cytometry surveying 6 cell lineages' [NK, NK-T, Th, CTL, Treg and ɣδ T cells] distribution and functional status [activation, differentiation and anergy]. In addition, ArcherDx Immunoverse TCR αδ-βɣ CDR3 targeted NGS assay was performed to study clonal distributions of Vα24Jα18 NK-T, βα and ɣδ T cell. Univariate analyses (ANOVA) were performed using p RESULTS: PB immunotyping identified 1 marker of innate inflammation and 9 markers of adaptive T mobilization that differentiated precursor states and MM (p=0.005). This model generated 3 PB immune clusters (Figure): cluster #1 [8 precursor states, 1 MM] showed a lack of innate inflammation and low Th/CTL mobilization, cluster #2 [2MGUS, 5MM] showed low innate inflammation and, cluster #3 [2SMM, 10MM] showed strong innate inflammation (Vɣ9-Vδ2-NKG2D+), Th terminal differentiation (central memory phenotype) and CTL anergy (Tim3+). TCR clonotyping confirmed increased innate inflammation (TCRδ SI 3.99±0.3 vs 4.75±0.15, p BM immunotyping identified 3 markers of innate inflammation and 2 markers of adaptive T mobilization (p=0.0274) distinguishing precursor states from MM. This model generated 3 BM immune clusters: cluster #1 [6 precursor states, 6 MM] showed innate inflammation (ɣδ T) and CTL terminal differentiation (central memory phenotype); cluster #2 [4 SMM, 8 MM] showed innate inflammation (NK-T, ɣδ T) and CTL effector anergy; and cluster #3 [2 MGUS, 2 MM] showed low NK cell cytotoxicity (KIR3DL1+) and CTL terminal differentiation. TCR clonotyping confirmed qualitative differences in innate inflammation between BM cluster #1 and #2 with higher NK-T (%Vα24Jα18 p Comparisons showed associations between PB and BM ɣδ T cell involvement in 13/13 patients. High PB Th/CTL mobilization (terminal differentiation) was associated with high T cell anergy in BM in 9/12 patients; conversely low PB Th/CTL mobilization was associated with low BM T cell involvement in 6/7 patients. CONCLUSION: This pilot study shows immune clustering of MGUS, SMM and MM patients based on BM and PB immunotypes. This is the first study to demonstrate two very distinct MM immunotypes based on low vs. high inflammatory states. We also show a high correlation between innate immune inflammation status in both PB and BM, specifically pertaining to ɣδ T cell, conventional T cell mobilization or lack thereof. Additional studies including a larger cohort for validation and longer follow up to establish correlation with clinical outcomes are currently underway. Figure. Figure. Disclosures Foureau: Teneobio Inc.: Research Funding. Berlin:ArcherDx: Employment. Johnson:ArcherDx: Employment. Williams:ArcherDx: Employment. Voorhees:Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Other: served on an IRC; Amgen Inc.: Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; Oncopeptides: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: served on an IRC; TeneoBio: Consultancy, Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy.

Patients receiving immunosuppressive cancer treatments in settings where there is a high degree of human-animal interaction may be at increased risk for opportunistic zoonotic infections or reactivation of latent infections. We sought to determine the seroprevalence of selected zoonotic pathogens among patients diagnosed with haematologic malignancies and undergoing chemotherapeutic treatments in Romania, where much of the general population lives and/or works in contact with livestock. A convenience sample of 51 patients with haematologic cancer undergoing chemotherapy at a referral clinic in Cluj-Napoca, Romania, was surveyed regarding animal exposures. Blood samples were obtained and tested for evidence of infection with Bartonella species, Coxiella burnetii and Toxoplasma gondii, which are important opportunistic zoonotic agents in immunocompromised individuals. 58.8% of participants reported living or working on a farm, and living or working on a farm was associated with contact with livestock and other animals. 37.5% of participants were IgG seroreactive against one or more of five Bartonella antigens, and seroreactivity was statistically associated with living on farms. Farm dwellers were 3.6 times more likely to test IgG seroreactive to Bartonella antibodies than non-farm dwellers. 47.1% of the participants tested T. gondii IgG positive and 13.7% tested C. burnetii IgG positive, indicating past or latent infection. C. burnetii IgM antibodies were detected in four participants (7.8%), indicating possible recent infection. These results indicate that a large proportion of patients with haematologic cancer in Romania may be at risk for zoonotic infections or for reactivation of latent zoonotic infections, particularly with respect to Bartonella species. Special attention should be paid to cancer patients' exposure to livestock and companion animals in areas where much of the population lives in rural settings.