Update: COVID-19 Among Workers in Meat and Poultry Processing Facilities - United States, April-May 2020.

Meat and poultry processing facilities face distinctive challenges in the control of infectious diseases, including coronavirus disease 2019 (COVID-19) (1). COVID-19 outbreaks among meat and poultry processing facility workers can rapidly affect large numbers of persons. Assessment of COVID-19 cases among workers in 115 meat and poultry processing facilities through April 27, 2020, documented 4,913 cases and 20 deaths reported by 19 states (1). This report provides updated aggregate data from states regarding the number of meat and poultry processing facilities affected by COVID-19, the number and demographic characteristics of affected workers, and the number of COVID-19-associated deaths among workers, as well as descriptions of interventions and prevention efforts at these facilities. Aggregate data on confirmed COVID-19 cases and deaths among workers identified and reported through May 31, 2020, were obtained from 239 affected facilities (those with a laboratory-confirmed COVID-19 case in one or more workers) in 23 states.* COVID-19 was confirmed in 16,233 workers, including 86 COVID-19-related deaths. Among 14 states reporting the total number of workers in affected meat and poultry processing facilities (112,616), COVID-19 was diagnosed in 9.1% of workers. Among 9,919 (61%) cases in 21 states with reported race/ethnicity, 87% occurred among racial and ethnic minority workers. Commonly reported interventions and prevention efforts at facilities included implementing worker temperature or symptom screening and COVID-19 education, mandating face coverings, adding hand hygiene stations, and adding physical barriers between workers. Targeted workplace interventions and prevention efforts that are appropriately tailored to the groups most affected by COVID-19 are critical to reducing both COVID-19-associated occupational risk and health disparities among vulnerable populations. Implementation of these interventions and prevention efforts† across meat and poultry processing facilities nationally could help protect workers in this critical infrastructure industry.

Bacillus Calmette-Guérin Cases Reported to the National Tuberculosis Surveillance System, United States, 2004-2015.

Mycobacterium bovis bacillus Calmette-Guérin (BCG) is used as a vaccine to protect against disseminated tuberculosis (TB) and as a treatment for bladder cancer. We describe characteristics of US TB patients reported to the National Tuberculosis Surveillance System (NTSS) whose disease was attributed to BCG. We identified 118 BCG cases and 91,065 TB cases reported to NTSS during 2004-2015. Most patients with BCG were US-born (86%), older (median age 75 years), and non-Hispanic white (81%). Only 17% of BCG cases had pulmonary involvement, in contrast with 84% of TB cases. Epidemiologic features of BCG cases differed from TB cases. Clinicians can use clinical history to discern probable BCG cases from TB cases, enabling optimal clinical management. Public health agencies can use this information to quickly identify probable BCG cases to avoid inappropriately reporting BCG cases to NTSS or expending resources on unnecessary public health interventions.

Response to Isoniazid-Resistant Tuberculosis in Homeless Shelters, Georgia, USA, 2015-2017.

In 2008, an outbreak of isoniazid-resistant tuberculosis was identified among residents of homeless shelters in Atlanta, Georgia, USA. When initial control efforts involving standard targeted testing failed, a comprehensive approach that involved all providers of services for the homeless successfully interrupted the outbreak.

Changes in Tuberculosis Disparities at a Time of Decreasing Tuberculosis Incidence in the United States, 1994-2016.

OBJECTIVES: To assess national progress in reducing disparities in rates of tuberculosis (TB) disease, which disproportionately affects minorities. METHODS: We used Centers for Disease Control and Prevention (CDC) surveillance data and US Census data to calculate TB rates for 1994 through 2016 by race/ethnicity, national origin, and other TB risk factors. We assessed progress in reducing disparities with rate ratios (RRs) and indexes of disparity, defined as the average of the differences between subpopulation and all-population TB rates divided by the all-population rate. RESULTS: Although TB rates decreased for all subpopulations, RRs increased or stayed the same for all minorities compared with Whites. For racial/ethnic groups, indexes of disparity decreased from 1998 to 2008 (P < .001) but increased thereafter (P = .33). The index of disparity by national origin increased an average of 1.5% per year. CONCLUSIONS: Although TB rates have decreased, disparities have persisted and even increased for some populations. To address the problem, the CDC's Division of TB Elimination has focused on screening and treating latent TB infection, which is concentrated among minorities and is the precursor for more than 85% of TB cases in the United States.

Outbreak of Drug-Resistant Mycobacterium tuberculosis Among Homeless People in Atlanta, Georgia, 2008-2015.

OBJECTIVES: Our objective was to describe and determine the factors contributing to a recent drug-resistant tuberculosis (TB) outbreak in Georgia. METHODS: We defined an outbreak case as TB diagnosed from March 2008 through December 2015 in a person residing in Georgia at the time of diagnosis and for whom (1) the genotype of the Mycobacterium tuberculosis isolate was consistent with the outbreak strain or (2) TB was diagnosed clinically without a genotyped isolate available and connections were established to another outbreak-associated patient. To determine factors contributing to transmission, we interviewed patients and reviewed health records, homeless facility overnight rosters, and local jail booking records. We also assessed infection control measures in the 6 homeless facilities involved in the outbreak. RESULTS: Of 110 outbreak cases in Georgia, 86 (78%) were culture confirmed and isoniazid resistant, 41 (37%) occurred in people with human immunodeficiency virus coinfection (8 of whom were receiving antiretroviral treatment at the time of TB diagnosis), and 10 (9%) resulted in TB-related deaths. All but 8 outbreak-associated patients had stayed overnight or volunteered extensively in a homeless facility; all these facilities lacked infection control measures. At least 9 and up to 36 TB cases outside Georgia could be linked to this outbreak. CONCLUSIONS: This article highlights the ongoing potential for long-lasting and far-reaching TB outbreaks, particularly among populations with untreated human immunodeficiency virus infection, mental illness, substance abuse, and homelessness. To prevent and control TB outbreaks, health departments should work with overnight homeless facilities to implement infection control measures and maintain searchable overnight rosters.

Design and synthesis of affinity chromatography ligands for the purification of 5-hydroxyeicosanoid dehydrogenase.

Arachidonic acid (AA) is converted to biologically active metabolites by different pathways, one of the most important of which is initiated by 5-lipoxygenase (5-LO). 5-Hydroxyeicosatetraenoic acid (5-HETE), although possessing only weak biological activity itself, is oxidized to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent chemoattractant for eosinophils and neutrophils. Our main goal is to determine how the biosynthesis of 5-oxo-ETE is regulated and to determine its pathophysiological roles. To achieve this task, we designed and synthesized affinity chromatography ligands for the purification of 5-hydroxyeicosanoid dehydrogenase (5-HEDH), the enzyme responsible for the formation of 5-oxo-ETE.

Tuberculosis - United States, 1993-2010.

Tuberculosis (TB) is transmitted via the airborne route by person-to-person contact. Although TB is a leading cause of death on a global scale, most cases can be cured with treatment. From 1993 to 2010, the number of TB cases reported in the United States decreased from 25,103 to 11,182. Despite the decrease, TB continues to affect many communities in the United States disproportionately and unequally, especially racial/ethnic minorities and foreign-born persons. TB remains one of many diseases and health conditions with large disparities and inequalities by income, race/ethnicity, educational attainment, and other sociodemographic characteristics.

Effects of Hylan G-F 20 supplementation on cartilage preservation detected by magnetic resonance imaging in osteoarthritis of the knee: a two-year single-blind clinical trial.

BACKGROUND: Although viscosupplementation is an effective symptomatic treatment for knee osteoarthritis (OA), the effect of longer term administration on articular cartilage has not been fully explored. We examined the effect of viscosupplementation with Hylan G-F 20 on knee cartilage over 2 years in patients with knee OA. METHODS: In this prospective, single-blind, parallel control group pilot study, 78 patients with symptomatic knee OA (Kellgren-Lawrence grade II and III) were assigned to either intervention group (n = 39 receiving 4 courses of 3 × 2.0 ml of intra-articular Hylan G-F 20 injections at 6 month intervals) or control group (n = 39 receiving usual care for knee OA without injections). Magnetic resonance imaging of the study knee was performed at baseline, 12 and 24 months. Cartilage volume and defects were assessed using validated methods. RESULTS: Fifty-five subjects (71%) completed 24 month follow up. Over 24 months, the intervention group had a reduced annual percentage rate of medial and lateral tibial cartilage volume loss (mean ± SD, -0.3 ± 2.7% and -1.4 ± 4.3%) compared with the control group (2.3 ± 2.6% and 1.4 ± 2.6%, P = 0.001 and 0.005 for difference, respectively). The intervention group also showed reduced cartilage defect score increment in the medial tibiofemoral compartment (0.1 ± 1.3) compared with the control group (0.8 ± 1.5, P = 0.05). CONCLUSIONS: Six monthly intra-articular injections of Hylan G-F 20 administered to patients with symptomatic knee OA have a beneficial effect on knee cartilage preservation measured by both cartilage volume and cartilage defects. Hylan G-F 20 warrants further evaluation in larger clinical trials as a possible disease-modifying agent in the treatment of knee OA. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov (NCT00393393).

Enhanced formation of 5-oxo-6,8,11,14-eicosatetraenoic acid by cancer cells in response to oxidative stress, docosahexaenoic acid and neutrophil-derived 5-hydroxy-6,8,11,14-eicosatetraenoic acid.

The 5-lipoxygenase (5-LO) product 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), which is a potent chemoattractant for myeloid cells, is known to promote the survival of prostate cancer cells. In the present study, we found that PC3 prostate cancer cells and cell lines derived from breast (MCF7) and lung (A-427) cancers contain 5-hydroxyeicosanoid dehydrogenase (5-HEDH) activity and have the ability to synthesize 5-oxo-ETE from its precursor 5S-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) when added as an exogenous substrate. H(2)O(2) strongly stimulated the synthesis of 5-oxo-ETE and induced dramatic increases in the levels of both glutathione disulfide and NADP(+). The effects of H(2)O(2) on 5-oxo-ETE and NADP(+) were blocked by N-ethylmaleimide (NEM), indicating that this effect was mediated by the glutathione reductase-dependent generation of NADP(+), the cofactor required by 5-HEDH. 5-Oxo-ETE synthesis was also stimulated by agents that have cytotoxic effects on tumor cells, including 4,7,10,13,16,19-docosahexaenoic acid, tamoxifen and MK-886. Because PC3 cells have only modest 5-LO activity compared with inflammatory cells, we investigated their ability to contribute to the transcellular biosynthesis of 5-oxo-ETE from neutrophil-derived 5-HETE. Stimulation of neutrophils with arachidonic acid and calcium ionophore in the presence of PC3 cells led to a large and selective increase in 5-oxo-ETE synthesis compared with controls in which PC3 cell 5-oxo-ETE synthesis was selectively blocked by pretreatment with NEM. The ability of prostate tumor cells to synthesize 5-oxo-ETE may contribute to tumor cell proliferation as well as the influx of inflammatory cells, which may further induce cell proliferation through the release of cytokines. 5-Oxo-ETE may be an attractive target in cancer therapy.

5-oxo-ETE is a major oxidative stress-induced arachidonate metabolite in B lymphocytes.

B lymphocytes convert arachidonic acid (AA) to the 5-lipoxygenase products leukotriene B4 (LTB4) and 5-hydroxy-6,8,11,14-eicosatetraenoic acid (5-HETE) when subjected to oxidative stress. 5-HETE has little biological activity, but can be oxidized by a selective dehydrogenase in some cells to 5-oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE), a potent eosinophil chemoattractant. We found that CESS cells, a B lymphocyte cell line, convert AA to 5-oxo-ETE and this is selectively stimulated by oxidative stress. In the presence of H2O2, 5-oxo-ETE is a major AA metabolite in these cells (5-oxo-ETE≈5-HETE>LTB4). The cyclooxygenase product 12-hydroxy-5,8,10-heptadecatrienoic acid is also formed, but is not affected by H2O2. Diamide had effects similar to those of H2O2 and both substances had similar effects on human tonsillar B cells. H2O2 also stimulated 5-oxo-ETE formation from its direct precursor 5-HETE in tonsillar B and CESS cells, and this was inhibited by the glutathione reductase inhibitor carmustine. H2O2 concomitantly induced rapid increases in GSSG and NADP+ and reductions in GSH and NADPH. We conclude that oxidative stress stimulates 5-oxo-ETE synthesis in B lymphocytes by two mechanisms: activation of 5-lipoxygenase and increased oxidation of 5-HETE by NADP+-dependent 5-hydroxyeicosanoid dehydrogenase. B lymphocyte-derived 5-oxo-ETE could contribute to eosinophilic inflammation in asthma and other allergic diseases.

5-Oxo-ETE and the OXE receptor.

5-Oxo-ETE is a product of the 5-lipoxygenase pathway that is formed by the oxidation of 5-HETE by 5-hydroxyeicosanoid dehydrogenase (5-HEDH). 5-HEDH is a microsomal NADP(+)-dependent enzyme that is highly selective for 5-HETE. 5-Oxo-ETE synthesis is regulated by intracellular NADP(+) levels and is dramatically increased under conditions that favor oxidation of NADPH to NADP(+) such as oxidative stress and the respiratory burst in phagocytic cells. 5-Oxo-ETE is a potent chemoattractant for eosinophils and has similar effects on neutrophils, basophils and monocytes. It elicits infiltration of eosinophils and, to a lesser extent, neutrophils into the skin after intradermal injection in humans. It also promotes the survival of tumor cells and has been shown to block the induction of apoptosis by 5-LO inhibitors. 5-Oxo-ETE acts by the G(i/o)-coupled OXE receptor, which was also known as TG1019, R527 and hGPCR48. Although the pathophysiological role of 5-oxo-ETE is not well understood, it may play important roles in asthma and allergic diseases, cancer, and cardiovascular disease. The availability of a selective antagonist would help to clarify the role of 5-oxo-ETE and may be of therapeutic benefit.

Substrate selectivity of 5-hydroxyeicosanoid dehydrogenase and its inhibition by 5-hydroxy-Delta6-long-chain fatty acids.

5-Oxo-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-oxo-ETE) is a metabolite of the 5-lipoxygenase (5-LO) product 5S-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid (5-HETE), formed by the microsomal enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). 5-oxo-ETE is a chemoattractant for neutrophils and eosinophils, both in vitro and in vivo. To examine the substrate selectivity of 5-HEDH and to search for potential inhibitors, we prepared a series of 5S-hydroxy fatty acids (C(12) to C(20) containing zero to four double bonds) by total chemical synthesis and examined their metabolism by microsomes from monocytic U937 cells. Although most of these fatty acids were oxidized to their 5-oxo metabolites by 5-HEDH, 5-HETE seemed to be the best substrate. However, substrates containing less than 16 carbons, a methylated alpha-carboxyl group, or a hydroxyl group at the omega-end of the molecule were not substantially metabolized. Some of the fatty acids tested were fairly potent inhibitors of the formation of 5-oxo-ETE by 5-HEDH, in particular 5-hydroxy-6-octadecenoic acid and 5-hydroxy-6-eicosenoic acid. Both substances selectively inhibited 5-oxo-ETE formation by human peripheral blood mononuclear cells incubated with arachidonic acid and calcium ionophore without affecting the formation of leukotriene B(4), 12-HETE, or 12-hydroxy-5,8,10-heptadecatrienoic acid. We conclude that the requirements for appreciable metabolism by 5-HEDH include a chain length of at least 16 carbons, a free alpha-carboxyl group, and a hydrophobic group at the omega-end of the molecule. 5-Hydroxy-Delta(6) C(18) and C(20) fatty acids selectively inhibit 5-HEDH without inhibiting 5-LO, leukotriene A(4) hydrolase, 12-lipoxygenase, or cyclooxygenase. Such compounds may be useful in defining the role of 5-oxo-ETE and its mechanism of synthesis.

Enantio- and stereospecific syntheses of 15(R)-Me-PGD2, a potent and selective DP2-receptor agonist.

The first total synthesis of 15(R)-Me-PGD2 3 is reported. The synthesis is based on the enantioselective and stereospecific syntheses of synthon 17 and its attachment to the five-membered ring by a olefin cross metathesis reaction. This approach permits the introduction of a side chain with a predetermined stereogenic center into the prostanoid ring, resulting in the synthesis of 15R-methyl prostaglandin D2 and allows rapid access to other prostanoids.

Regulation of 5-hydroxyeicosanoid dehydrogenase activity in monocytic cells.

The 5-lipoxygenase product 5-oxo-ETE (5-oxo-eicosatetraenoic acid) is a highly potent granulocyte chemoattractant that is synthesized from 5-HETE (5-hydroxyeicosatetraenoic acid) by 5-HEDH (5-hydroxyeicosanoid dehydrogenase). In the present study, we found that 5-HEDH activity is induced in U937 monocytic cells by differentiation towards macrophages with PMA and in HL-60 myeloblastic cells by 1,25-dihydroxy-vitamin D3. We used PMA-differentiated U937 cells to investigate further the regulation of 5-HEDH. This enzyme exhibits approx. 10000-fold selectivity for NADP+ over NAD+ as a cofactor for the oxidation of 5-HETE, which is maximal at pH 10.2. In contrast, the reverse reaction (5-oxo-ETE-->5-HETE) is NADPH-dependent and is maximal at pH 6. Although the K(m) for the forward reaction (670 nM) is about twice that for the reverse reaction at neutral pH, the V(max) is approx 8-fold higher. The oxidation of 5-HETE to 5-oxo-ETE is supported by very low concentrations of NADP(+) (K(m) 139 nM), inhibited by NADPH (K(i) 224 nM) and is consistent with a ping-pong mechanism. The amount of 5-oxo-ETE synthesized by 5-HEDH depends on the ratio of NADP+ to NADPH. Exposure of U937 cells to oxidative stress (t-butyl hydroperoxide) increased the ratio of NADP+ to NADPH from approx. 0.08 in resting cells to approx. 3, and this was accompanied by a dramatic increase in 5-HETE oxidation to 5-oxo-ETE. We conclude that differentiation of monocytic cells towards macrophages results in enhanced 5-oxo-ETE synthesis and that the ability of cells to synthesize 5-oxo-ETE is tightly regulated by the ratio of intracellular NADP+ to NADPH.

A SPME-GC procedure for monitoring peppermint flavor in tablets.

A method was developed using solid-phase microextraction (SPME) and gas chromatography to monitor the peppermint flavor loss in a taste-masked tablet formulation. This was accomplished by headspace sampling of two major components of peppermint: menthone and menthol. It was found that the excipients from the tablet produced an important matrix effect and that standard addition analysis was necessary for improved accuracy of the determination. The method was shown to be specific and precise. Furthermore, the method produced acceptable results with adequate quantitation limits to determine peppermint flavors in taste-masked tablets. The optimized extraction procedure was successfully used to monitor the stability of peppermint flavor in an oral solid formulation. The accelerated stability studies of the tablet showed that the menthone and menthol was lost in an exponential manner and levels off after several days of heat exposure.