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AbstractObjective:To evaluate the utility of selective reactive whole-genome sequencing (WGS) in aiding healthcare-associated cluster investigations.Design:Mixed-methods quality-improvement study.Setting:Thes study was conducted across 8 acute-care facilities in an integrated health system.Methods:We analyzed healthcare-associated coronavirus disease 2019 (COVID-19) clusters between May 2020 and July 2022 for which facility infection prevention and control (IPC) teams selectively requested reactive WGS to aid the epidemiologic investigation. WGS was performed with real-time results provided to IPC teams, including genetic relatedness of sequenced isolates. We conducted structured interviews with IPC teams on the informativeness of WGS for transmission investigation and prevention.Results:In total, 8 IPC teams requested WGS to aid the investigation of 17 COVID-19 clusters comprising 226 cases and 116 (51%) sequenced isolates. Of these, 16 (94%) clusters had at least 1 WGS-defined transmission event. IPC teams hypothesized transmission pathways in 14 (82%) of 17 clusters and used data visualizations to characterize these pathways in 11 clusters (65%). The teams reported that in 15 clusters (88%), WGS identified a transmission pathway; the WGS-defined pathway was not one that was predicted by epidemiologic investigation in 7 clusters (41%). WGS changed the understanding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission in 8 clusters (47%) and altered infection prevention interventions in 8 clusters (47%).Conclusions:Selectively utilizing reactive WGS helped identify cryptic SARS-CoV-2 transmission pathways and frequently changed the understanding and response to SARS-CoV-2 outbreaks. Until WGS is widely adopted, a selective reactive WGS approach may be highly impactful in response to healthcare-associated cluster investigations.

AbstractWe estimated the extent of respiratory virus transmission over three pre-COVID-19 seasons. Of 16,273 assays, 22.9% (3,726) detected ≥1 respiratory virus. The frequency of putatively hospital-acquired infection ranged from 6.9% (influenza A/B) to 24.7% (adenovirus). The 176 clusters were most commonly associated with rhinovirus/enterovirus (70) and influenza A/B (62).

AbstractThe National Healthcare Safety Network (NHSN) definitions are critical for standardizing healthcare-associated infection surveillance in US healthcare facilities. However, their use in accurately detecting healthcare-associated transmission (HAT) has not been measured. Using whole-genome sequencing surveillance data, we show that the NHSN has a sensitivity of 44.4% in detecting HAT.

Racial and ethnic minorities are disproportionately affected by end-stage kidney disease (ESKD). ESKD patients on dialysis are at increased risk for Staphylococcus aureusbloodstream infections, but racial, ethnic, and socioeconomic disparities associated with this outcome are not well described.

Objectives Routine surveillance for streptococcal toxic shock syndrome (STSS), a severe manifestation of invasive group A Streptococcus(GAS) infections, likely underestimates its true incidence. The objective of our study was to evaluate routine identification of STSS in a national surveillance system for invasive GAS infections.Methods Active Bacterial Core surveillance (ABCs) conducts active population-based surveillance for invasive GAS disease in selected US counties in 10 states. We categorized invasive GAS cases with a diagnosis of STSS made by a physician as STSS–physician and cases that met the Council of State and Territorial Epidemiologists (CSTE) clinical criteria for STSS based on data in the medical record as STSS–CSTE. We evaluated agreement between the 2 methods for identifying STSS and compared the estimated national incidence of STSS when applying proportions of STSS–CSTE and STSS–physician among invasive GAS cases from this study with national invasive GAS estimates for 2017.Results During 2014-2017, of 7572 invasive GAS cases in ABCs, we identified 1094 (14.4%) as STSS–CSTE and 203 (2.7%) as STSS–physician, a 5.3-fold difference. Of 1094 STSS–CSTE cases, we identified only 132 (12.1%) as STSS–physician cases. Agreement between the 2 methods for identifying STSS was low (κ = 0.17; 95% CI, 0.14-0.19). Using ABCs data, we estimated 591 cases of STSS–physician and 3618 cases of STSS–CSTE occurred nationally in 2017.Conclusions We found a large difference in estimates of incidence of STSS when applying different surveillance methods and definitions. These results should help with better use of currently available surveillance data to estimate the incidence of STSS and to evaluate disease prevention efforts, in addition to guiding future surveillance efforts for STSS.

Through regulation of the epigenome, the bromodomain and extra terminal (BET) family of proteins represent important therapeutic targets for the treatment of human disease. Through mimicking the endogenous N-acetyl-lysine group and disrupting the protein–protein interaction between histone tails and the bromodomain, several small molecule pan-BET inhibitors have progressed to oncology clinical trials. This work describes the medicinal chemistry strategy and execution to deliver an orally bioavailable tetrahydroquinoline (THQ) pan-BET candidate. Critical to the success of this endeavor was a potency agnostic analysis of a data set of 1999 THQ BET inhibitors within the GSK collection which enabled identification of appropriate lipophilicity space to deliver compounds with a higher probability of desired oral candidate quality properties. SAR knowledge was leveraged via Free–Wilson analysis within this design space to identify a small group of targets which ultimately delivered I-BET567 (27), a pan-BET candidate inhibitor that demonstrated efficacy in mouse models of oncology and inflammation.

Historically, anadromous steelhead Oncorhynchus mykissand spring‐run Chinook Salmon O. tshawytschaused high‐elevation rivers in the Sierra Nevada of California but were extirpated in the 20th century by construction of impassable dams. Plans to reintroduce the fish by opening migratory passage across the dams and reservoirs can only succeed if upstream habitats have the capacity to support viable populations of each species. To estimate capacity in the Tuolumne and Merced rivers of the central Sierra Nevada, we used a high‐resolution approach based on remote sensing and dynamic habitat modeling. Our results suggested that for both species in both systems, sediment grain sizes would support widespread spawning and the water temperatures, depths, and velocities would generate ample capacity for fry and juveniles. However, the unregulated Merced River was consistently too warm for adult Chinook Salmon to hold in the dry season prior to spawning, while the regulated Tuolumne River maintained a cooler, more stable thermal regime with a capacity for thousands of holding adults. In our high‐resolution approach, we also discovered several specific physical controls on life history expression, including thermal constraints on the timing of spawning, hydraulic prompts for downstream migration of fry, divergence of the hydraulic niches of steelhead and Chinook Salmon, and a key but uncertain role for thermal tolerance in adult Chinook Salmon. Our results suggested that steelhead reintroduction could succeed in either system and Chinook Salmon could succeed in the Tuolumne River if passage strategies account for large numbers of migrant fry and juveniles driven downstream by winter storms and snowmelt. The Merced River appeared too warm for adult Chinook Salmon, which raises questions about the current limited understanding of thermal tolerance in holding adults. Our study shows how a high‐resolution approach can provide valuable insights on specific limiting factors that must be addressed for reintroduction to succeed.

Introduction: US pneumococcal vaccination recommendations for adults aged 65 years or older recently changed, with options for either 20-valent pneumococcal conjugate vaccine (PCV20) or the combination of 15-valent conjugate vaccine (PCV15) followed by 23-valent polysaccharide vaccine (PPSV23) 1 year later. Underserved minority adults are at higher risk for pneumococcal disease. Methods: A Markov decision analysis model estimated the incremental cost-effectiveness of the newly adopted general population pneumococcal vaccination strategies in older underserved minority adults. The model examined hypothetical 65-year-old US Black cohorts (serving as a proxy for underserved minorities) and non-Black cohorts receiving PCV20 or PCV15/PPSV23, or no vaccination. Main outcome measures included incremental cost-effectiveness per quality-adjusted life year (QALY) gained and pneumococcal disease public health outcomes. Results: Black cohorts had a greater risk of pneumococcal disease hospitalization compared to non-Black cohorts. In Black cohorts, total per person PCV20 strategy costs, compared to no vaccination, were $124 higher while gaining 0.00073 QALY, or $169,540/QALY gained. PCV15/PPSV23 cost $535,797/QALY compared to PCV20. In the non-Black cohort, PCV20 cost $210,529/QALY gained compared to no vaccination and PCV15/PPSV23 cost $728,423/QALY. Plausible variation of vaccine effectiveness minimally affected PCV20 strategy results and made PCV15/PPSV23 more unfavorable. In scenarios where the simpler one-vaccine PCV20 strategy increased absolute vaccine uptake by 10%, PCV20 cost-effectiveness changed minimally while PCV15/PPSV23 cost in excess of $6 million/QALY in the Black cohort. In probabilistic sensitivity analyses that varied all parameters simultaneously, PCV15/PPSV23 was unlikely to be favored at thresholds less than $500,000/QALY gained. Conclusion: General population recommendations for PCV20 use are substantially more economically reasonable in Black and non-Black older adult populations than PCV15/PPSV23. If using a single vaccine increases uptake, which is potentially more likely in the underserved, then PCV20 use becomes even more favorable.

Domain-specific BET bromodomain ligands represent an attractive target for drug discovery with the potential to unlock the therapeutic benefits of antagonizing these proteins without eliciting the toxicological aspects seen with pan-BET inhibitors. While we have reported several distinct classes of BD2 selective compounds, namely, GSK620, GSK549, and GSK046, only GSK046 shows high aqueous solubility. Herein, we describe the lead optimization of a further class of highly soluble compounds based upon a picolinamide chemotype. Focusing on achieving >1000-fold selectivity for BD2 over BD1 ,while retaining favorable physical chemical properties, compound 36was identified as being 2000-fold selective for BD2 over BD1 (Brd4 data) with >1 mg/mL solubility in FaSSIF media. 36represents a valuable new in vivoready molecule for the exploration of the BD2 phenotype.

The profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole 23(GSK809) and furan 24(GSK743) that were derived from the pyrrole fragment 6. We transpose the key learnings from a previous pyridone series (GSK620 2as a representative example) to this novel class of inhibitors, which are characterized by significantly improved solubility relative to our previous research.

The profound efficacy, yet associated toxicity of pan-BET inhibitors is well documented. The possibility of an ameliorated safety profile driven by significantly selective (>100-fold) inhibition of a subset of the eight bromodomains is enticing, but challenging given the close homology. Herein, we describe the X-ray crystal structure-directed optimization of a novel weak fragment ligand with a pan-second bromodomain (BD2) bias, to potent and highly BD2 selective inhibitors. A template hopping approach, enabled by our parallel research into an orthogonal template (15, GSK046), was the basis for the high selectivity observed. This culminated in two tool molecules, 20(GSK620) and 56(GSK549), which showed an anti-inflammatory phenotype in human whole blood, confirming their cellular target engagement. Excellent broad selectivity, developability, and in vivo oral pharmacokinetics characterize these tools, which we hope will be of broad utility to the field of epigenetics research.

Few data on intracranial group A Streptococcus (GAS) infection in children are available. Here, we describe the demographic, clinical, and diagnostic characteristics of 91 children with intracranial GAS infection.

•Whole-genome sequencing can rapidly deliver genetic antimicrobial resistance (AMR) data.•Using genetic AMR data, phenotypic resistance can be predicted.•This predication can be performed using easy-to-use online resistance databases.•High concordance exits between genetic and phenotypic profile amongst MRSA and VRE.

Large‐scale river restoration programs have emerged recently as a tool for improving spawning habitat for native salmonids in highly altered river ecosystems. Few studies have quantified the extent to which restored habitat is utilized by salmonids, which habitat features influence redd site selection, or the persistence of restored habitat over time. We investigated fall‐run Chinook salmon spawning site utilization and measured and modeled corresponding habitat characteristics in two restored reaches: a reach of channel and floodplain enhancement completed in 2013 and a reconfigured channel and floodplain constructed in 2002. Redd surveys demonstrated that both restoration projects supported a high density of salmon redds, 3 and 14 years following restoration. Salmon redds were constructed in coarse gravel substrates located in areas of high sediment mobility, as determined by measurements of gravel friction angles and a grain entrainment model. Salmon redds were located near transitions between pool‐riffle bedforms in regions of high predicted hyporheic flows. Habitat quality (quantified as a function of stream hydraulics) and hyporheic flow were both strong predictors of redd occurrence, though the relative roles of these variables differed between sites. Our findings indicate that physical controls on redd site selection in restored channels were similar to those reported for natural channels elsewhere. Our results further highlight that in addition to traditional habitat criteria (e.g., water depth, velocity, and substrate size), quantifying sediment texture and mobility, as well as intragravel flow, provides a more complete understanding of the ecological benefits provided by river restoration projects. River channel morphology, habitat quality, and streambed hyporheic fluxes provided important cues for salmon redd site selectionNew tools combined with field measurements allow for analysis of the full suite of hypothesized controls on redd site selectionExtended field studies and analysis of restoration projects identify critical factors and processes that are commonly not included in concept development and restoration design

Racial disparities in U.S. adult pneumococcal vaccination rates persist despite reduced barriers to access. Consequently, racial and ethnic minorities experience pneumococcal disease at higher rates than whites. This study examined prevalence of high-risk conditions and pneumococcal hospitalizations among U.S. black and non-black populations aged ≥50 years.

ABSTRACTIn the U.S., pneumococcal polysaccharide vaccine (PPSV23) uptake among high-risk adults aged <65 years is consistently low and improvement is needed. One barrier to improved vaccine coverage is the complexity of the adult vaccination schedule. This exploratory analysis compared the cost-effectiveness of strategies to increase pneumococcal vaccine uptake in high-risk adults aged 50–64 years. We used a Markov model to compare strategies for non-immunocompromised 50–64 year olds: 1) current pneumococcal polysaccharide vaccine (PPSV23) recommendations; 2) current recommendations enhanced by an intervention; 3) PPSV23 plus pneumococcal conjugate vaccine (PCV13) for high-risk patients with no intervention; or 4) both vaccines for all 50-year-olds with no intervention. Parameters included CDC data and other US data, varied extensively in sensitivity analyses. In the analysis, vaccinating high-risk individuals with PPSV23/PCV13 was the least costly strategy, with total costs of $424/person. Vaccinating all 50 year olds with PPSV23/PCV13 cost $40 more and gained 0.00068 quality-adjusted life years (QALY), or $57,786/QALY gained. Current recommendations with or without an intervention program were more expensive and less effective than other strategies. In multi-way sensitivity analyses, the current recommendations/intervention program strategy was favored at a $100,000/QALY threshold only if non-bacteremic pneumococcal pneumonia rate or PCV13 serotype coverage were substantially lower than base case values. Thus, an intervention program to improve pneumococcal vaccine uptake among high-risk 50–64 year-olds was not cost-effective in most scenarios. High-risk individuals receiving both PCV13 and PPSV23 could be economically favorable, and vaccinating all 50-year-olds with both vaccines could be considered.

IMPORTANCE: Group B Streptococcus (GBS) is an important cause of invasive bacterial disease. Previous studies have shown a substantial and increasing burden of GBS infections among nonpregnant adults, particularly older adults and those with underlying medical conditions. OBJECTIVE: To update trends of invasive GBS disease among US adults using population-based surveillance data. DESIGN, SETTING, AND PARTICIPANTS: In this population-based surveillance study, a case was defined as isolation of GBS from a sterile site between January 1, 2008, and December 31, 2016. Demographic and clinical data were abstracted from medical records. Rates were calculated using US Census data. Antimicrobial susceptibility testing and serotyping were performed on a subset of isolates. Case patients were residents of 1 of 10 catchment areas of the Active Bacterial Core surveillance (ABCs) network, representing approximately 11.5% of the US adult population. Patients were included in the study if they were nonpregnant, were 18 years or older, were residents of an ABCs catchment site, and had a positive GBS culture from a normally sterile body site. MAIN OUTCOMES AND MEASURES: Trends in GBS cases overall and by demographic characteristics (sex, age, and race), underlying clinical conditions of patients, and isolate characteristics are described. RESULTS: The ABCs network detected 21 250 patients with invasive GBS among nonpregnant adults from 2008 through 2016. The GBS incidence in this population increased from 8.1 cases per 100 000 population in 2008 to 10.9 in 2016 (P = .002 for trend). There were 3146 cases reported in 2016 (59% male; median age, 64 years; age range, 18-103 years). The GBS incidence was higher among men than women and among blacks than whites and increased with age. Projected to the US population, an estimated 27 729 cases of invasive disease and 1541 deaths occurred in the United States in 2016. Ninety-five percent of cases in 2016 occurred in someone with at least 1 underlying condition, most commonly obesity (53.9%) and diabetes (53.4%). Resistance to clindamycin increased from 37.0% of isolates in 2011 to 43.2% in 2016 (P = .02). Serotypes Ia, Ib, II, III, and V accounted for 86.4% of isolates in 2016; serotype IV increased from 4.7% in 2008 to 11.3% in 2016 (P &lt; .001 for trend). CONCLUSIONS AND RELEVANCE: The public health burden of invasive GBS disease among nonpregnant adults is substantial and continues to increase. Chronic diseases, such as obesity and diabetes, may contribute.

AbstractBackground:Identifying routes of transmission among hospitalized patients during a healthcare-associated outbreak can be tedious, particularly among patients with complex hospital stays and multiple exposures. Data mining of the electronic health record (EHR) has the potential to rapidly identify common exposures among patients suspected of being part of an outbreak.Methods:We retrospectively analyzed 9 hospital outbreaks that occurred during 2011–2016 and that had previously been characterized both according to transmission route and by molecular characterization of the bacterial isolates. We determined (1) the ability of data mining of the EHR to identify the correct route of transmission, (2) how early the correct route was identified during the timeline of the outbreak, and (3) how many cases in the outbreaks could have been prevented had the system been running in real time.Results:Correct routes were identified for all outbreaks at the second patient, except for one outbreak involving >1 transmission route that was detected at the eighth patient. Up to 40 or 34 infections (78% or 66% of possible preventable infections, respectively) could have been prevented if data mining had been implemented in real time, assuming the initiation of an effective intervention within 7 or 14 days of identification of the transmission route, respectively.Conclusions:Data mining of the EHR was accurate for identifying routes of transmission among patients who were part of the outbreak. Prospective validation of this approach using routine whole-genome sequencing and data mining of the EHR for both outbreak detection and route attribution is ongoing.

IMPORTANCE: Invasive disease owing to group B Streptococcus (GBS) remains an important cause of illness and death among infants younger than 90 days in the United States, despite declines in early-onset disease (EOD; with onset at 0-6 days of life) that are attributed to intrapartum antibiotic prophylaxis (IAP). Maternal vaccines to prevent infant GBS disease are currently under development. OBJECTIVE: To describe incidence rates, case characteristics, antimicrobial resistance, and serotype distribution of EOD and late-onset disease (LOD; with onset at 7-89 days of life) in the United States from 2006 to 2015 to inform IAP guidelines and vaccine development. DESIGN, SETTING, AND PARTICIPANTS: This study used active population-based and laboratory-based surveillance for invasive GBS disease conducted through Active Bacterial Core surveillance in selected counties of 10 states across the United States. Residents of Active Bacterial Core surveillance areas who were younger than 90 days and had invasive GBS disease in 2006 to 2015 were included. Data were analyzed from December 2017 to April 2018. EXPOSURES: Group B Streptococcus isolated from a normally sterile site. MAIN OUTCOMES AND MEASURES: Early-onset disease and LOD incidence rates and associated GBS serotypes and antimicrobial resistance. RESULTS: The Active Bacterial Core surveillance program identified 1277 cases of EOD and 1387 cases of LOD. From 2006 to 2015, EOD incidence declined significantly from 0.37 to 0.23 per 1000 live births (P &lt; .001), and LOD rates remained stable (mean, 0.31 per 1000 live births). Among the mothers of 1277 infants with EOD, 617 (48.3%) had no indications for IAP and did not receive it, and 278 (21.8%) failed to receive IAP despite having indications. Serotype data were available for 1743 of 1897 patients (91.3%) from 7 sites that collect GBS isolates. Among patients with EOD, serotypes Ia (242 [27.3%]) and III (242 [27.3%]) were most common. Among patients with LOD, serotype III was most common (481 [56.2%]), and this increased from 2006 to 2015 from 0.12 to 0.20 cases per 1000 live births (P &lt; .001). Serotype IV caused 53 cases (6.2%) of EOD and LOD combined. The 6 most common serotypes (Ia, Ib, II, III, IV, and V) caused 881 EOD cases (99.3%) and 853 LOD cases (99.7%). No β-lactam resistance was identified; 359 isolates (20.8%) tested showed constitutive clindamycin resistance. In 2015, an estimated 840 EOD cases and 1265 LOD cases occurred nationally. CONCLUSIONS AND RELEVANCE: The rates of LOD among US infants are now higher than EOD rates. Combined with addressing IAP implementation gaps, an effective vaccine covering the most common serotypes might further reduce EOD rates and help prevent LOD, for which there is no current public health intervention.

Remote sensing has become an increasingly viable tool for characterizing fluvial systems. In this study, we used field measurements with a 1.6‐km reach of the upper Sacramento River, CA, to evaluate the potential of mapping water depths with a range of platforms, sensors, and depth retrieval methods. Field measurements of water column optical properties also were compared to similar data sets from other rivers to provide context for our results. We considered field spectra, a multispectral satellite image, hyperspectral data collected from conventional and unmanned aircraft, and a bathymetric LiDAR and applied a generalized version of Optimal Band Ratio Analysis and the Knearest neighbors regression machine learning algorithm. Linear, quadratic, exponential, power, and lowess Optimal Band Ratio Analysis models enabled flexible curve‐fitting in calibrating spectrally based quantities to depth; an exponential formulation avoided artifacts associated with other model types. Knearest neighbors regression increased observed versus predicted (OP) R2values, particularly for the satellite image; we also found that preprocessing of satellite images was unnecessary and that a basic data product could be used for depth retrieval. Bathymetric LiDAR was highly accurate and precise in shallow water, but a lack of bottom returns from areas greater than 2 m deep resulted in large gaps in coverage. The maximum detectable depth imposes an important constraint on fluvial remote sensing and a hybrid approach combined with field surveys of deep areas might be a more realistic operational strategy for bathymetric mapping. Future work will focus on scaling up from short reaches to long river segments. Accurate depths were retrieved from satellite images, hyperspectral data acquired from manned and unmanned aircraft, and a bathymetric LiDARGeneralized Optimal Band Ratio Analysis allows flexible calibration of spectral quantities to depth; exponential model avoids artifactsThe maximum detectable depth is a key constraint on fluvial remote sensing, particularly for LiDAR due to a lack of bottom returns >2 m

AbstractObjectiveRecovery of multidrug-resistant (MDR) Pseudomonas aeruginosaand Klebsiella pneumoniaefrom a cluster of patients in the medical intensive care unit (MICU) prompted an epidemiologic investigation for a common exposure.MethodsClinical and microbiologic data from MICU patients were retrospectively reviewed, MICU bronchoscopes underwent culturing and borescopy, and bronchoscope reprocessing procedures were reviewed. Bronchoscope and clinical MDR isolates epidemiologically linked to the cluster underwent molecular typing using pulsed-field gel electrophoresis (PFGE) followed by whole-genome sequencing.ResultsOf the 33 case patients, 23 (70%) were exposed to a common bronchoscope (B1). Both MDR P. aeruginosaand K. pneumoniawere recovered from the bronchoscope’s lumen, and borescopy revealed a luminal defect. Molecular testing demonstrated genetic relatedness among case patient and B1 isolates, providing strong evidence for horizontal bacterial transmission. MDR organism (MDRO) recovery in 19 patients was ultimately linked to B1 exposure, and 10 of 19 patients were classified as belonging to an MDRO pseudo-outbreak.ConclusionsSurveillance of bronchoscope-derived clinical culture data was important for early detection of this outbreak, and whole-genome sequencing was important for the confirmation of findings. Visualization of bronchoscope lumens to confirm integrity should be a critical component of device reprocessing.

Candida is a leading cause of healthcare-associated bloodstream infections in the United States. Infants and children have unique risk factors for candidemia, and the Candida species distribution in this group is different that among adults; however, candidemia epidemiology in this population has not been described recently.

ABSTRACTAfrica historically has had the highest incidence of meningococcal disease with high endemic rates and periodic epidemics. The meningitis belt, a region of sub-Saharan Africa extending from Senegal to Ethiopia, has experienced large, devastating epidemics. However, dramatic shifts in the epidemiology of meningococcal disease have occurred recently. For instance, meningococcal capsular group A (NmA) epidemics in the meningitis belt have essentially been eliminated by use of conjugate vaccine. However, NmW epidemics have emerged and spread across the continent since 2000; NmX epidemics have occurred sporadically, and NmC recently emerged in Nigeria and Niger. Outside the meningitis belt, NmB predominates in North Africa, while NmW followed by NmB predominate in South Africa. Improved surveillance is necessary to address the challenges of this changing epidemiologic picture. A low-cost, multivalent conjugate vaccine covering NmA and the emergent and prevalent meningococcal capsular groups C, W, and X in the meningitis belt is a pressing need.

HIV‐infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long‐term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI.

HIV-infected individuals (HIVI) are threatened by meningococcal infection and presented lower response to vaccines. Data are scarce on long-term persistence of human serum bactericidal antibody (hSBA) after a meningococcal C conjugate (MCC) vaccine in HIVI youth; the authors aimed to describe this persistence in HIVI.

Bacille Calmette-Guérin (BCG) vaccination is known to cause false-positive tuberculin skin test (TST) results from cross-reactions with mycobacterial antigens. However, the duration of BCG vaccination influence on the TST is poorly characterized. The objective of this study was to assess the long-term effect of BCG vaccination on TST reactivity.

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the US for prevention of invasive pneumococcal disease in children. Individual-level socioeconomic status (SES) is a potential confounder of the estimated effectiveness of PCV13 and is often controlled for in observational studies using zip code as a proxy. We assessed the utility of zip code matching for control of SES in a post-licensure evaluation of the effectiveness of PCV13 (calculated as [1-matched odds ratio]*100). We used a directed acyclic graph to identify subsets of confounders and collected SES variables from birth certificates, geocoding, a parent interview, and follow-up with medical providers. Cases tended to be more affluent than eligible controls (for example, 48.3% of cases had private insurance vs. 44.6% of eligible controls), but less affluent than enrolled controls (52.9% of whom had private insurance). Control of confounding subsets, however, did not result in a meaningful change in estimated vaccine effectiveness (original estimate: 85.1%, 95% CI 74.8–91.9%; adjusted estimate: 82.5%, 95% CI 65.6–91.1%). In the context of a post-licensure vaccine effectiveness study, zip code appears to be an adequate, though not perfect, proxy for individual SES.

Multi‐dimensional numerical models are fundamental tools for investigating biophysical processes in aquatic ecosystems. Remote sensing techniques increase the feasibility of applying such models at riverscape scales, but tests of model performance on large rivers have been limited. We evaluated the potential to develop two‐dimensional (2D) and three‐dimensional (3D) hydrodynamic models for a 1.6‐km reach of a large gravel‐bed river using three sources of remotely sensed river bathymetry. We estimated depth from hyperspectral image data acquired from conventional and uncrewed aircraft and multispectral satellite imagery. Our results indicated that modeled water depth errors were similar between 2D and 3D models, with depth residuals that were comparable to the uncertainty associated with the bathymetry used as input. We found good agreement between measured and modeled depth‐averaged velocities generated by 2D and 3D models, while 3D models provided superior predictions of near‐bed velocities. We found that optimal model performance occurred for lower flow resistance values than previously reported in the literature, possibly as a consequence of the high‐resolution bathymetry used as model input. Model predictions of winter‐run Chinook salmon (Oncorhynchus tshawytscha) spawning and rearing habitat were not sensitive to the source of bathymetric information, but bioenergetic predictions related to adult holding costs were influenced by the input bathymetry. Our results suggest that hyperspectral imagery acquired from piloted and/or uncrewed aircraft can be used to map the bathymetry of clear‐flowing, relatively shallow large rivers with sufficient accuracy to support multi‐dimensional flow model development; models developed from multispectral satellite imagery had more limited predictive capability. This study demonstrated the potential to support multi‐dimensional flow model development on a large river using remotely sensed bathymetryHyperspectral imagery acquired via piloted/uncrewed aircraft was more suitable than multispectral imagery for parameterizing flow modelsModeled salmon habitat metrics were less sensitive than bioenergetic predictions of fish movement to source bathymetry This study demonstrated the potential to support multi‐dimensional flow model development on a large river using remotely sensed bathymetry Hyperspectral imagery acquired via piloted/uncrewed aircraft was more suitable than multispectral imagery for parameterizing flow models Modeled salmon habitat metrics were less sensitive than bioenergetic predictions of fish movement to source bathymetry

In 2010, 13-valent pneumococcal conjugate vaccine (PCV13) was licensed and recommended in the USA for prevention of invasive pneumococcal disease in children. Licensure was based on immunogenicity data comparing PCV13 with the earlier seven-valent formulation. Because clinical endpoints were not assessed for the new antigens, we did a postlicensure matched case-control study to assess vaccine effectiveness.

Escherichia coliO157:H7 is a common cause of foodborne illness in the United States. Beef ground at establishments regulated by the U.S. Department of Agriculture, Food Safety and Inspection Service is routinely tested for E. coliO157:H7. Prior to December 2013, boxed beef product (wholesale cuts of beef, such as beef loin, packaged into bags and boxed for shipping) was not always tested for this pathogen. Downstream processors or retailers may grind the product; and, if the ground beef is not cooked to the recommended temperature, pathogens on the exterior of the beef introduced to the interior through grinding may survive. On 18 October 2013, the Allegheny County Health Department identified two E. coliO157:H7 cases, both of whom were food handlers at restaurant A, a restaurant that ground locally produced boxed beef for hamburgers on site. Case finding was conducted through public messaging, employee surveys, and disease surveillance. All potential cases were interviewed using a standard questionnaire. A confirmed case was defined as laboratory-confirmed E. coliO157:H7 with exposure to restaurant A. A probable case was defined as a patient with compatible symptoms and exposure to restaurant A but without laboratory confirmation. All human and food isolates were characterized by pulsed-field gel electrophoresis and multilocus variable-number tandem repeat analysis. The analysis identified 14 confirmed and 10 probable cases of E. coli; 18 nonintact ground beef samples tested positive for E. coliO157:H7. Nine confirmed cases were restaurant A employees. All confirmed cases recalled eating a restaurant A hamburger in the 10 days before illness onset; most cases reported consuming medium to rare hamburgers. Multiple pulsed-field gel electrophoresis and multilocus variable-number tandem repeat analysis patterns were identified among both the human and ground beef isolates, and the patient isolates matched those found in ground beef samples. Restaurant A voluntarily closed for 1.5 days, changed beef suppliers, ceased grinding beef in-house, and has had no new cases since reopening.

We aimed to evaluate the Meningococcal (Neisseria meningitidis) C conjugated (MCC) vaccine seroconversion and adverse events (AEs) in HIV-infected and HIV-uninfected children and adolescents in Rio de Janeiro, Brazil.

AbstractSteelhead Oncorhynchus mykiss(anadromous Rainbow Trout) near the southern limit of the species’ range commonly use shallow alluvial rivers for migration, spawning, and rearing. These rivers have been widely modified for water management, and an enduring question is whether their rehabilitation would create summer nursery habitat for steelhead. We used process-based models to evaluate the thermal potential for steelhead nursery habitat in the Santa Ynez River, California, a regulated alluvial river that currently supports few steelhead. We assessed (1) how well a calibrated model of river heat fluxes predicted summer temperature patterns for a warm year and an average year; (2) whether those patterns created thermal potential for the rapid growth that is characteristic of steelhead nursery habitat; and (3) whether manipulation of flows from an upstream dam significantly altered thermal potential. In the heat flux model, the root mean square error for 15-min temperatures was 1.51°C, about three times greater than that of the larger, deeper Sacramento River in northern California. Generally, the Santa Ynez River was thermally suitable but stressful for juvenile steelhead. Flow augmentation reduced the number of thermally stressful days only near the dam, but it reduced the intensity of thermal stress throughout the river. Daytime movement of steelhead into natural, thermally stratified pools would reduce stress intensity by similar levels. In this region, O. mykisscommonly pursue an anadromous (steelhead) life history by entering nursery habitat early in their first or second summer and rapidly growing to attain a threshold size for anadromy by fall. In the average year, the river was thermally suitable for the first-summer pathway under high food availability and for the second-summer pathway under medium food availability. The warm year also supported the second-summer pathway under high food availability. Currently, the Santa Ynez River's capacity to support these pathways does not appear to be limited by summer temperature, thus indicating a need to identify other limiting factors.Received July 21, 2014; accepted November 5, 2014