Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-14 (of 14 Records) |
Query Trace: Lehmann T [original query] |
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Effectiveness of 2 and 3 mRNA COVID-19 Vaccines Doses against Omicron and Delta-Related Outpatient Illness among Adults, October 2021 - February 2022 (preprint)
Kim SS , Chung JR , Talbot HK , Grijalva CG , Wernli KJ , Martin ET , Monto AS , Belongia EA , McLean HQ , Gaglani M , Mamawala M , Nowalk MP , Geffel KM , Tartof SY , Florea A , Lee JS , Tenforde MW , Patel MM , Flannery B , Bentz ML , Burgin A , Burroughs M , Davis ML , Howard D , Lacek K , Madden JC , Nobles S , Padilla J , Sheth M , Arroliga A , Beeram M , Dunnigan K , Ettlinger J , Graves A , Hoffman E , Jatla M , McKillop A , Murthy K , Mutnal M , Priest E , Raiyani C , Rao A , Requenez L , Settele N , Smith M , Stone K , Thomas J , Volz M , Walker K , Zayed M , Annan E , Daley P , Kniss K , Merced-Morales A , Ayala E , Amundsen B , Aragones M , Calderon R , Hong V , Jimenez G , Kim J , Ku J , Lewin B , McDaniel A , Reyes A , Shaw S , Takhar H , Torres A , Burganowski R , Kiniry E , Moser KA , Nguyen M , Park S , Wellwood S , Wickersham B , Alvarado-Batres J , Benz S , Berger H , Bissonnette A , Blake J , Boese K , Botten E , Boyer J , Braun M , Breu B , Burbey G , Cravillion C , Delgadillo C , Donnerbauer A , Dziedzic T , Eddy J , Edgren H , Ermeling A , Ewert K , Fehrenbach C , Fernandez R , Frome W , Guzinski S , Heeren L , Herda D , Hertel M , Heuer G , Higdon E , Ivacic L , Jepsen L , Kaiser S , Karl J , Keffer B , King J , Koepel TK , Kohl S , Kohn S , Kohnhorst D , Kronholm E , Le T , Lemieux A , Marcis C , Maronde M , McCready I , McGreevey K , Meece J , Mehta N , Miesbauer D , Moon V , Moran J , Nikolai C , Olson B , Olstadt J , Ott L , Pan N , Pike C , Polacek D , Presson M , Price N , Rayburn C , Reardon C , Rotar M , Rottscheit C , Salzwedel J , Saucedo J , Scheffen K , Schug C , Seyfert K , Shrestha R , Slenczka A , Stefanski E , Strupp M , Tichenor M , Watkins L , Zachow A , Zimmerman B , Bauer S , Beney K , Cheng CK , Faraj N , Getz A , Grissom M , Groesbeck M , Harrison S , Henson K , Jermanus K , Johnson E , Kaniclides A , Kimberly A , Lamerato LE , Lauring A , Lehmann-Wandell R , McSpadden EJ , Nabors L , Truscon R , Balasubramani GK , Bear T , Bobeck J , Bowser E , Clarke K , Clarke LG , Dauer K , Deluca C , Dierks B , Haynes L , Hickey R , Johnson M , Jonsson A , Luosang N , McKown L , Peterson A , Phaturos D , Rectenwald A , Sax TM , Stiegler M , Susick M , Suyama J , Taylor L , Walters S , Weissman A , Williams JV , Blair M , Carter J , Chappell J , Copen E , Denney M , Graes K , Halasa N , Lindsell C , Liu Z , Longmire S , McHenry R , Short L , Tan HN , Vargas D , Wrenn J , Wyatt D , Zhu Y . medRxiv 2022 10 Background: We estimated SARS-CoV-2 Delta and Omicron-specific effectiveness of 2 and 3 mRNA COVID-19 vaccine doses in adults against symptomatic illness in US outpatient settings. Method(s): Between October 1, 2021, and February 12, 2022, research staff consented and enrolled eligible participants who had fever, cough, or loss of taste or smell and sought outpatient medical care or clinical SARS-CoV-2 testing within 10 days of illness onset. Using the test-negative design, we compared the odds of receiving 2 or 3 mRNA COVID-19 vaccine doses among SARS-CoV-2 cases versus controls using logistic regression. Regression models were adjusted for study site, age, onset week, and prior SARS-CoV-2 infection. Vaccine effectiveness (VE) was calculated as (1 - adjusted odds ratio) x 100%. Result(s): Among 3847 participants included for analysis, 574 (32%) of 1775 tested positive for SARS-CoV-2 during the Delta predominant period and 1006 (56%) of 1794 participants tested positive during the Omicron predominant period. When Delta predominated, VE against symptomatic illness in outpatient settings was 63% (95% CI: 51% to 72%) among mRNA 2-dose recipients and 96% (95% CI: 93% to 98%) for 3-dose recipients. When Omicron predominated, VE was 21% (95% CI: -6% to 41%) among 2-dose recipients and 62% (95% CI: 48% to 72%) among 3-dose recipients. Conclusion(s): In this adult population, 3 mRNA COVID-19 vaccine doses provided substantial protection against symptomatic illness in outpatient settings when the Omicron variant became the predominant cause of COVID-19 in the U.S. These findings support the recommendation for a 3rd mRNA COVID-19 vaccine dose. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Consensus on the key characteristics of immunotoxic agents as a basis for hazard identification
Germolec DR , Lebrec H , Anderson SE , Burleson GR , Cardenas A , Corsini E , Elmore SE , Kaplan BLF , Lawrence BP , Lehmann GM , Maier CC , McHale CM , Myers LP , Pallardy M , Rooney AA , Zeise L , Zhang L , Smith MT . Environ Health Perspect 2022 130 (10) 105001 BACKGROUND: Key characteristics (KCs), properties of agents or exposures that confer potential hazard, have been developed for carcinogens and other toxicant classes. KCs have been used in the systematic assessment of hazards and to identify assay and data gaps that limit screening and risk assessment. Many of the mechanisms through which pharmaceuticals and occupational or environmental agents modulate immune function are well recognized. Thus KCs could be identified for immunoactive substances and applied to improve hazard assessment of immunodulatory agents. OBJECTIVES: The goal was to generate a consensus-based synthesis of scientific evidence describing the KCs of agents known to cause immunotoxicity and potential applications, such as assays to measure the KCs. METHODS: A committee of 18 experts with diverse specialties identified 10 KCs of immunotoxic agents, namely, 1) covalently binds to proteins to form novel antigens, 2) affects antigen processing and presentation, 3) alters immune cell signaling, 4) alters immune cell proliferation, 5) modifies cellular differentiation, 6) alters immune cell-cell communication, 7) alters effector function of specific cell types, 8) alters immune cell trafficking, 9) alters cell death processes, and 10) breaks down immune tolerance. The group considered how these KCs could influence immune processes and contribute to hypersensitivity, inappropriate enhancement, immunosuppression, or autoimmunity. DISCUSSION: KCs can be used to improve efforts to identify agents that cause immunotoxicity via one or more mechanisms, to develop better testing and biomarker approaches to evaluate immunotoxicity, and to enable a more comprehensive and mechanistic understanding of adverse effects of exposures on the immune system. https://doi.org/10.1289/EHP10800. |
Emergence of a multidrug-resistant and virulent Streptococcus pneumoniae lineage mediates serotype replacement after PCV13: an international whole-genome sequencing study.
Lo SW , Mellor K , Cohen R , Alonso AR , Belman S , Kumar N , Hawkins PA , Gladstone RA , von Gottberg A , Veeraraghavan B , Ravikumar KL , Kandasamy R , Pollard SAJ , Saha SK , Bigogo G , Antonio M , Kwambana-Adams B , Mirza S , Shakoor S , Nisar I , Cornick JE , Lehmann D , Ford RL , Sigauque B , Turner P , Moïsi J , Obaro SK , Dagan R , Diawara I , SkoczyĆska A , Wang H , Carter PE , Klugman KP , Rodgers G , Breiman RF , McGee L , Bentley SD , Almagro CM , Varon E . Lancet Microbe 2022 3 (10) e735-e743 BACKGROUND: Serotype 24F is one of the emerging pneumococcal serotypes after the introduction of pneumococcal conjugate vaccine (PCV). We aimed to identify lineages driving the increase of serotype 24F in France and place these findings into a global context. METHODS: Whole-genome sequencing was performed on a collection of serotype 24F pneumococci from asymptomatic colonisation (n=229) and invasive disease (n=190) isolates among individuals younger than 18 years in France, from 2003 to 2018. To provide a global context, we included an additional collection of 24F isolates in the Global Pneumococcal Sequencing (GPS) project database for analysis. A Global Pneumococcal Sequence Cluster (GPSC) and a clonal complex (CC) were assigned to each genome. Phylogenetic, evolutionary, and spatiotemporal analysis were conducted using the same 24F collection and supplemented with a global collection of genomes belonging to the lineage of interest from the GPS project database (n=25 590). FINDINGS: Serotype 24F was identified in numerous countries mainly due to the clonal spread of three lineages: GPSC10 (CC230), GPSC16 (CC156), and GPSC206 (CC7701). GPSC10 was the only multidrug-resistant lineage. GPSC10 drove the increase in 24F in France and had high invasive disease potential. The international dataset of GPSC10 (n=888) revealed that this lineage expressed 16 other serotypes, with only six included in 13-valent PCV (PCV13). All serotype 24F isolates were clustered in a single clade within the GPSC10 phylogeny and long-range transmissions were detected from Europe to other continents. Spatiotemporal analysis showed GPSC10-24F took 3-5 years to spread across France and a rapid change of serotype composition from PCV13 serotype 19A to 24F during the introduction of PCV13 was observed in neighbouring country Spain. INTERPRETATION: Our work reveals that GPSC10 alone is a challenge for serotype-based vaccine strategy. More systematic investigation to identify lineages like GPSC10 will better inform and improve next-generation preventive strategies against pneumococcal diseases. FUNDING: Bill & Melinda Gates Foundation, Wellcome Sanger Institute, and the US Centers for Disease Control and Prevention. |
Distinct Streptococcus pneumoniae cause invasive disease in Papua New Guinea.
Mellor KC , Lo S , Yoannes M , Michael A , Orami T , Greenhill AR , Breiman RF , Hawkins P , McGee L , Bentley SD , Ford RL , Lehmann D . Microb Genom 2022 8 (7) Streptococcus pneumoniae is a key contributor to childhood morbidity and mortality in Papua New Guinea (PNG). For the first time, whole genome sequencing of 174 isolates has enabled detailed characterisation of diverse S. pneumoniae causing invasive disease in young children in PNG, 1989-2014. This study captures the baseline S. pneumoniae population prior to the introduction of 13-valent pneumococcal conjugate vaccine (PCV13) into the national childhood immunisation programme in 2014. Relationships amongst lineages, serotypes and antimicrobial resistance traits were characterised, and the population was viewed in the context of a global collection of isolates. The analyses highlighted adiverse S. pneumoniae population associated with invasive disease in PNG, with 45 unique Global Pneumococcal Sequence Clusters (GPSCs) observed amongst the 174 isolates reflecting multiple lineages observed in PNG that have not been identified in other geographic locations. The majority of isolates were from children with meningitis, of which 52% (n=72) expressed non-PCV13 serotypes. Over a third of isolates were predicted to be resistant to at least one antimicrobial. PCV13 serotype isolates had 10.1 times the odds of being multidrug-resistant (MDR) compared to non-vaccine serotype isolates, and no isolates with GPSCs unique to PNG were MDR. Serotype 2 was the most commonly identified serotype; we identified a highly clonal cluster of serotype 2 isolates unique to PNG, and a distinct second cluster indicative of long-distance transmission. Ongoing surveillance, including whole-genome sequencing, is needed to ascertain the impact of the national PCV13 programme upon the S. pneumoniae population, including serotype replacement and antimicrobial resistance traits. |
Current breast milk PFAS levels in the United States and Canada: After all this time, why don't we know more
LaKind JS , Verner MA , Rogers RD , Goeden H , Naiman DQ , Marchitti SA , Lehmann GM , Hines EP , Fenton SE . Environ Health Perspect 2022 130 (2) 25002 BACKGROUND: Despite 20 y of biomonitoring studies of per- and polyfluoroalkyl substances (PFAS) in both serum and urine, we have an extremely limited understanding of PFAS concentrations in breast milk of women from the United States and Canada. The lack of robust information on PFAS concentrations in breast milk and implications for breastfed infants and their families were brought to the forefront by communities impacted by PFAS contamination. OBJECTIVES: The objectives of this work are to: a) document published PFAS breast milk concentrations in the United States and Canada; b) estimate breast milk PFAS levels from maternal serum concentrations in national surveys and communities impacted by PFAS; and c) compare measured/estimated milk PFAS concentrations to screening values. METHODS: We used three studies reporting breast milk concentrations in the United States and Canada We also estimated breast milk PFAS concentrations by multiplying publicly available serum concentrations by milk:serum partitioning ratios for perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS), and perfluorononanoic acid (PFNA). Measured and estimated breast milk concentrations were compared to children's drinking water screening values. DISCUSSION: Geometric means of estimated breast milk concentrations ranged over approximately two orders of magnitude for the different surveys/communities. All geometric mean and mean estimated and measured breast milk PFOA and PFOS concentrations exceeded drinking water screening values for children, sometimes by more than two orders of magnitude. For PFHxS and PFNA, all measured breast milk levels were below the drinking water screening values for children; the geometric mean estimated breast milk concentrations were close to-or exceeded-the children's drinking water screening values for certain communities. Exceeding a children's drinking water screening value does not indicate that adverse health effects will occur and should not be interpreted as a reason to not breastfeed; it indicates that the situation should be further evaluated. It is past time to have a better understanding of environmental chemical transfer to-and concentrations in-an exceptional source of infant nutrition. https://doi.org/10.1289/EHP10359. |
International links between Streptococcus pneumoniae vaccine serotype 4 sequence type (ST) 801 in Northern European shipyard outbreaks of invasive pneumococcal disease.
Gladstone RA , Siira L , Brynildsrud OB , Vestrheim DF , Turner P , Clarke SC , Srifuengfung S , Ford R , Lehmann D , Egorova E , Voropaeva E , Haraldsson G , Kristinsson KG , McGee L , Breiman RF , Bentley SD , Sheppard CL , Fry NK , Corander J , Toropainen M , Steens A . Vaccine 2022 40 (7) 1054-1060 BACKGROUND: Pneumococcal disease outbreaks of vaccine preventable serotype 4 sequence type (ST)801 in shipyards have been reported in several countries. We aimed to use genomics to establish any international links between them. METHODS: Sequence data from ST801-related outbreak isolates from Norway (n = 17), Finland (n = 11) and Northern Ireland (n = 2) were combined with invasive pneumococcal disease surveillance from the respective countries, and ST801-related genomes from an international collection (n = 41 of > 40,000), totalling 106 genomes. Raw data were mapped and recombination excluded before phylogenetic dating. RESULTS: Outbreak isolates were relatively diverse, with up to 100 SNPs (single nucleotide polymorphisms) and a common ancestor estimated around the year 2000. However, 19 Norwegian and Finnish isolates were nearly indistinguishable (0-2 SNPs) with the common ancestor dated around 2017. CONCLUSION: The total diversity of ST801 within the outbreaks could not be explained by recent transmission alone, suggesting that harsh environmental and associated living conditions reported in the shipyards may facilitate invasion of colonising pneumococci. However, near identical strains in the Norwegian and Finnish outbreaks does suggest that transmission between international shipyards also contributed to those outbreaks. This indicates the need for improved preventative measures in this working population including pneumococcal vaccination. |
Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents
Wolraich ML , Hagan JFJr , Allan C , Chan E , Davison D , Earls M , Evans SW , Flinn SK , Froehlich T , Frost J , Holbrook JR , Lehmann CU , Lessin HR , Okechukwu K , Pierce KL , Winner JD , Zurhellen W . Pediatrics 2019 144 (4) Attention-deficit/hyperactivity disorder (ADHD) is 1 of the most common neurobehavioral disorders of childhood and can profoundly affect children's academic achievement, well-being, and social interactions. The American Academy of Pediatrics first published clinical recommendations for evaluation and diagnosis of pediatric ADHD in 2000; recommendations for treatment followed in 2001. The guidelines were revised in 2011 and published with an accompanying process of care algorithm (PoCA) providing discrete and manageable steps by which clinicians could fulfill the clinical guideline's recommendations. Since the release of the 2011 guideline, the Diagnostic and Statistical Manual of Mental Disorders has been revised to the fifth edition, and new ADHD-related research has been published. These publications do not support dramatic changes to the previous recommendations. Therefore, only incremental updates have been made in this guideline revision, including the addition of a key action statement related to diagnosis and treatment of comorbid conditions in children and adolescents with ADHD. The accompanying process of care algorithm has also been updated to assist in implementing the guideline recommendations. Throughout the process of revising the guideline and algorithm, numerous systemic barriers were identified that restrict and/or hamper pediatric clinicians' ability to adopt their recommendations. Therefore, the subcommittee created a companion article (available in the Supplemental Information) on systemic barriers to the care of children and adolescents with ADHD, which identifies the major systemic-level barriers and presents recommendations to address those barriers; in this article, we support the recommendations of the clinical practice guideline and accompanying process of care algorithm. |
Notes from the Field: Cronobacter sakazakii meningitis in a full-term neonate fed exclusively with breast milk - Indiana, 2018
Sundararajan M , Enane LA , Kidwell LA , Gentry R , Danao S , Bhumbra S , Lehmann C , Teachout M , Yeadon-Fagbohun J , Krombach P , Schroeder B , Martin H , Winkjer J , Waltz T , Strysko J , Cope JR . MMWR Morb Mortal Wkly Rep 2018 67 (44) 1248-1249 In January 2018, the Indiana State Department of Health (ISDH) was notified of a case of Cronobacter sakazakii meningitis in a female neonate who had been fed exclusively maternal breast milk. The infant was born by induced vaginal delivery at 37 weeks’ gestational age. She was discharged from the newborn nursery after 2 days and was clinically well until age 8 days, when she was admitted with poor feeding, fever of 100.4°F (38°C), and abnormal movements. Electroencephalography demonstrated multifocal seizures; MRI demonstrated multifocal restricted diffusion, leptomeningeal enhancement, and patchy hemorrhagic areas. Cultures from blood and cerebrospinal fluid yielded C. sakazakii, a gram-negative pathogenic bacillus. She was initially treated with meropenem, gentamicin, and antiepileptics to control seizures; when antibiotic sensitivity results were available, the antimicrobial regimen was narrowed to cefepime to complete a 21-day course. She was discharged home at age 33 days with early intervention therapies for global hypotonia and close monitoring of her development. |
Skin sensitization testing needs and data uses by US regulatory and research agencies
Strickland J , Daniel AB , Allen D , Aguila C , Ahir S , Bancos S , Craig E , Germolec D , Ghosh C , Hudson NL , Jacobs A , Lehmann DM , Matheson J , Reinke EN , Sadrieh N , Vukmanovic S , Kleinstreuer N . Arch Toxicol 2018 93 (2) 273-291 United States regulatory and research agencies may rely upon skin sensitization test data to assess the sensitization hazards associated with dermal exposure to chemicals and products. These data are evaluated to ensure that such substances will not cause unreasonable adverse effects to human health when used appropriately. The US Consumer Product Safety Commission, the US Environmental Protection Agency, the US Food and Drug Administration, the Occupational Safety and Health Administration, the National Institute for Occupational Safety and Health, and the US Department of Defense are member agencies of the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM). ICCVAM seeks to identify opportunities for the use of non-animal replacements to satisfy these testing needs and requirements. This review identifies the standards, test guidelines, or guidance documents that are applicable to satisfy each of these agency's needs; the current use of animal testing and flexibility for using alternative methodologies; information needed from alternative tests to fulfill the needs for skin sensitization data; and whether data from non-animal alternative approaches are accepted by these US federal agencies. |
Respirator use in a hospital setting: Establishing surveillance metrics
Yarbrough MI , Ficken ME , Lehmann CU , Talbot TR , Swift MD , McGown PW , Wheaton RF , Bruer M , Little SW , Oke CA . J Int Soc Respir Prot 2016 33 (1) 1-11 Information that details use and supply of respirators in acute care hospitals is vital to prevent disease transmission, assure the safety of health care personnel, and inform national guidelines and regulations. OBJECTIVE: To develop measures of respirator use and supply in the acute care hospital setting to aid evaluation of respirator programs, allow benchmarking among hospitals, and serve as a foundation for national surveillance to enhance effective Personal Protective Equipment (PPE) use and management. METHODS: We identified existing regulations and guidelines that govern respirator use and supply at Vanderbilt University Medical Center (VUMC). Related routine and emergency hospital practices were documented through an investigation of hospital administrative policies, protocols, and programs. Respirator dependent practices were categorized based on hospital workflow: Prevention (preparation), patient care (response), and infection surveillance (outcomes). Associated data in information systems were extracted and their quality evaluated. Finally, measures representing major factors and components of respirator use and supply were developed. RESULTS: Various directives affecting multiple stakeholders govern respirator use and supply in hospitals. Forty-seven primary and secondary measures representing factors of respirator use and supply in the acute care hospital setting were derived from existing information systems associated with the implementation of these directives. CONCLUSION: Adequate PPE supply and effective use that limit disease transmission and protect health care personnel are dependent on multiple factors associated with routine and emergency hospital practices. We developed forty-seven measures that may serve as the basis for a national PPE surveillance system, beginning with standardized measures of respirator use and supply for collection across different hospital types, sizes, and locations to inform hospitals, government agencies, manufacturers, and distributors. Despite involvement of multiple hospital stakeholders, regulatory guidance prescribes workplace practices that are likely to result in similar workflows across hospitals. Future work will explore the feasibility of implementing the collection and reporting of standardized measures in multiple facilities. |
Evaluation of the impact of National HIV Testing Day - United States, 2011-2014
Lecher SL , Hollis N , Lehmann C , Hoover KW , Jones A , Belcher L . MMWR Morb Mortal Wkly Rep 2016 65 (24) 613-8 Human immunodeficiency virus (HIV) testing is the first step in the continuum of HIV prevention, care, and treatment services, without which, gaps in HIV diagnosis cannot be addressed. National HIV testing campaigns are useful for promoting HIV testing among large numbers of persons. However, the impact of such campaigns on identification of new HIV-positive diagnoses is unclear. To assess whether National HIV Testing Day (NHTD, June 27) was effective in identifying new HIV-positive diagnoses, National HIV Prevention Program Monitoring and Evaluation (NHM&E) data for CDC-funded testing events conducted during 2011-2014 were analyzed. The number of HIV testing events and new HIV-positive diagnoses during June of each year were compared with those in other months by demographics and target populations. The number of HIV testing events and new HIV-positive diagnoses were also compared for each day leading up to and after NHTD in June and July of each year. New HIV-positive diagnoses peaked in June relative to other months and specifically on NHTD. During 2011-2014, NHTD had a substantial impact on increasing the number of persons who knew their HIV status and in diagnosing new HIV infections. NHTD also proved effective in reaching persons at high risk disproportionately affected by HIV, including African American (black) men, men who have sex with men (MSM), and transgender persons. Promoting NHTD can successfully increase the number of new HIV-positive diagnoses, including HIV infections among target populations at high risk for HIV infection. |
Toxoplasmosis in sentinel chickens (Gallus domesticus) in New England farms: seroconversion, distribution of tissue cysts in brain, heart, and skeletal muscle by bioassay in mice and cats
Dubey JP , Lehmann T , Lautner F , Kwok OC , Gamble HR . Vet Parasitol 2015 214 55-8 Free-range chickens are a good indicator of soil contamination with oocysts because they feed from the ground and they are also an important source of infection for cats that in turn shed oocysts after eating tissues of intermediate hosts. Little is known of the epidemiology of toxoplasmosis in chickens. In the present study 90 Toxoplasma gondii seronegative, sentinel chickens were placed on three (30 each) swine farms in New England in November, 2003. Chickens were bled monthly and their sera were tested for T. gondii antibodies by the modified agglutination test (MAT, cut-off 1:25). Chickens that seroconverted were euthanized and their tissues were bioassayed in mice, cats, or both. Over the course of the experiment (7 months), 31 of 71 chickens seroconverted (MAT 1:100 or higher). Tissues of 26 seropositive chickens were bioassayed in both cats and mice; viable T. gondii was isolated, by bioassay in mice, from hearts (whole) of all 26 chickens, brains (whole) of 3 chickens and leg muscles (25g) of 11 chickens; 21 of 26 cats fed 250g of muscle from seropositive chickens excreted T. gondii oocysts. Results indicated that the density of T. gondii in poultry muscle is low but heart is the tissue of choice for isolation of viable parasites. |
Sensitive assessment of the virologic outcomes of stopping and restarting non-nucleoside reverse transcriptase inhibitor-based antiretroviral therapy
Geretti AM , Fox Z , Johnson JA , Booth C , Lipscomb J , Stuyver LJ , Tachedjian G , Baxter J , Touloumi G , Lehmann C , Owen A , Phillips A . PLoS One 2013 8 (7) e69266 BACKGROUND: Non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant mutants have been shown to emerge after interruption of suppressive NNRTI-based antiretroviral therapy (ART) using routine testing. The aim of this study was to quantify the risk of resistance by sensitive testing and correlate the detection of resistance with NNRTI concentrations after treatment interruption and virologic responses after treatment resumption. METHODS: Resistance-associated mutations (RAMs) and NNRTI concentrations were studied in plasma from 132 patients who interrupted suppressive ART within SMART. RAMs were detected by Sanger sequencing, allele-specific PCR, and ultra-deep sequencing. NNRTI concentrations were measured by sensitive high-performance liquid chromatography. RESULTS: Four weeks after NNRTI interruption, 19/31 (61.3%) and 34/39 (87.2%) patients showed measurable nevirapine (>0.25 ng/ml) or efavirenz (>5 ng/ml) concentrations, respectively. Median eight weeks after interruption, 22/131 (16.8%) patients showed ≥1 NNRTI-RAM, including eight patients with NNRTI-RAMs detected only by sensitive testing. The adjusted odds ratio (OR) of NNRTI-RAM detection was 7.62 (95% confidence interval [CI] 1.52, 38.30; p = 0.01) with nevirapine or efavirenz concentrations above vs. below the median measured in the study population. Staggered interruption, whereby nucleos(t)ide reverse transcriptase inhibitors (NRTIs) were continued for median nine days after NNRTI interruption, did not prevent NNRTI-RAMs, but increased detection of NRTI-RAMs (OR 4.25; 95% CI 1.02, 17.77; p = 0.03). After restarting NNRTI-based ART (n = 90), virologic suppression rates <400 copies/ml were 8/13 (61.5%) with NNRTI-RAMs, 7/11 (63.6%) with NRTI-RAMs only, and 51/59 (86.4%) without RAMs. The ORs of re-suppression were 0.18 (95% CI 0.03, 0.89) and 0.17 (95% CI 0.03, 1.15) for patients with NNRTI-RAMs or NRTI-RAMs only respectively vs. those without RAMs (p = 0.04). CONCLUSIONS: Detection of resistant mutants in the rebound viremia after interruption of efavirenz- or nevirapine-based ART affects outcomes once these drugs are restarted. Further studies are needed to determine RAM persistence in untreated patients and impact on newer NNRTIs. |
Efficacy of a tetravalent chimeric dengue vaccine (DENVax) in cynomolgus macaques
Osorio JE , Brewoo JN , Silengo SJ , Arguello J , Moldovan IR , Tary-Lehmann M , Powell TD , Livengood JA , Kinney RM , Huang CY , Stinchcomb DT . Am J Trop Med Hyg 2011 84 (6) 978-87 Three tetravalent formulations of chimeric dengue (DENVax) viruses containing the pre-membrane and envelope genes of serotypes 1-4 expressed by the attenuated DENV-2 PDK-53 genome were tested for safety, immunogenicity, and efficacy in cynomolgus macaques (Macaca fascicularis). Subcutaneous injection of the DENVax formulations was well-tolerated. Low levels of viremia of only one of the four vaccine viruses were detected yet virus neutralizing antibody titers were induced against all four dengue virus serotypes after one or two administrations of vaccine. All animals immunized with the high-dose formulation were protected from viremia, and all immunized animals were completely protected from DENV-3 and DENV-4 challenge. A lower dose of DENVax formulation partially protected animals from DENV-1 or DENV-2 challenge. In contrast, all control animals developed high levels of viremia for multiple days after challenge with DENV 1-4. This study highlights the immunogenicity and efficacy of the tetravalent DENVax formulations in nonhuman primates. |
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