Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-29 (of 29 Records) |
Query Trace: Theodore S [original query] |
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Mild traumatic brain injuries and risk for affective and behavioral disorders
Delmonico RL , Tucker LY , Theodore BR , Camicia M , Filanosky C , Haarbauer-Krupa J . Pediatrics 2024 153 (2) OBJECTIVES: Recent studies document an association between mild traumatic brain injuries (mTBIs) in children and postinjury psychiatric disorders. However. these studies were subject to limitations in the design, lack of long-term follow-up, and poorly defined psychiatric outcomes. This study determines the incidence and relative risk of postinjury new affective and behavior disorders 4 years after mTBIs. METHODS: A cohort study of mTBI cases and matched comparisons within an integrated health care system. The mTBI group included patients ≤17 years of age, diagnosed with mTBI from 2000 to 2014 (N = 18 917). Comparisons included 2 unexposed patients (N = 37 834) per each mTBI-exposed patient, randomly selected and matched for age, sex, race/ethnicity, and date of medical visit (reference date to mTBI injury). Outcomes included a diagnosis of affective or behavioral disorders in the 4 years after mTBI or the reference date. RESULTS: Adjusted risks for affective disorders were significantly higher across the first 3 years after injury for the mTBI group, especially during the second year, with a 34% increase in risk. Adjusted risks for behavioral disorders were significant at years 2 and 4, with up to a 37% increase in risk. The age group with the highest risk for postinjury affective and behavioral disorders was 10- to 13-year-old patients. CONCLUSIONS: Sustaining an mTBI significantly increased the risks of having a new affective or behavioral disorder up to 4 years after injury. Initial and ongoing screening for affective and behavior disorders following an mTBI can identify persistent conditions that may pose barriers to recovery. |
Lessons learned for public health workforce development: An evaluation of the Centers For Disease Control And Prevention's Laboratory Leadership Service Fellowship
McColloch C , Davis M , Araujo A , Theodore S , Barkley J , Paek M , Henning T . Eval Program Plann 2022 95 102147 The Centers for Disease Control and Prevention launched the Laboratory Leadership Service (LLS) Fellowship Program in July 2015 to develop public health laboratory (PHL) leaders who will improve PHL quality and safety. This article describes a retrospective, summative evaluation to determine the extent to which LLS has met its short-term goals for PHL workforce development. The evaluation relied on existing data from routine LLS data collection and reporting, supplemented with a new alumni survey. The purpose of the design was threefold: 1) to reduce data collection burden on program staff and participants, 2) to assess the value and limits of routine fellowship data for comprehensive public health workforce development program evaluation, and 3) to identify ways to improve LLS's routine data collections for program evaluation. We used descriptive statistics, qualitative analysis, and participatory methods (i.e., a data party) to analyze and interpret data. Results show LLS short-term outcome achievement and highlight opportunities for program improvement, particularly related to the design of certain training requirements and for future evaluations. Overall, the evaluation contributes to lessons learned for PHL workforce development efforts, including how routine data collections can contribute to comprehensive public health workforce development evaluations. |
COVID-19 Infections among Students and Staff in New York City Public Schools.
Varma JK , Thamkittikasem J , Whittemore K , Alexander M , Stephens DH , Arslanian K , Bray J , Long TG . Pediatrics 2021 147 (5) BACKGROUND: The 2019 novel coronavirus disease (COVID-19) pandemic led many jurisdictions to close in-person school instruction. METHODS: We collected data about COVID-19 cases associated with New York City (NYC) public schools from polymerase chain reaction testing performed in each school on a sample of asymptomatic students and staff and from routine reporting. We compared prevalence from testing done in schools to community prevalence estimates from statistical models. We compared cumulative incidence for school-associated cases to all cases reported to the city. School-based contacts were monitored to estimate the secondary attack rate and possible direction of transmission. RESULTS: To assess prevalence, we analyzed data from 234 132 persons tested for severe acute respiratory syndrome coronavirus 2 infection in 1594 NYC public schools during October 9 to December 18, 2020; 986 (0.4%) tested positive. COVID-19 prevalence in schools was similar to or less than estimates of prevalence in the community for all weeks. To assess cumulative incidence, we analyzed data for 2231 COVID-19 cases that occurred in students and staff compared with the 86 576 persons in NYC diagnosed with COVID-19 during the same period; the overall incidence was lower for persons in public schools compared with the general community. Of 36 423 school-based close contacts, 191 (0.5%) subsequently tested positive for COVID-19; the likely index case was an adult for 78.0% of secondary cases. CONCLUSIONS: We found that in-person learning in NYC public schools was not associated with increased prevalence or incidence overall of COVID-19 infection compared with the general community. |
Comprehensive Analysis of the Glycan Complement of SARS-CoV-2 Spike Proteins Using Signature Ions-Triggered Electron-Transfer/Higher-Energy Collisional Dissociation (EThcD) Mass Spectrometry.
Wang D , Baudys J , Bundy JL , Solano M , Keppel T , Barr JR . Anal Chem 2020 92 (21) 14730-14739 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to a global pandemic of coronavirus disease 2019 (COVID-19). The spike protein expressed on the surface of this virus is highly glycosylated and plays an essential role during the process of infection. We conducted a comprehensive mass spectrometric analysis of the N-glycosylation profiles of the SARS-CoV-2 spike proteins using signature ions-triggered electron-transfer/higher-energy collision dissociation (EThcD) mass spectrometry. The patterns of N-glycosylation within the recombinant ectodomain and S1 subunit of the SARS-CoV-2 spike protein were characterized using this approach. Significant variations were observed in the distribution of glycan types as well as the specific individual glycans on the modification sites of the ectodomain and subunit proteins. The relative abundance of sialylated glycans in the S1 subunit compared to the full-length protein could indicate differences in the global structure and function of these two species. In addition, we compared N-glycan profiles of the recombinant spike proteins produced from different expression systems, including human embryonic kidney (HEK 293) cells and Spodoptera frugiperda (SF9) insect cells. These results provide useful information for the study of the interactions of SARS-CoV-2 viral proteins and for the development of effective vaccines and therapeutics. |
SARS-CoV-2 Infections and Serologic Responses from a Sample of U.S. Navy Service Members - USS Theodore Roosevelt, April 2020.
Payne DC , Smith-Jeffcoat SE , Nowak G , Chukwuma U , Geibe JR , Hawkins RJ , Johnson JA , Thornburg NJ , Schiffer J , Weiner Z , Bankamp B , Bowen MD , MacNeil A , Patel MR , Deussing E , CDC COVID-19 Surge Laboratory Group , Tiller Rebekah , Galloway Rene , Rogers Shannon , Whitaker Brett , Kondas Ashley , Smith Peyton , Lee Christopher , Graziano James , Gillingham BL . MMWR Morb Mortal Wkly Rep 2020 69 (23) 714-721 Compared with the volume of data on coronavirus disease 2019 (COVID-19) outbreaks among older adults, relatively few data are available concerning COVID-19 in younger, healthy persons in the United States (1,2). In late March 2020, the aircraft carrier USS Theodore Roosevelt arrived at port in Guam after numerous U.S. service members onboard developed COVID-19. In April, the U.S. Navy and CDC investigated this outbreak, and the demographic, epidemiologic, and laboratory findings among a convenience sample of 382 service members serving aboard the aircraft carrier are reported in this study. The outbreak was characterized by widespread transmission with relatively mild symptoms and asymptomatic infection among this sample of mostly young, healthy adults with close, congregate exposures. Service members who reported taking preventive measures had a lower infection rate than did those who did not report taking these measures (e.g., wearing a face covering, 55.8% versus 80.8%; avoiding common areas, 53.8% versus 67.5%; and observing social distancing, 54.7% versus 70.0%, respectively). The presence of neutralizing antibodies, which represent antibodies that inhibit SARS-CoV-2, among the majority (59.2%) of those with antibody responses is a promising indicator of at least short-term immunity. This report improves the understanding of COVID-19 in the U.S. military and among young adults in congregate settings and reinforces the importance of preventive measures to lower risk for infection in similar environments. |
Cost-Effectiveness of Risk-Stratified Colorectal Cancer Screening Based on Polygenic Risk: Current Status and Future Potential.
Naber SK , Kundu S , Kuntz KM , Dotson WD , Williams MS , Zauber AG , Calonge N , Zallen DT , Ganiats TG , Webber EM , Goddard KAB , Henrikson NB , van Ballegooijen M , Janssens Acjw , Lansdorp-Vogelaar I . JNCI Cancer Spectr 2020 4 (1) pkz086 BACKGROUND: Although uniform colonoscopy screening reduces colorectal cancer (CRC) mortality, risk-based screening may be more efficient. We investigated whether CRC screening based on polygenic risk is a cost-effective alternative to current uniform screening, and if not, under what conditions it would be. METHODS: The MISCAN-Colon model was used to simulate a hypothetical cohort of US 40-year-olds. Uniform screening was modeled as colonoscopy screening at ages 50, 60, and 70 years. For risk-stratified screening, individuals underwent polygenic testing with current and potential future discriminatory performance (area under the receiver-operating curve [AUC] of 0.60 and 0.65-0.80, respectively). Polygenic testing results were used to create risk groups, for which colonoscopy screening was optimized by varying the start age (40-60 years), end age (70-85 years), and interval (1-20 years). RESULTS: With current discriminatory performance, optimal screening ranged from once-only colonoscopy at age 60 years for the lowest-risk group to six colonoscopies at ages 40-80 years for the highest-risk group. While maintaining the same health benefits, risk-stratified screening increased costs by $59 per person. Risk-stratified screening could become cost-effective if the AUC value would increase beyond 0.65, the price per polygenic test would drop to less than $141, or risk-stratified screening would lead to a 5% increase in screening participation. CONCLUSIONS: Currently, CRC screening based on polygenic risk is unlikely to be cost-effective compared with uniform screening. This is expected to change with a greater than 0.05 increase in AUC value, a greater than 30% reduction in polygenic testing costs, or a greater than 5% increase in adherence with screening. |
Mutations in TAC1B : a Novel Genetic Determinant of Clinical Fluconazole Resistance in Candida auris.
Rybak JM , Munoz JF , Barker KS , Parker JE , Esquivel BD , Berkow EL , Lockhart SR , Gade L , Palmer GE , White TC , Kelly SL , Cuomo CA , Rogers PD . mBio 2020 11 (3) Candida auris has emerged as a multidrug-resistant pathogen of great clinical concern. Approximately 90% of clinical C. auris isolates are resistant to fluconazole, the most commonly prescribed antifungal agent, and yet it remains unknown what mechanisms underpin this fluconazole resistance. To identify novel mechanisms contributing to fluconazole resistance in C. auris, fluconazole-susceptible C. auris clinical isolate AR0387 was passaged in media supplemented with fluconazole to generate derivative strains which had acquired increased fluconazole resistance in vitro Comparative analyses of comprehensive sterol profiles, [(3)H]fluconazole uptake, sequencing of C. auris genes homologous to genes known to contribute to fluconazole resistance in other species of Candida, and relative expression levels of C. auris ERG11, CDR1, and MDR1 were performed. All fluconazole-evolved derivative strains were found to have acquired mutations in the zinc-cluster transcription factor-encoding gene TAC1B and to show a corresponding increase in CDR1 expression relative to the parental clinical isolate, AR0387. Mutations in TAC1B were also identified in a set of 304 globally distributed C. auris clinical isolates representing each of the four major clades. Introduction of the most common mutation found among fluconazole-resistant clinical isolates of C. auris into fluconazole-susceptible isolate AR0387 was confirmed to increase fluconazole resistance by 8-fold, and the correction of the same mutation in a fluconazole-resistant isolate, AR0390, decreased fluconazole MIC by 16-fold. Taken together, these data demonstrate that C. auris can rapidly acquire resistance to fluconazole in vitro and that mutations in TAC1B significantly contribute to clinical fluconazole resistance.IMPORTANCE Candida auris is an emerging multidrug-resistant pathogen of global concern, known to be responsible for outbreaks on six continents and to be commonly resistant to antifungals. While the vast majority of clinical C. auris isolates are highly resistant to fluconazole, an essential part of the available antifungal arsenal, very little is known about the mechanisms contributing to resistance. In this work, we show that mutations in the transcription factor TAC1B significantly contribute to clinical fluconazole resistance. These studies demonstrated that mutations in TAC1B can arise rapidly in vitro upon exposure to fluconazole and that a multitude of resistance-associated TAC1B mutations are present among the majority of fluconazole-resistant C. auris isolates from a global collection and appear specific to a subset of lineages or clades. Thus, identification of this novel genetic determinant of resistance significantly adds to the understanding of clinical antifungal resistance in C. auris. |
Streptococcus pyogenes pbp2x Mutation Confers Reduced Susceptibility to β-lactam antibiotics.
Vannice K , Ricaldi J , Nanduri S , Fang FC , Lynch J , Bryson-Cahn C , Wright T , Duchin J , Kay M , Chochua S , Van Beneden C , Beall B . Clin Infect Dis 2019 71 (1) 201-204 Two near-identical clinical Streptococcus pyogenes isolates of emm subtype emm43.4 with a pbp2x missense mutation (T553K) were detected. Minimum inhibitory concentrations (MICs) for ampicillin and amoxicillin were 8-fold higher, and the MIC for cefotaxime was 3-fold higher than for near-isogenic control isolates, consistent with a first-step in developing beta-lactam resistance. |
Development and Implementation of Multiplex TaqMan Array Cards for Specimen Testing at Child Health and Mortality Prevention Surveillance Site Laboratories.
Diaz MH , Waller JL , Theodore MJ , Patel N , Wolff BJ , Benitez AJ , Morris T , Raghunathan PL , Breiman RF , Whitney CG , Blau DM , Winchell JM . Clin Infect Dis 2019 69 S311-s321 Child Health and Mortality Prevention Surveillance (CHAMPS) laboratories are employing a variety of laboratory methods to identify infectious agents contributing to deaths of children <5 years old and stillbirths in sub-Saharan Africa and South Asia. In support of this long-term objective, our team developed TaqMan Array Cards (TACs) for testing postmortem specimens (blood, cerebrospinal fluid, lung tissue, respiratory tract swabs, and rectal swabs) for >100 real-time polymerase chain reaction (PCR) targets in total (30-45 per card depending on configuration). Multipathogen panels were configured by syndrome and customized to include pathogens of significance in young children within the regions where CHAMPS is conducted, including bacteria (57 targets covering 30 genera), viruses (48 targets covering 40 viruses), parasites (8 targets covering 8 organisms), and fungi (3 targets covering 3 organisms). The development and application of multiplex real-time PCR reactions to the TAC microfluidic platform increased the number of targets in each panel while maintaining assay efficiency and replicates for heightened sensitivity. These advances represent a substantial improvement in the utility of this technology for infectious disease diagnostics and surveillance. We optimized all aspects of the CHAMPS molecular laboratory testing workflow including nucleic acid extraction, quality assurance, and data management to ensure comprehensive molecular testing of specimens and high-quality data. Here we describe the development and implementation of multiplex TACs and associated laboratory protocols for specimen processing, testing, and data management at CHAMPS site laboratories. |
New filovirus disease classification and nomenclature.
Kuhn JH , Adachi T , Adhikari NKJ , Arribas JR , Bah IE , Bausch DG , Bhadelia N , Borchert M , Brantsaeter AB , Brett-Major DM , Burgess TH , Chertow DS , Chute CG , Cieslak TJ , Colebunders R , Crozier I , Davey RT , de Clerck H , Delgado R , Evans L , Fallah M , Fischer WA 2nd , Fletcher TE , Fowler RA , Grunewald T , Hall A , Hewlett A , Hoepelman AIM , Houlihan CF , Ippolito G , Jacob ST , Jacobs M , Jakob R , Jacquerioz FA , Kaiser L , Kalil AC , Kamara RF , Kapetshi J , Klenk HD , Kobinger G , Kortepeter MG , Kraft CS , Kratz T , Bosa HSK , Lado M , Lamontagne F , Lane HC , Lobel L , Lutwama J , Lyon GM 3rd , Massaquoi MBF , Massaquoi TA , Mehta AK , Makuma VM , Murthy S , Musoke TS , Muyembe-Tamfum JJ , Nakyeyune P , Nanclares C , Nanyunja M , Nsio-Mbeta J , O'Dempsey T , Paweska JT , Peters CJ , Piot P , Rapp C , Renaud B , Ribner B , Sabeti PC , Schieffelin JS , Slenczka W , Soka MJ , Sprecher A , Strong J , Swanepoel R , Uyeki TM , van Herp M , Vetter P , Wohl DA , Wolf T , Wolz A , Wurie AH , Yoti Z . Nat Rev Microbiol 2019 17 (5) 261-263 The recent large outbreak of Ebola virus disease (EVD) in Western Africa resulted in greatly increased accumulation of human genotypic, phenotypic and clinical data, and improved our understanding of the spectrum of clinical manifestations. As a result, the WHO disease classification of EVD underwent major revision. |
Prevalence of Amyotrophic Lateral Sclerosis - United States, 2015.
Mehta P , Kaye W , Raymond J , Punjani R , Larson T , Cohen J , Muravov O , Horton K . MMWR Morb Mortal Wkly Rep 2018 67 (46) 1285-1289 Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged >/=60 years, and those with a family history of ALS are more likely to develop the disease (2). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Treatments currently available, Edaravone and Riluzole, do not cure ALS, but slow disease progression in certain patients (3,4). This report presents National ALS Registry findings regarding ALS prevalence in the United States for the period January 1-December 31, 2015. In 2015, the estimated prevalence of ALS cases was 5.2 per 100,000 population with a total of 16,583 cases identified. Overall, these findings are similar to the 2014 ALS prevalence and case count (5.0 per 100,000; 15,927 cases) (2). Prevalence rates by patient characteristics (most common in whites, males, and persons aged >/=60 years) and U.S. Census regions are consistent with ALS demographics and have not changed from 2014 to 2015 calendar years. The algorithm used to identify cases from national administrative databases was updated from the International Classification of Diseases, Ninth Revision (ICD-9) to the ICD-10 codes for claims starting on October 1, 2015, with no apparent effect on case ascertainment. Data collected by the National ALS Registry are being used to better describe the epidemiology of ALS in the United States and to facilitate research on the genetics, potential biomarkers, environmental pollutants, and etiology for ALS. |
Is seizure frequency variance a predictable quantity
Goldenholz DM , Goldenholz SR , Moss R , French J , Lowenstein D , Kuzniecky R , Haut S , Cristofaro S , Detyniecki K , Hixson J , Karoly P , Cook M , Strashny A , Theodore WH . Ann Clin Transl Neurol 2018 5 (2) 201-207 Background: There is currently no formal method for predicting the range expected in an individual's seizure counts. Having access to such a prediction would be of benefit for developing more efficient clinical trials, but also for improving clinical care in the outpatient setting. Methods: Using three independently collected patient diary datasets, we explored the predictability of seizure frequency. Three independent seizure diary databases were explored: SeizureTracker (n = 3016), Human Epilepsy Project (n = 93), and NeuroVista (n = 15). First, the relationship between mean and standard deviation in seizure frequency was assessed. Using that relationship, a prediction for the range of possible seizure frequencies was compared with a traditional prediction scheme commonly used in clinical trials. A validation dataset was obtained from a separate data export of SeizureTracker to further verify the predictions. Results: A consistent mathematical relationship was observed across datasets. The logarithm of the average seizure count was linearly related to the logarithm of the standard deviation with a high correlation (R(2) > 0.83). The three datasets showed high predictive accuracy for this log-log relationship of 94%, compared with a predictive accuracy of 77% for a traditional prediction scheme. The independent validation set showed that the log-log predicted 94% of the correct ranges while the RR50 predicted 77%. Conclusion: Reliably predicting seizure frequency variability is straightforward based on knowledge of mean seizure frequency, across several datasets. With further study, this may help to increase the power of RCTs, and guide clinical practice. |
Prevalence of Amyotrophic Lateral Sclerosis - United States, 2014.
Mehta P , Kaye W , Raymond J , Wu R , Larson T , Punjani R , Heller D , Cohen J , Peters T , Muravov O , Horton K . MMWR Morb Mortal Wkly Rep 2018 67 (7) 216-218 Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a progressive and fatal neuromuscular disease; the majority of ALS patients die within 2-5 years of receiving a diagnosis (1). Familial ALS, a hereditary form of the disease, accounts for 5%-10% of cases, whereas the remaining sporadic cases have no clearly defined etiology (1). ALS affects persons of all races and ethnicities; however, whites, males, non-Hispanics, persons aged >60 years, and those with a family history of ALS are more likely to develop the disease (1-3). No cure for ALS has yet been identified, and the lack of proven and effective therapeutic interventions is an ongoing challenge. Current treatments available do not cure ALS but have been shown to slow disease progression. Until recently, only one drug (riluzole) was approved to treat ALS; however, in 2017, the Food and Drug Administration approved a second drug, edaravone (4). |
A multi-dataset time-reversal approach to clinical trial placebo response and the relationship to natural variability in epilepsy
Goldenholz DM , Strashny A , Cook M , Moss R , Theodore WH . Seizure 2017 53 31-36 PURPOSE: Clinical epilepsy drug trials have been measuring increasingly high placebo response rates, up to 40%. This study was designed to examine the relationship between the natural variability in epilepsy, and the placebo response seen in trials. We tested the hypothesis that 'reversing' trial direction, with the baseline period as the treatment observation phase, would reveal effects of natural variability. METHOD: Clinical trial simulations were run with time running forward and in reverse. Data sources were: SeizureTracker.com (patient reported diaries), a randomized sham-controlled TMS trial, and chronically implanted intracranial EEG electrodes. Outcomes were 50%-responder rates (RR50) and median percentage change (MPC). RESULTS: The RR50 results showed evidence that temporal reversal does not prevent large responder rates across datasets. The MPC results negative in the TMS dataset, and positive in the other two. CONCLUSIONS: Typical RR50s of clinical trials can be reproduced using the natural variability of epilepsy as a substrate across multiple datasets. Therefore, the placebo response in epilepsy clinical trials may be attributable almost entirely to this variability, rather than the "placebo effect". |
Does accounting for seizure frequency variability increase clinical trial power?
Goldenholz DM , Goldenholz SR , Moss R , French J , Lowenstein D , Kuzniecky R , Haut S , Cristofaro S , Detyniecki K , Hixson J , Karoly P , Cook M , Strashny A , Theodore WH , Pieper C . Epilepsy Res 2017 137 145-151 OBJECTIVE: Seizure frequency variability is associated with placebo responses in randomized controlled trials (RCT). Increased variability can result in drug misclassification and, hence, decreased statistical power. We investigated a new method that directly incorporated variability into RCT analysis, ZV. METHODS: Two models were assessed: the traditional 50%-responder rate (RR50), and the variability-corrected score, ZV. Each predicted seizure frequency upper and lower limits using prior seizures. Accuracy was defined as percentage of time-intervals when the observed seizure frequencies were within the predicted limits. First, we tested the ZV method on three datasets (SeizureTracker: n=3016, Human Epilepsy Project: n=107, and NeuroVista: n=15). An additional independent SeizureTracker validation dataset was used to generate a set of 200 simulated trials each for 5 different sample sizes (total N=100 to 500 by 100), assuming 20% dropout and 30% drug efficacy. "Power" was determined as the percentage of trials successfully distinguishing placebo from drug (p<0.05). RESULTS: Prediction accuracy across datasets was, ZV: 91-100%, RR50: 42-80%. Simulated RCT ZV analysis achieved >90% power at N=100 per arm while RR50 required N=200 per arm. SIGNIFICANCE: ZV may increase the statistical power of an RCT relative to the traditional RR50. |
Executive Summary: 2016 Infectious Diseases Society of America (IDSA) clinical practice guideline for the treatment of coccidioidomycosis
Galgiani JN , Ampel NM , Blair JE , Catanzaro A , Geertsma F , Hoover SE , Johnson RH , Kusne S , Lisse J , MacDonald JD , Meyerson SL , Raksin PB , Siever J , Stevens DA , Sunenshine R , Theodore N . Clin Infect Dis 2016 63 (6) 717-22 It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure. |
2016 Infectious Diseases Society of America (IDSA) Clinical Practice Guideline for the Treatment of Coccidioidomycosis
Galgiani JN , Ampel NM , Blair JE , Catanzaro A , Geertsma F , Hoover SE , Johnson RH , Kusne S , Lisse J , MacDonald JD , Meyerson SL , Raksin PB , Siever J , Stevens DA , Sunenshine R , Theodore N . Clin Infect Dis 2016 63 (6) e112-46 It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. Infectious Diseases Society of America considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.Coccidioidomycosis, also known as San Joaquin Valley fever, is a systemic infection endemic to parts of the southwestern United States and elsewhere in the Western Hemisphere. Residence in and recent travel to these areas are critical elements for the accurate recognition of patients who develop this infection. In this practice guideline, we have organized our recommendations to address actionable questions concerning the entire spectrum of clinical syndromes. These can range from initial pulmonary infection, which eventually resolves whether or not antifungal therapy is administered, to a variety of pulmonary and extrapulmonary complications. Additional recommendations address management of coccidioidomycosis occurring for special at-risk populations. Finally, preemptive management strategies are outlined in certain at-risk populations and after unintentional laboratory exposure. |
Identification and Characterization of Microsatellite Markers Derived from the Whole Genome Analysis of Taenia solium.
Pajuelo MJ , Eguiluz M , Dahlstrom E , Requena D , Guzman F , Ramirez M , Sheen P , Frace M , Sammons S , Cama V , Anzick S , Bruno D , Mahanty S , Wilkins P , Nash T , Gonzalez A , Garcia HH , Gilman RH , Porcella S , Zimic M . PLoS Negl Trop Dis 2015 9 (12) e0004316 BACKGROUND: Infections with Taenia solium are the most common cause of adult acquired seizures worldwide, and are the leading cause of epilepsy in developing countries. A better understanding of the genetic diversity of T. solium will improve parasite diagnostics and transmission pathways in endemic areas thereby facilitating the design of future control measures and interventions. Microsatellite markers are useful genome features, which enable strain typing and identification in complex pathogen genomes. Here we describe microsatellite identification and characterization in T. solium, providing information that will assist in global efforts to control this important pathogen. METHODS: For genome sequencing, T. solium cysts and proglottids were collected from Huancayo and Puno in Peru, respectively. Using next generation sequencing (NGS) and de novo assembly, we assembled two draft genomes and one hybrid genome. Microsatellite sequences were identified and 36 of them were selected for further analysis. Twenty T. solium isolates were collected from Tumbes in the northern region, and twenty from Puno in the southern region of Peru. The size-polymorphism of the selected microsatellites was determined with multi-capillary electrophoresis. We analyzed the association between microsatellite polymorphism and the geographic origin of the samples. RESULTS: The predicted size of the hybrid (proglottid genome combined with cyst genome) T. solium genome was 111 MB with a GC content of 42.54%. A total of 7,979 contigs (>1,000 nt) were obtained. We identified 9,129 microsatellites in the Puno-proglottid genome and 9,936 in the Huancayo-cyst genome, with 5 or more repeats, ranging from mono- to hexa-nucleotide. Seven microsatellites were polymorphic and 29 were monomorphic within the analyzed isolates. T. solium tapeworms were classified into two genetic groups that correlated with the North/South geographic origin of the parasites. CONCLUSIONS/SIGNIFICANCE: The availability of draft genomes for T. solium represents a significant step towards the understanding the biology of the parasite. We report here a set of T. solium polymorphic microsatellite markers that appear promising for genetic epidemiology studies. |
Absence of high molecular weight proteins 1 and/or 2 is associated with decreased adherence among non-typeable Haemophilus influenzae clinical isolates
Vuong J , Wang X , Theodore JM , Whitmon J , Gomez de Leon P , Mayer LW , Carlone GM , Romero-Steiner S . J Med Microbiol 2013 62 1649-56 High molecular weight (Hmw) proteins 1 and 2, type IV pilin protein (PilA), outer-membrane protein P5 (OmpP5), Haemophilus protein D (Hpd) and Haemophilus adhesive protein (Hap) are surface proteins involved in the adherence of non-typeable Haemophilus influenzae. One hundred clinical isolates were evaluated for the presence of the genes encoding these proteins by PCR and for their adherence capacity (AC) to Detroit 562 nasopharyngeal cells (D562). The majority of isolates were from blood (77/100); other sites were also represented. Confluent D562 monolayers (1.2x10(5) cells per well) were inoculated with standardized minimal infective doses (m.o.i.) of 10(2), 10(3) or 10(4) c.f.u. per well. The AC was categorized as low (<10 %) or high (≥10 %) depending on the percentage of c.f.u. adhering per well. All the isolates evaluated showed adherence: 69/100 (69 %) demonstrated high adherence, while 31/100 (31 %) showed low adherence. Of all the genes evaluated, hmw1A and/or hmw2A were detected in 69/100 (69 %) of isolates. The presence of hmw1A and/or hmw2A was associated with increased adherence to D562 cells (P≤0.001). Dot immunoblots were performed to detect protein expression using mAbs 3D6, AD6 and 10C5. Among the high-adherence isolates (n = 69), 72 % reacted with 3D6 and 21 % with 10C5. Our data indicate that the absence of Hmw1 and/or Hmw2 was associated with decreased adherence to D562 cells. |
Low rates of hepatitis screening and vaccination of HIV-infected MSM in HIV clinics
Hoover KW , Butler M , Workowski KA , Follansbee S , Gratzer B , Hare CB , Johnston B , Theodore JL , Tao G , Smith BD , Chorba T , Kent CK . Sex Transm Dis 2012 39 (5) 349-353 BACKGROUND: HIV-infected men who have sex with men (MSM) are at increased risk of viral hepatitis because of similar behavioral risk factors for acquisition of these infections. Our objective was to estimate adherence to HIV management guidelines that recommend screening HIV-infected persons for hepatitis A, B, and C infection, and vaccinating for hepatitis A and B if susceptible. METHODS: We evaluated hepatitis prevention services received by a random sample of HIV-infected MSM in 8 HIV clinics in 6 US cities. We abstracted medical records of all visits made by the patients to the clinic during the period from 2004 to 2007, to estimate hepatitis screening and vaccination rates overall and by clinic site. RESULTS: Medical records of 1329 patients who had 14,831 visits from 2004 to 2006 were abstracted. Screening rates for hepatitis A, B, and C were 47%, 52%, and 54%, respectively. Among patients who were screened and found to be susceptible, 29% were vaccinated for hepatitis A and 25% for hepatitis B. The percentage of patients screened and vaccinated varied significantly by clinic. CONCLUSIONS: Awareness of hepatitis susceptibility and hepatitis coinfection status in HIV-infected patients is essential for optimal clinical management. Despite recommendations for hepatitis screening and vaccination of HIV-infected MSM, rates were suboptimal at all clinic sites. These low rates highlight the importance of routine review of adherence to recommended clinical services. Such reviews can prompt the development and implementation of simple and sustainable interventions to improve the quality of care. |
Evaluation of new biomarker genes for differentiating Haemophilus influenzae from Haemophilus haemolyticus.
Theodore MJ , Anderson RD , Wang X , Katz LS , Vuong JT , Bell ME , Juni BA , Lowther SA , Lynfield R , Macneil JR , Mayer LW . J Clin Microbiol 2012 50 (4) 1422-4 PCR detecting the protein D (hpd) and fuculose kinase (fucK) genes showed high sensitivity and specificity for identifying Haemophilus influenzae and differentiating it from H. haemolyticus. Phylogenetic analysis using the 16S rRNA gene demonstrated two distinct groups for H. influenzae and H. haemolyticus. |
Clinical validation of multiplex real-time PCR assays for detection of bacterial meningitis pathogens.
Wang X , Theodore MJ , Mair R , Trujillo-Lopez E , du Plessis M , Wolter N , Baughman AL , Hatcher C , Vuong J , Lott L , von Gottberg A , Sacchi C , McDonald JM , Messonnier NE , Mayer LW . J Clin Microbiol 2011 50 (3) 702-8 Neisseria meningitidis (Nm), Haemophilus influenzae (Hi), and Streptococcus pneumoniae (Sp) are important causes of meningitis and other infections, and rapid, sensitive, and specific laboratory assays are critical for effective public health interventions. Singleplex real-time PCR assays have been developed to detect Nm ctrA, Hi hpd and Sp lytA, and serogroup-specific genes in the cap locus for Nm serogroups A, B, C, W135, X and Y. However, the assay sensitivity for serogroups B, W135 and Y is low. We aimed to improve assay sensitivity and develop multiplex assays to reduce time and cost. New singleplex real-time PCR assays B-synD, W-synG, and Y-synF showed 100% specificity for detecting Nm species, with high sensitivity [B-synD, 99%(75/76); W-synG, 97%(38/39); and Y-synF, 100%(66/66)]. The lower limit of detection (LLD) was 9, 43 and 10 copies/reaction for B-synD, W-synG, and Y-synF assays, respectively, a significant improvement compared to the previous singleplex assays. We developed three multiplex real-time PCR assays for detection of: (i) Nm ctrA, Hi hpd and Sp lytA (NHS); (ii) Nm serogroups A, W135 and X (AWX), and (iii) Nm serogroups B, C and Y (BCY). Each multiplex assay was 100% specific for detecting its target organisms or serogroups, and the LLD was similar to that for singleplex. Pairwise comparison of real-time PCR between multiplex and singleplex showed that cycle threshold values of the multiplex were similar to those for singleplex. There were no substantial differences in the sensitivity and specificity between these multiplex and singleplex real-time PCR assays. |
Standards for epidemiologic studies and surveillance of epilepsy
Thurman DJ , Beghi E , Begley CE , Berg AT , Buchhalter JR , Ding D , Hesdorffer DC , Hauser WA , Kazis L , Kobau R , Kroner B , Labiner D , Liow K , Logroscino G , Medina MT , Newton CR , Parko K , Paschal A , Preux PM , Sander JW , Selassie A , Theodore W , Tomson T , Wiebe S . Epilepsia 2011 52 2-26 Worldwide, about 65 million people are estimated to have epilepsy. Epidemiologic studies are necessary to define the full public health burden of epilepsy; to set public health and health care priorities; to provide information needed for prevention, early detection, and treatment; to identify education and service needs; and to promote effective health care and support programs for people with epilepsy. However, different definitions and epidemiologic methods complicate the tasks of these studies and their interpretations and comparisons. The purpose of this document is to promote consistency in definitions and methods in an effort to enhance future population-based epidemiologic studies, facilitate comparison between populations, and encourage the collection of data useful for the promotion of public health. We discuss: (1) conceptual and operational definitions of epilepsy, (2) data resources and recommended data elements, and (3) methods and analyses appropriate for epidemiologic studies or the surveillance of epilepsy. Variations in these are considered, taking into account differing resource availability and needs among countries and differing purposes among studies. 2011 International League Against Epilepsy. |
Haemophilus influenzae type b infection, vaccination, and H. influenzae carriage in children in Minnesota, 2008-2009
Lowther SA , Shinoda N , Juni BA , Theodore MJ , Wang X , Jawahir SL , Jackson ML , Cohn A , Danila R , Lynfield R . Epidemiol Infect 2011 140 (3) 1-9 An increase in invasive Haemophilus influenzae type b (Hib) cases occurred in Minnesota in 2008 after the recommended deferral of the 12-15 months Hib vaccine boosters during a US vaccine shortage. Five invasive Hib cases (one death) occurred in children; four had incomplete Hib vaccination (three refused/delayed); one was immunodeficient. Subsequently, we evaluated Hib carriage and vaccination. From 18 clinics near Hib cases, children (aged 4 weeks-60 months) were surveyed for pharyngeal Hib carriage. Records were compared for Hib, diphtheria-tetanus-acellular pertussis (DTaP), and pneumococcal (PCV-7) vaccination. Parents completed questionnaires on carriage risk factors and vaccination beliefs. In 1631 children (February-March 2009), no Hib carriage was detected; Hib vaccination was less likely to be completed than DTaP and PCV-7. Non-type b H. influenzae, detected in 245 (15%) children, was associated with: male sex, age 24-60 months, daycare attendance >15 h/week, a household smoker, and Asian/Pacific Islander race/ethnicity. In 2009, invasive Hib disease occurred in two children caused by the same strain that circulated in 2008. Hib remains a risk for vulnerable/unvaccinated children, although Hib carriage is not widespread in young children. |
sodC-based real-time PCR for detection of Neisseria meningitidis.
Dolan Thomas J , Hatcher CP , Satterfield DA , Theodore MJ , Bach MC , Linscott KB , Zhao X , Wang X , Mair R , Schmink S , Arnold KE , Stephens DS , Harrison LH , Hollick RA , Andrade AL , Lamaro-Cardoso J , de Lemos AP , Gritzfeld J , Gordon S , Soysal A , Bakir M , Sharma D , Jain S , Satola SW , Messonnier NE , Mayer LW . PLoS One 2011 6 (5) e19361 Real-time PCR (rt-PCR) is a widely used molecular method for detection of Neisseria meningitidis (Nm). Several rt-PCR assays for Nm target the capsule transport gene, ctrA. However, over 16% of meningococcal carriage isolates lack ctrA, rendering this target gene ineffective at identification of this sub-population of meningococcal isolates. The Cu-Zn superoxide dismutase gene, sodC, is found in Nm but not in other Neisseria species. To better identify Nm, regardless of capsule genotype or expression status, a sodC-based TaqMan rt-PCR assay was developed and validated. Standard curves revealed an average lower limit of detection of 73 genomes per reaction at cycle threshold (C(t)) value of 35, with 100% average reaction efficiency and an average R(2) of 0.9925. 99.7% (624/626) of Nm isolates tested were sodC-positive, with a range of average C(t) values from 13.0 to 29.5. The mean sodC C(t) value of these Nm isolates was 17.6+/-2.2 (+/-SD). Of the 626 Nm tested, 178 were nongroupable (NG) ctrA-negative Nm isolates, and 98.9% (176/178) of these were detected by sodC rt-PCR. The assay was 100% specific, with all 244 non-Nm isolates testing negative. Of 157 clinical specimens tested, sodC detected 25/157 Nm or 4 additional specimens compared to ctrA and 24 more than culture. Among 582 carriage specimens, sodC detected Nm in 1 more than ctrA and in 4 more than culture. This sodC rt-PCR assay is a highly sensitive and specific method for detection of Nm, especially in carriage studies where many meningococcal isolates lack capsule genes. |
Detection of bacterial pathogens in Mongolia meningitis surveillance with a new real-time PCR assay to detect Haemophilus influenzae.
Wang X , Mair R , Hatcher C , Theodore MJ , Edmond K , Wu HM , Harcourt BH , Carvalho MD , Pimenta F , Nymadawa P , Altantsetseg D , Kirsch M , Satola SW , Cohn A , Messonnier NE , Mayer LW . Int J Med Microbiol 2011 301 (4) 303-9 Since the implementation of Haemophilus influenzae (Hi) serotype b vaccine, other serotypes and non-typeable strains have taken on greater importance as a cause of Hi diseases. A rapid and accurate method is needed to detect all Hi regardless of the encapsulation status. We developed 2 real-time PCR (rt-PCR) assays to detect specific regions of the protein D gene (hpd). Both hpd assays are very specific and sensitive for detection of Hi. Of the 63 non-Hi isolates representing 21 bacterial species, none was detected by the hpd #1 assay, and only one of 2 H. aphrophilus isolates was detected by the hpd #3 assay. The hpd #1 and #3 assays detected 97% (229/237) and 99% (234/237) of Hi isolates, respectively, and were superior for detection of both typeable and non-typeable Hi isolates, as compared to previously developed rt-PCR targeting ompP2 or bexA. The diagnostic sensitivity and specificity of these rt-PCR assays were assessed on cerebrospinal fluid specimens collected as part of meningitis surveillance in Ulaanbaatar, Mongolia. The etiology (Neisseria meningitidis, Hi, and Streptococcus pneumoniae) of 111 suspected meningitis cases was determined by conventional methods (culture and latex agglutination), previously developed rt-PCR assays, and the new hpd assays. The rt-PCR assays were more sensitive for detection of meningitis pathogens than other classical methods and improved detection from 50% (56/111) to 75% (83/111). The hpd #3 assay identified a non-b Hi that was missed by the bexA assay and other methods. A sensitive rt-PCR assay to detect both typeable and non-typeable Hi is a useful tool for improving Hi disease surveillance especially after Hib vaccine introduction. |
STD screening of HIV-infected MSM in HIV clinics
Hoover KW , Butler M , Workowski K , Carpio F , Follansbee S , Gratzer B , Hare B , Johnston B , Theodore JL , Wohlfeiler M , Tao G , Brooks JT , Chorba T , Irwin K , Kent CK . Sex Transm Dis 2010 37 (12) 771-6 BACKGROUND: National guidelines for the care of human immunodeficiency virus (HIV)-infected persons recommend asymptomatic routine screening for sexually transmitted diseases (STDs). Our objective was to determine whether providers who care for HIV-infected men who have sex with men (MSM) followed these guidelines. METHODS: We abstracted medical records to evaluate STD screening at 8 large HIV clinics in 6 US cities. We estimated the number of men who had at least one test for syphilis, chlamydia (urethral and/or rectal), or gonorrhea (urethral, rectal, and/or pharyngeal) in 2004, 2005, and 2006. Urethral testing included nucleic acid amplification tests of both urethral swabs and urine. We also calculated the positivity of syphilis, chlamydia, and gonorrhea among screened men. RESULTS: Medical records were abstracted for 1334 HIV-infected MSM who made 14,659 visits from 2004-2006. The annual screening rate for syphilis ranged from 66.0% to 75.8% during 2004-2006. Rectal chlamydia and rectal and pharyngeal gonorrhea annual screening rates ranged from 2.3% to 8.5% despite moderate to high positivity among specimens from asymptomatic patients (3.0%-9.8%) during this period. Annual urethral chlamydia and gonorrhea screening rates were higher than rates for nonurethral sites, but were suboptimal, and ranged from 13.8% to 18.3%. CONCLUSIONS: Most asymptomatic HIV-infected MSM were screened for syphilis, indicating good provider adherence to this screening guideline. Low screening rates for gonorrhea and chlamydia, especially at rectal and pharyngeal sites, suggest that substantial barriers exist for complying with these guidelines. The moderate to high prevalence of asymptomatic chlamydial and gonococcal infections underscores the importance of screening. A range of clinical quality improvement interventions are needed to increase screening, including increasing the awareness of nucleic acid amplification tests for nonurethral screening. |
Changes in Neisseria meningitidis disease epidemiology in the United States, 1998-2007: implications for prevention of meningococcal disease
Cohn AC , MacNeil JR , Harrison LH , Hatcher C , Theodore J , Schmidt M , Pondo T , Arnold KE , Baumbach J , Bennett N , Craig AS , Farley M , Gershman K , Petit S , Lynfield R , Reingold A , Schaffner W , Shutt KA , Zell ER , Mayer LW , Clark T , Stephens D , Messonnier NE . Clin Infect Dis 2010 50 (2) 184-91 BACKGROUND: In January 2005, a quadrivalent (serogroups A, C , Y, and W-135) meningococcal conjugate vaccine was licensed for use in adolescents. This report describes the epidemiologic features of meningococcal disease in the United States from January 1998 through December 2007, before and during implementation of adolescent quadrivalent meningococcal conjugate vaccination. METHODS: Data were collected from active surveillance for invasive Neisseria meningitidis conducted through the Active Bacterial Core surveillance (ABCs) sites during 1998-2007. Isolates from cases were serogrouped at the ABCs site and confirmed at the Centers for Disease Control and Prevention. Estimates of the incidence and number of cases in the 50 states were calculated, standardizing for race and age group. RESULTS: In the period 1998-2007, a total of 2262 cases of meningococcal disease were reported from ABCs sites; 11.3% of these cases were fatal. The estimated United States average annual incidence of meningococcal disease was 0.53 cases per 100,000 population (95% confidence interval, 0.51-0.55), and an estimated 1525 (95% confidence interval, 1470-1598) cases occurred annually. The annual incidence decreased 64.1%, from 0.92 cases per 100,000 population in 1998 to 0.33 cases per 100,000 population in 2007. Infants aged <1 year have the highest incidence of meningococcal disease (5.38 cases per 100,000 population). After introduction of the quadrivalent meningococcal conjugate vaccine, no significant decrease in serogroup C or Y meningococcal disease was seen among those aged 11-19 years in 2006-2007, compared with 2004-2005. CONCLUSIONS: Before the introduction of the quadrivalent meningococcal conjugate vaccine, the incidence of meningococcal disease in the United States decreased to a historic low. However, meningococcal disease still causes a substantial burden of disease among all age groups. Future vaccination strategies may include targeting infants and preventing serogroup B meningococcal disease. |
Disparities in epilepsy: report of a systematic review by the North American Commission of the International League Against Epilepsy
Burneo JG , Jette N , Theodore W , Begley C , Parko K , Thurman DJ , Wiebe S , Task Force on Disparities in Epilepsy Care , North American Commission of the International League Against Epilepsy . Epilepsia 2009 50 (10) 2285-95 PURPOSE: We undertook a systematic review of the evidence on disparities in epilepsy with a focus on North American data (Canada, United States, and the English-speaking Caribbean). METHODS: We identified and evaluated: access to and outcomes following medical and surgical treatment, disability, incidence and prevalence, and knowledge and attitudes. An exhaustive search (1965-2007) was done, including: (1) disparities by socioeconomic status (SES), race/ethnicity, age, or education of subgroups of the epilepsy population; or (2) disparities between people with epilepsy (PWE) and healthy people or with other chronic illnesses. RESULTS: From 1,455 citations, 278 eligible abstracts were identified and 44 articles were reviewed. Comparative research data were scarce in all areas. PWE have been shown to have lower education and employment status; among PWE, differences in access to surgery have been shown by racial/ethnic groups. Aboriginals, women, and children have been shown to differ in use of health resources. Poor compliance has been shown to be associated with lower SES, insufficient insurance, poor relationship with treating clinicians, and not having regular responsibilities. DISCUSSION: Comprehensive, comparative research on all aspects of disparities in epilepsy is needed to understand the causes of disparities and the development of any policies aimed at addressing health disparities and minimizing their impact. |
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