Last data update: May 13, 2024. (Total: 46773 publications since 2009)
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The Seattle Flu Study: a multi-arm community-based prospective study protocol for assessing influenza prevalence, transmission, and genomic epidemiology (preprint)
Chu HY , Boeckh M , Englund JA , Famulare M , Lutz B , Nickerson DA , Rieder M , Starita LM , Shendure J , Bedford T , Adler A , Brandstetter E , Frazer CD , Han PD , Gulati RK , Hadfield J , Jackson M , Kiavand A , Kimball LE , Lacombe K , Logue JK , Lyon VR , Newman KL , Sibley TR , Zigman Suchsland M , Wolf C . medRxiv 2020 2020.03.02.20029595 Introduction Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterize, and potentially contain new and emerging influenza strains at a population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population.Methods and Analysis Starting in the 2018-19 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses, and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modeling platforms are in development to characterize the regional spread of influenza and other respiratory pathogens.Ethics and Dissemination The study was approved by the University of Washington’s Institutional Review Board. Results will be disseminated through talks at conferences, peer-reviewed publications, and on the study website (www.seattleflu.org).Strengths and limitations of this study- Large-scale multiple-arm study of respiratory illness characterization with collection of samples from individuals in the community as well as in ambulatory care and hospital settings- Integration of sociodemographic, clinical, and geospatial data on a regional level- Multiplex molecular testing for multiple viral and bacterial pathogens and whole genome sequencing of influenza for detailed molecular epidemiologic characterization and transmission mapping- Geographically and socioeconomically diverse sampling of community-based acute respiratory illnessesCompeting Interest StatementAmanda Adler, Elisabeth Brandstetter, Michael Famulare, Chris D. Frazar, Peter D. Han, Reena K. Gulati, James Hadfield, Michael L. Jackson, Anahita Kiavand, Louise E. Kimball, Kirsten Lacombe, Jennifer Logue, Victoria Lyon, Kira L. Newman, Thomas R. Sibley, Jay Shendure, Lea Starita, Monica L. Zigman Suchsland, and Caitlin Wolf declare no competing interests. Helen Y Chu receives research support from Sanofi, Cepheid, and Genentech/Roche and is a consultant for Merck. Janet Englund receives research support to her institution from Astrazeneca, GlaxoSmithKline, Merck, and Novavax and is a consultant for Sanofi Pasteur and Meissa Vaccines.Funding StatementThe Seattle Flu Study is funded through the Brotman Baty Institute. The funder was not involved in the design of the study, does not have any ownership over the management and conduct of the study, the data, or the rights to publishAuthor DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable YesThe data will be accessed only by authorized individuals on the study team. Access to deidentified, aggregated data and analysis code will be publicly available on the study web page (www.seattleflu.org). http://www.seattleflu.org |
Meeting report: 36th international conference on antiviral research in Lyon, France, March 13-17, 2023
Spengler JR , Carter K , Delang L , Durantel D , Gowen BB , Herrero LJ , Hurst B , Janeba Z , Jordan R , Luo D , Meier C , Moffat J , Rocha-Pereira J , Seley-Radtke KL , Welch SR , Schang LM . Antiviral Res 2023 217 105678 The 36th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held March 13-17, 2023, in Lyon, France, and concurrently through an interactive remote meeting platform. Here we provide a report summarizing the presentations at the 36th ICAR, including the ISAR speaker awards. We also detail special events, sessions, and additional awards conferred at the meeting. ICAR returned to in-person meetings in 2022, convening in Seattle, WA, USA. The 36th ICAR is the first in-person meeting of the society in Europe since the beginning of the COVID-19 pandemic, which restricted most events to virtual attendance to help mitigate the spread and subsequent public health impact of SARS-CoV-2. An exceptionally high number of registrants and record attendance at this year's ICAR, along with a vast array of demonstrable expertise in a variety of antiviral research-related fields, reflected a strong and growing antiviral research community committed to improving health outcomes from viral diseases, including SARS-CoV-2, and to future pandemic preparedness. This report highlights the breadth of expertise, quality of research, and notable advancements that were contributed by members of ISAR and other participants at the meeting. ICAR aims to continue to provide a platform for sharing information, fostering collaborations, and supporting trainees in the field of antiviral research. The 37th ICAR will be held in Gold Coast, Australia, May 20-24, 2024. |
New Lineage of Lassa Virus, Togo, 2016.
Whitmer SLM , Strecker T , Cadar D , Dienes HP , Faber K , Patel K , Brown SM , Davis WG , Klena JD , Rollin PE , Schmidt-Chanasit J , Fichet-Calvet E , Noack B , Emmerich P , Rieger T , Wolff S , Fehling SK , Eickmann M , Mengel JP , Schultze T , Hain T , Ampofo W , Bonney K , Aryeequaye JND , Ribner B , Varkey JB , Mehta AK , Lyon GM 3rd , Kann G , De Leuw P , Schuettfort G , Stephan C , Wieland U , Fries JWU , Kochanek M , Kraft CS , Wolf T , Nichol ST , Becker S , Ströher U , Günther S . Emerg Infect Dis 2018 24 (3) 599-602 We describe a strain of Lassa virus representing a putative new lineage that was isolated from a cluster of human infections with an epidemiologic link to Togo. This finding extends the known range of Lassa virus to Togo. |
Meeting report: 35th international conference on antiviral research in Seattle, WA, USA - March 21-25, 2022.
Spengler JR , Welch SR , Deval J , Gentry BG , Brancale A , Carter K , Moffat J , Meier C , Seley-Radtke KL , Schang LM . Antiviral Res 2022 211 105521 The 35th International Conference on Antiviral Research (ICAR), sponsored by the International Society for Antiviral Research (ISAR), was held in Seattle, Washington, USA, on March 21-25, 2022 and concurrently through an interactive remote meeting platform. This report gives an overview of the conference on behalf of the society. It provides a general review of the meeting and awardees, summarizing the presentations and their main conclusions from the perspective of researchers active in many different areas of antiviral research and development. Through ICAR, leaders in the field of antiviral research were able to showcase their efforts, as participants learned about key advances in the field. The impact of these efforts was exemplified by many presentations on SARS-CoV-2 demonstrating the remarkable response to the ongoing pandemic, as well as future pandemic preparedness, by members of the antiviral research community. As we address ongoing outbreaks and seek to mitigate those in the future, this meeting continues to support outstanding opportunities for the exchange of knowledge and expertise while fostering cross-disciplinary collaborations in therapeutic and vaccine development. The 36th ICAR will be held in Lyon, France, March 13-17, 2023. |
Leveraging risk communication science across US federal agencies.
Klein WMP , Boutté AK , Brake H , Beal M , Lyon-Daniel K , Eisenhauer E , Grasso M , Hubbell B , Jenni KE , Lauer CJ , Lupia AW , Prue CE , Rausch P , Shapiro CD , Smith MD , Riley WT . Nat Hum Behav 2021 5 (4) 411-413 Many US federal agencies apply principles from risk communication science across a wide variety of hazards. In so doing, they identify key research and practice gaps that, if addressed, could help better serve the nation's communities and greatly enhance practice, research, and policy development. |
Risk Factors for Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Homeless Shelters in Chicago, Illinois-March-May, 2020.
Ghinai I , Davis ES , Mayer S , Toews KA , Huggett TD , Snow-Hill N , Perez O , Hayden MK , Tehrani S , Landi AJ , Crane S , Bell E , Hermes JM , Desai K , Godbee M , Jhaveri N , Borah B , Cable T , Sami S , Nozicka L , Chang YS , Jagadish A , Chee M , Thigpen B , Llerena C , Tran M , Surabhi DM , Smith ED , Remus RG , Staszcuk R , Figueroa E , Leo P , Detmer WM , Lyon E , Carreon S , Hoferka S , Ritger KA , Jasmin W , Nagireddy P , Seo JY , Fricchione MJ , Kerins JL , Black SR , Butler LM , Howard K , McCauley M , Fraley T , Arwady MA , Gretsch S , Cunningham M , Pacilli M , Ruestow PS , Mosites E , Avery E , Longcoy J , Lynch EB , Layden JE . Open Forum Infect Dis 2020 7 (11) ofaa477 BACKGROUND: People experiencing homelessness are at increased risk of coronavirus disease 2019 (COVID-19), but little is known about specific risk factors for infection within homeless shelters. METHODS: We performed widespread severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction testing and collected risk factor information at all homeless shelters in Chicago with at least 1 reported case of COVID-19 (n = 21). Multivariable, mixed-effects log-binomial models were built to estimate adjusted prevalence ratios (aPRs) for SARS-CoV-2 infection for both individual- and facility-level risk factors. RESULTS: During March 1 to May 1, 2020, 1717 shelter residents and staff were tested for SARS-CoV-2; 472 (27%) persons tested positive. Prevalence of infection was higher for residents (431 of 1435, 30%) than for staff (41 of 282, 15%) (prevalence ratio = 2.52; 95% confidence interval [CI], 1.78-3.58). The majority of residents with SARS-CoV-2 infection (293 of 406 with available information about symptoms, 72%) reported no symptoms at the time of specimen collection or within the following 2 weeks. Among residents, sharing a room with a large number of people was associated with increased likelihood of infection (aPR for sharing with >20 people compared with single rooms = 1.76; 95% CI, 1.11-2.80), and current smoking was associated with reduced likelihood of infection (aPR = 0.71; 95% CI, 0.60-0.85). At the facility level, a higher proportion of residents leaving and returning each day was associated with increased prevalence (aPR = 1.08; 95% CI, 1.01-1.16), whereas an increase in the number of private bathrooms was associated with reduced prevalence (aPR for 1 additional private bathroom per 100 people = 0.92; 95% CI, 0.87-0.98). CONCLUSIONS: We identified a high prevalence of SARS-CoV-2 infections in homeless shelters. Reducing the number of residents sharing dormitories might reduce the likelihood of SARS-CoV-2 infection. When community transmission is high, limiting movement of persons experiencing homelessness into and out of shelters might also be beneficial. |
The Seattle Flu Study: a multiarm community-based prospective study protocol for assessing influenza prevalence, transmission and genomic epidemiology.
Chu HY , Boeckh M , Englund JA , Famulare M , Lutz B , Nickerson DA , Rieder M , Starita LM , Adler A , Brandstetter E , Frazer CD , Han PD , Gulati RK , Hadfield J , Jackson M , Kiavand A , Kimball LE , Lacombe K , Newman K , Sibley TR , Logue JK , Lyon VR , Wolf CR , Zigman Suchsland M , Shendure J , Bedford T . BMJ Open 2020 10 (10) e037295 INTRODUCTION: Influenza epidemics and pandemics cause significant morbidity and mortality. An effective response to a potential pandemic requires the infrastructure to rapidly detect, characterise, and potentially contain new and emerging influenza strains at both an individual and population level. The objective of this study is to use data gathered simultaneously from community and hospital sites to develop a model of how influenza enters and spreads in a population. METHODS AND ANALYSIS: Starting in the 2018-2019 season, we have been enrolling individuals with acute respiratory illness from community sites throughout the Seattle metropolitan area, including clinics, childcare facilities, Seattle-Tacoma International Airport, workplaces, college campuses and homeless shelters. At these sites, we collect clinical data and mid-nasal swabs from individuals with at least two acute respiratory symptoms. Additionally, we collect residual nasal swabs and data from individuals who seek care for respiratory symptoms at four regional hospitals. Samples are tested using a multiplex molecular assay, and influenza whole genome sequencing is performed for samples with influenza detected. Geospatial mapping and computational modelling platforms are in development to characterise the regional spread of influenza and other respiratory pathogens. ETHICS AND DISSEMINATION: The study was approved by the University of Washington's Institutional Review Board (STUDY00006181). Results will be disseminated through talks at conferences, peer-reviewed publications and on the study website (www.seattleflu.org). |
Biomarkers of exposure among USA adult hookah users: Results from wave 1 of the Population Assessment of Tobacco and Health (PATH) Study (2013-2014)
Travers MJ , Rivard C , Sharma E , Retzky S , Yucesoy B , Goniewicz ML , Stanton CA , Chen J , Callahan-Lyon P , Kimmel HL , Xia B , Wang Y , Sosnoff CS , De Jesús VR , Blount BC , Hecht SS , Hyland A . Int J Environ Res Public Health 2020 17 (17) Hookah smoking has become common in the USA, especially among young adults. This study measured biomarkers of exposure to known tobacco product toxicants in a population-based sample of exclusive, established hookah users. Urinary biomarker data from 1753 adults in Wave 1 of the Population Assessment of Tobacco and Health (PATH) Study were used to compare geometric mean concentrations of biomarkers of exposure in exclusive, established past 30-day hookah users to never users of tobacco. Geometric mean ratios were calculated comparing hookah user groups with never users adjusting for age, sex, race/ethnicity, education, past 30-day marijuana use, secondhand smoke exposure and creatinine. Past 30-day hookah users (n = 98) had 10.6 times the urinary cotinine level of never tobacco users. Compared to never tobacco users, past 30-day hookah users had 2.3 times the level of the carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), 1.3 times higher polycyclic aromatic hydrocarbons (PAHs) 3-hydroxyfluorene and 1-hydroxypyrene, 1.8 times higher levels of acrylonitrile, 1.3 times higher levels of acrylamide, and 1.2 times higher levels of acrolein exposure. These data indicate that hookah use is a significant source of exposure to nicotine, carcinogens, and respiratory toxicants. |
Heart attacks, bloody noses, and other "emotional problems": Cultural and conceptual issues with the Spanish translation of self-report emotional health items
Flynn MA , Eggerth DE , Jacobson CJJr , Lyon SM . Fam Community Health 2020 44 (1) 1-9 This article examines how respondents understood items in the Spanish versions of the Short-Form 36 (SF-36v2). Cognitive interviews of the SF-36 were conducted in 2 phases with 46 Spanish speakers living in the United States. Roughly one-third (17/46) of respondents had difficulty understanding the Role Emotional items upon their initial reading, and almost half (21/46) provided examples that were inconsistent with the intended meaning of the items. The findings of this study underscore the importance of conducting cognitive testing to ensure conceptual equivalence of any instrument regardless of how well validated it appears to be. |
Transmission of eastern equine encephalitis virus from an organ donor to 3 transplant recipients
Pouch SM , Katugaha SB , Shieh WJ , Annambhotla P , Walker WL , Basavaraju SV , Jones J , Huynh T , Reagan-Steiner S , Bhatnagar J , Grimm K , Stramer SL , Gabel J , Lyon GM , Mehta AK , Kandiah P , Neujahr DC , Javidfar J , Subramanian RM , Parekh SM , Shah P , Cooper L , Psotka MA , Radcliffe R , Williams C , Zaki SR , Staples JE , Fischer M , Panella AJ , Lanciotti RS , Laven JJ , Kosoy O , Rabe IB , Gould CV . Clin Infect Dis 2019 69 (3) 450-458 BACKGROUND: In fall 2017, 3 solid organ transplant (SOT) recipients from a common donor developed encephalitis within 1 week of transplantation, prompting suspicion of transplant-transmitted infection. Eastern equine encephalitis virus (EEEV) infection was identified during testing of endomyocardial tissue from the heart recipient. METHODS: We reviewed medical records of the organ donor and transplant recipients and tested serum, whole blood, cerebrospinal fluid, and tissue from the donor and recipients for evidence of EEEV infection by multiple assays. We investigated blood transfusion as a possible source of organ donor infection by testing remaining components and serum specimens from blood donors. We reviewed data from the pretransplant organ donor evaluation and local EEEV surveillance. RESULTS: We found laboratory evidence of recent EEEV infection in all organ recipients and the common donor. Serum collected from the organ donor upon hospital admission tested negative, but subsequent samples obtained prior to organ recovery were positive for EEEV RNA. There was no evidence of EEEV infection among donors of the 8 blood products transfused into the organ donor or in products derived from these donations. Veterinary and mosquito surveillance showed recent EEEV activity in counties nearby the organ donor's county of residence. Neuroinvasive EEEV infection directly contributed to the death of 1 organ recipient and likely contributed to death in another. CONCLUSIONS: Our investigation demonstrated EEEV transmission through SOT. Mosquito-borne transmission of EEEV to the organ donor was the likely source of infection. Clinicians should be aware of EEEV as a cause of transplant-associated encephalitis. |
Bioaerosol sampling of a ventilated patient with COVID-19.
Lane MA , Brownsword EA , Morgan JS , Babiker A , Vanairsdale SA , Lyon GM , Mehta AK , Ingersoll JM , Lindsley WG , Kraft CS . Am J Infect Control 2020 48 (12) 1540-1542 Bioaerosol samples were collected in an airborne infection isolation room, bathroom and anteroom of a ventilated patient with coronavirus disease 2019. Twenty-eight samples were negative for SARS-CoV-2 nucleic acid, possibly due to the patient being on a closed-circuit ventilator or the efficiency of the air exchanges in the room. |
Use of personal care products during pregnancy in relation to urinary concentrations of select phenols: A longitudinal analysis from the SEPAGES feasibility study
Nakiwala D , Vernet C , Lyon-Caen S , Lavorel A , Rolland M , Cracowski C , Pin I , Calafat AM , Slama R , Philippat C . Int J Hyg Environ Health 2020 227 113518 BACKGROUND: Exposure to certain synthetic phenols is of growing concern, in particular among pregnant women, because of their endocrine disrupting nature. Many phenols are still authorized in personal care products (PCP). We aimed to assess if use of PCPs, by pregnant women could influence their urinary concentrations of synthetic phenols. METHODS: We used a panel design with intense urine sample collection. Eight women completed a diary with exact time and use of PCPs in three weeks. We measured the concentrations of phenols (four parabens, bisphenol A and S, two dichlorophenols, triclosan, and benzophenone-3) in 178 urine samples, collected during 7 consecutive days at 3 time points during pregnancy. We characterized PCP use as the total number of PCP applications or as a single PCP use (yes/no) in three time windows (0-6, 6 to 12 and 12 to 24h before each urine sample collection). We used adjusted linear and Tobit regressions to assess associations between PCP use and phenol urinary concentrations. RESULTS: The total number of PCP applications was positively associated with ethylparaben, propylparaben and butylparaben concentrations. We observed a peak in urinary concentration of ethylparaben, butylparaben and propylparaben at 2.86, 2.55 and 2.67h since last PCP use, respectively and twelve different types of PCPs were positively associated with at least one of these parabens. The bisphenol S concentration increased by 12.4% (95%CI: confidence interval: 5.9; 19.3) for each additional PCP application in the 12 to 24 time window and use of specific PCPs such as anti-stretchmarks cream, facial cleanser and shower gel. Associations varied by time window. CONCLUSION: Our study showed that PCP use was associated with a short-term increase in the urinary concentration of ethylparaben, butylparaben and propylparaben, but not methylparaben. This study also reported a positive association between the use of PCPs and the bisphenol S concentration, a finding that warrants further investigation in cohorts with repeated collection of urine samples and detailed information on PCP use. |
Acrophialophora levis brain abscess in a kidney transplant patient: A case report and review of the literature
Modlin CE , Collins LF , Burd EM , Lockhart SR , Marshall Lyon G . Med Mycol Case Rep 2020 28 12-15 We report the first case of Acrophialophora levis causing cerebral phaeohyphomycosis in a solid organ transplantation recipient. A. levis is a rare cause of invasive dematiaceous fungal infection among immunocompromised persons. We describe the clinical course of a kidney transplant patient who presented with acute hemiplegia due to a brain abscess from which A. levis was isolated. We review published clinical cases attributed to Acrophialophora species infection and discuss current limitations in its identification, diagnosis and management. |
An empirical validation of the within-subject biospecimens pooling approach to minimize exposure misclassification in biomarker-based studies
Vernet C , Philippat C , Agier L , Calafat AM , Ye X , Lyon-Caen S , Hainaut P , Siroux V , Schisterman EF , Slama R . Epidemiology 2019 30 (5) 756-767 BACKGROUND: Within-subject biospecimens pooling can theoretically reduce bias in dose-response functions from biomarker-based studies when exposure assessment suffers from classical-type error. However, collecting many urine voids each day is cumbersome. We evaluated the empirical validity of a within-subject pooling approach and compared several options to avoid sampling each void. METHODS: In 16 pregnant women who collected a spot of each urine void over several nonconsecutive weeks, we compared concentrations of 10 phenols in daily, weekly, and pregnancy within-subject pools. We pooled either three or all daily samples. In a simulation study using these data, we quantified bias in dose-response functions when using one to 20 urine samples per subject to assess methylparaben (a compound with moderate within-subject variability) and bisphenol A (high variability) exposures. RESULTS: Correlations between exposure estimates from pools of all and of only three voids per day were above 0.80 for all time windows and compounds, except for benzophenone-3 and triclosan in the daily time window (correlations, 0.57-0.68). With one spot sample to assess pregnancy exposure, correlations were all below 0.74. Using only one biospecimen led to attenuation bias in the dose-response functions of 29% (methylparaben) and 69% (bisphenol A); four samples for methylparaben and 18 for bisphenol A decreased bias to 10%. CONCLUSIONS: For nonpersistent chemicals, collecting and pooling three samples per day instead of all daily samples efficiently estimates exposures over a week or more. Collecting around 20 biospecimens can strongly limit attenuation bias for nonpersistent chemicals such as bisphenol A. |
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. |
Macrophage activation marker soluble CD163 associated with fatal and severe Ebola virus disease in humans
McElroy AK , Shrivastava-Ranjan P , Harmon JR , Martines RB , Silva-Flannery L , Flietstra TD , Kraft CS , Mehta AK , Lyon GM , Varkey JB , Ribner BS , Nichol ST , Zaki SR , Spiropoulou CF . Emerg Infect Dis 2019 25 (2) 290-298 Ebola virus disease (EVD) is associated with elevated cytokine levels, and hypercytokinemia is more pronounced in fatal cases. This type of hyperinflammatory state is reminiscent of 2 rheumatologic disorders known as macrophage activation syndrome and hemophagocytic lymphohistiocytosis, which are characterized by macrophage and T-cell activation. An evaluation of 2 cohorts of patients with EVD revealed that a marker of macrophage activation (sCD163) but not T-cell activation (sCD25) was associated with severe and fatal EVD. Furthermore, substantial immunoreactivity of host tissues to a CD163-specific antibody, predominantly in areas of extensive immunostaining for Ebola virus antigens, was observed in fatal cases. These data suggest that host macrophage activation contributes to EVD pathogenesis and that directed antiinflammatory therapies could be beneficial in the treatment of EVD. |
Within-day, between-day, and between-week variability of urinary concentrations of phenol biomarkers in pregnant women
Vernet C , Philippat C , Calafat AM , Ye X , Lyon-Caen S , Siroux V , Schisterman EF , Slama R . Environ Health Perspect 2018 126 (3) 037005 BACKGROUND: Toxicology studies have shown adverse effects of developmental exposure to industrial phenols. Evaluation in humans is challenged by potentially marked within-subject variability of phenol biomarkers in pregnant women, which is poorly characterized. OBJECTIVES: We aimed to characterize within-day, between-day, and between-week variability of phenol urinary biomarker concentrations during pregnancy. METHODS: In eight French pregnant women, we collected all urine voids over a 1-wk period (average, 60 samples per week per woman) at three occasions (15+/-2, 24+/-2, and 32+/-1 gestational weeks) in 2012-2013. Aliquots of each day and of the whole week were pooled within-subject. We assayed concentrations of 10 phenols in these pools, and, for two women, in all spot (unpooled) samples collected during a 1-wk period. We characterized variability using intraclass correlation coefficients (ICCs) with spot samples (within-day variability), daily pools (between-day variability), and weekly pools (between-week variability). RESULTS: For most biomarkers, the within-day variability was high (ICCs between 0.03 and 0.50). The between-day variability, based on samples pooled within each day, was much lower, with ICCs >0.60 except for bisphenol S (0.14, 95% confidence interval [CI]: 0.00, 0.39). The between-week variability differed between compounds, with triclosan and bisphenol S having the lowest ICCs (<0.3) and 2,5-dichlorophenol the highest (ICC >0.9). CONCLUSION: During pregnancy, phenol biomarkers showed a strong within-day variability, while the variability between days of a given week was more limited. One biospecimen is not enough to efficiently characterize exposure; collecting biospecimens during a single week may be enough to represent well the whole pregnancy exposure for some but not all phenols. |
Favipiravir and ribavirin treatment of epidemiologically linked cases of Lassa fever
Raabe VN , Kann G , Ribner BS , Morales A , Varkey JB , Mehta AK , Lyon GM , Vanairsdale S , Faber K , Becker S , Eickmann M , Strecker T , Brown S , Patel K , De Leuw P , Schuettfort G , Stephan C , Rabenau H , Klena JD , Rollin PE , McElroy A , Stroher U , Nichol S , Kraft CS , Wolf T . Clin Infect Dis 2017 65 (5) 855-859 Two patients with Lassa fever are described who are the first human cases treated with a combination of ribavirin and favipiravir. Both patients survived but developed transaminitis and had prolonged detectable virus RNA in blood and semen, suggesting that the possibility of sexual transmission of Lassa virus should be considered. |
A case of human Lassa virus infection with robust acute T-cell activation and long-term virus-specific T-cell responses
McElroy AK , Akondy RS , Harmon JR , Ellebedy AH , Cannon D , Klena JD , Sidney J , Sette A , Mehta AK , Kraft CS , Lyon MG , Varkey JB , Ribner BS , Nichol ST , Spiropoulou CF . J Infect Dis 2017 215 (12) 1862-1872 A nurse who acquired Lassa virus infection in Togo in the spring of 2016 was repatriated to the United States for care at Emory University Hospital. Serial sampling from this patient permitted the characterization of several aspects of the innate and cellular immune responses to Lassa virus. Although most of the immune responses correlated with the kinetics of viremia resolution, the CD8 T-cell response was of surprisingly high magnitude and prolonged duration, implying prolonged presentation of viral antigens. Indeed, long after viremia resolution, there was persistent viral RNA detected in the semen of the patient, accompanied by epididymitis, suggesting the male reproductive tract as 1 site of antigen persistence. Consistent with the magnitude of acute T-cell responses, the patient ultimately developed long-term, polyfunctional memory T-cell responses to Lassa virus. |
The epidemiology and outcomes of invasive Candida infections among organ transplant recipients in the United States: Results of the Transplant-Associated Infection Surveillance Network (TRANSNET)
Andes DR , Safdar N , Baddley JW , Alexander B , Brumble L , Freifeld A , Hadley S , Herwaldt L , Kauffman C , Lyon GM , Morrison V , Patterson T , Perl T , Walker R , Hess T , Chiller T , Pappas PG . Transpl Infect Dis 2016 18 (6) 921-931 BACKGROUND: Invasive candidiasis (IC) is a common cause of mortality in solid organ transplant recipients (OTRs), but knowledge of epidemiology in this population is limited. METHOD: The present analysis describes data from 15 US centers that prospectively identified IC from nearly 17,000 OTRs. Analyses were undertaken to determine predictors of infection and mortality. RESULTS: A total of 639 cases of IC were identified. The most common species was Candida albicans (46.3%), followed by Candida glabrata (24.4%) and Candida parapsilosis (8.1%). In 68 cases >1 species was identified. The most common infection site was bloodstream (44%), followed by intra-abdominal (14%). The most frequently affected allograft groups were liver (41.1%) and kidney (35.3%). All-cause mortality at 90 days was 26.5% for all species and was highest for Candida tropicalis (44%) and C. parapsilosis (35.2%). Non-white race and female gender were more commonly associated with non-albicans species. A high rate of breakthrough IC was seen in patients receiving antifungal prophylaxis (39%). Factors associated with mortality include organ dysfunction, lung transplant, and treatment with a polyene antifungal. The only modifiable factor identified was choice of antifungal drug class based upon infecting Candida species. CONCLUSION: These data highlight the common and distinct features of IC in OTRs. This article is protected by copyright. All rights reserved. |
Long-term management of panuveitis and iris heterochromia in an Ebola survivor
Shantha JG , Crozier I , Varkey JB , Kraft CS , Lyon GM 3rd , Mehta AK , Carlson RD , Hill CE , Kumar G , Debiec MR , Patel PS , Olsen TW , Nussenblatt RB , Martin DF , Stroher U , Uyeki TM , Ribner BS , Smith JR , Yeh S . Ophthalmology 2016 123 (12) 2626-2628 e2 The 2013-2016 West African Ebola virus disease (EVD) outbreak has been the largest in history with 28,616 cases and 11,310 deaths in the highest transmission countries of Sierra Leone, Guinea, and Liberia.1 Reports of uveitis have emerged in EVD survivors.2-3 Herein we discuss clinical features, multimodality imaging, and long-term management of aggressive, sight-threatening panuveitis, in an EVD survivor, providing insight into the pathogenesis of this condition. |
Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination
Ellebedy AH , Jackson KJ , Kissick HT , Nakaya HI , Davis CW , Roskin KM , McElroy AK , Oshansky CM , Elbein R , Thomas S , Lyon GM , Spiropoulou CF , Mehta AK , Thomas PG , Boyd SD , Ahmed R . Nat Immunol 2016 17 (10) 1226-34 Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody. |
Ebola virus disease and critical illness
Leligdowicz A , Fischer WA 2nd , Uyeki TM , Fletcher TE , Adhikari NK , Portella G , Lamontagne F , Clement C , Jacob ST , Rubinson L , Vanderschuren A , Hajek J , Murthy S , Ferri M , Crozier I , Ibrahima E , Lamah MC , Schieffelin JS , Brett-Major D , Bausch DG , Shindo N , Chan AK , O'Dempsey T , Mishra S , Jacobs M , Dickson S , Lyon GM 3rd , Fowler RA . Crit Care 2016 20 (1) 217 As of 20 May 2016 there have been 28,646 cases and 11,323 deaths resulting from the West African Ebola virus disease (EVD) outbreak reported to the World Health Organization. There continue to be sporadic flare-ups of EVD cases in West Africa.EVD presentation is nonspecific and characterized initially by onset of fatigue, myalgias, arthralgias, headache, and fever; this is followed several days later by anorexia, nausea, vomiting, diarrhea, and abdominal pain. Anorexia and gastrointestinal losses lead to dehydration, electrolyte abnormalities, and metabolic acidosis, and, in some patients, acute kidney injury. Hypoxia and ventilation failure occurs most often with severe illness and may be exacerbated by substantial fluid requirements for intravascular volume repletion and some degree of systemic capillary leak. Although minor bleeding manifestations are common, hypovolemic and septic shock complicated by multisystem organ dysfunction appear the most frequent causes of death.Males and females have been equally affected, with children (0-14 years of age) accounting for 19 %, young adults (15-44 years) 58 %, and older adults (≥45 years) 23 % of reported cases. While the current case fatality proportion in West Africa is approximately 40 %, it has varied substantially over time (highest near the outbreak onset) according to available resources (40-90 % mortality in West Africa compared to under 20 % in Western Europe and the USA), by age (near universal among neonates and high among older adults), and by Ebola viral load at admission.While there is no Ebola virus-specific therapy proven to be effective in clinical trials, mortality has been dramatically lower among EVD patients managed with supportive intensive care in highly resourced settings, allowing for the avoidance of hypovolemia, correction of electrolyte and metabolic abnormalities, and the provision of oxygen, ventilation, vasopressors, and dialysis when indicated. This experience emphasizes that, in addition to evaluating specific medical treatments, improving the global capacity to provide supportive critical care to patients with EVD may be the greatest opportunity to improve patient outcomes. |
Kinetic analysis of biomarkers in a cohort of US patients with Ebola virus disease
McElroy AK , Harmon JR , Flietstra TD , Campbell S , Mehta AK , Kraft CS , Lyon MG , Varkey JB , Ribner BS , Kratochvil CJ , Iwen PC , Smith PW , Ahmed R , Nichol ST , Spiropoulou CF . Clin Infect Dis 2016 63 (4) 460-7 BACKGROUND: Ebola virus (EBOV) infection causes a severe and often fatal disease. Despite the fact that more than 30 000 individuals have acquired Ebola virus disease (EVD), the medical and scientific community still does not have a clear understanding of the mechanisms by which EBOV causes such severe disease. METHODS: In this study, 54 biomarkers in plasma samples serially collected from 7 patients with EVD were analyzed in an attempt to define the kinetics of inflammatory modulators. Two clinical disease groups were defined (moderate and severe) based on the need for clinical support. Biomarkers were evaluated for correlation with viremia and clinical disease in an effort to identify pathways that could be useful targets of therapeutic intervention. RESULTS: Patients with severe disease had higher viremia than those with moderate disease. Several biomarkers of immune activation and control were significantly elevated in patients with moderate disease. A series of pro-inflammatory cytokines and chemokines were significantly elevated in patients with severe disease. CONCLUSIONS: Biomarkers that were associated with severe EVD were proinflammatory and indicative of endothelial or coagulation cascade dysfunction, as has been seen historically in patients with fatal outcomes. In contrast, biomarkers that were associated with moderate EVD were suggestive of a strong interferon response and control of both innate and adaptive responses. Therefore, clinical interventions that modulate the phenotype and magnitude of immune activation may be beneficial in treating EVD. |
An oil-in-water nanoemulsion enhances immunogenicity of H5N1 vaccine in mice
Cao W , Davis WG , Kim JH , De La Cruz JA , Taylor A , Hendrickson GR , Kumar A , Ranjan P , Lyon LA , Katz JM , Gangappa S , Sambhara S . Nanomedicine 2016 12 (7) 1909-1917 To enhance the immunogenicity of the Influenza H5N1 vaccine, we developed an oil-in-water nanoemulsion (NE) adjuvant. NE displayed good temperature stability and maintained particle size. More importantly, it significantly enhanced IL-6 and MCP-1 production to recruit innate cells, including neutrophils, monocytes/macrophages and dendritic cells to the local environment. Furthermore, NE enhanced dendritic cell function to induce robust antigen-specific T and B cell immune responses. NE-adjuvanted H5N1 vaccine not only elicited significantly higher and long-lasting antibody responses, but also conferred enhanced protection against homologous clade 1 as well as heterologous clade 2 H5N1 virus challenge in young as well as in aged mice. The pre-existing immunity to seasonal influenza did not affect the immunogenicity of NE-adjuvanted H5N1 vaccine. |
Ebola virus persistence in semen of male survivors
Uyeki TM , Erickson BR , Brown S , McElroy AK , Cannon D , Gibbons A , Sealy T , Kainulainen MH , Schuh AJ , Kraft CS , Mehta AK , Lyon GM , Varkey JB , Ribner BS , Ellison RT 3rd , Carmody E , Nau GJ , Spiropoulou C , Nichol ST , Stroher U . Clin Infect Dis 2016 62 (12) 1552-1555 We investigated the duration of Ebola virus (EBOV) ribonucleic acid (RNA) and infectious EBOV in semen specimens of five Ebola virus disease (EVD) survivors. EBOV RNA and infectious EBOV was detected by real-time RT-PCR and virus culture out to 290 days and 70 days, respectively after EVD onset. |
Phaeohyphomycosis in transplant recipients: results from the Transplant Associated Infection Surveillance Network (TRANSNET)
McCarty TP , Baddley JW , Walsh TJ , Alexander BD , Kontoyiannis DP , Perl TM , Walker R , Patterson TF , Schuster MG , Lyon GM , Wingard JR , Andes DR , Park BJ , Brandt ME , Pappas PG . Med Mycol 2015 53 (5) 440-6 Transplant recipients are at a high risk for developing invasive fungal infections. The agents of phaeohyphomycosis are environmental molds found worldwide, and they cause a broad spectrum of disease including skin and subcutaneous lesions, pneumonia, central nervous system disease, fungemia, and disseminated disease. Using data from the Transplant Associated Infection Surveillance Network (TRANSNET), we evaluated patients with proven and probable phaeohyphomycosis. Centers collected data on demographics, co-morbid conditions, clinical features, treatment, and three-month mortality. Fifty-six patients with phaeohyphomycosis were identified from 15 centers, comprising 26 stem cell transplant (SCT) and 30 solid organ transplant (SOT) recipients. Median time to diagnosis post-transplant was 358 days (SCT 100 days; SOT 685 days; P = <.001). The most frequent pathogen was Alternaria species (32%). Disseminated disease was found in 55.4%. Cutaneous infection was more common in SOT (53.3% vs 23.1%; P = .021), while pulmonary disease was more common in SCT (57.7 vs. 26.7; P = .019). Voriconazole (44.6%) and amphotericin B preparations (37.5%) were the most common antifungal therapies. Overall mortality was 25% and was higher in SCT than in SOT (42% vs 10%; P = <.001). A wide variety of organisms encompass phaeohyphomycosis contributing to varying types of infection in transplant recipients. Site of infection, time to disease, and mortality varies significantly between SCT and SOT recipients. Lipid formulations of amphotericin B and voriconazole were the most common antifungals used to treat this disorder. |
Characteristics and clinical management of a cluster of 3 patients with Ebola virus disease, including the first domestically acquired cases in the United States
Liddell AM , Davey RT Jr , Mehta AK , Varkey JB , Kraft CS , Tseggay GK , Badidi O , Faust AC , Brown KV , Suffredini AF , Barrett K , Wolcott MJ , Marconi VC , Lyon GM 3rd , Weinstein GL , Weinmeister K , Sutton S , Hazbun M , Albarino CG , Reed Z , Cannon D , Stroher U , Feldman M , Ribner BS , Lane HC , Fauci AS , Uyeki TM . Ann Intern Med 2015 163 (2) 81-90 BACKGROUND: More than 26 000 cases of Ebola virus disease (EVD) have been reported in western Africa, with high mortality. Several patients have been medically evacuated to hospitals in the United States and Europe. Detailed clinical data are limited on the clinical course and management of patients with EVD outside western Africa. OBJECTIVE: To describe the clinical characteristics and management of a cluster of patients with EVD, including the first cases of Ebola virus (EBOV) infection acquired in the United States. DESIGN: Retrospective clinical case series. SETTING: Three U.S. hospitals in September and October 2014. PATIENTS: First imported EVD case identified in the United States and 2 secondary EVD cases acquired in the United States in critical care nurses who cared for the index case patient. MEASUREMENTS: Clinical recovery, EBOV RNA level, resolution of Ebola viremia, survival with discharge from hospital, or death. RESULTS: The index patient had high EBOV RNA levels, developed respiratory and renal failure requiring critical care support, and died. Both patients with secondary EBOV infection had nonspecific signs and symptoms and developed moderate illness; EBOV RNA levels were moderate, and both patients recovered. LIMITATION: Both surviving patients received uncontrolled treatment with multiple investigational agents, including convalescent plasma, which limits generalizability of the results. CONCLUSION: Early diagnosis, prompt initiation of supportive medical care, and moderate clinical illness likely contributed to successful outcomes in both survivors. The inability to determine the potential benefit of investigational therapies and the effect of patient-specific factors that may have contributed to less severe illness highlight the need for controlled clinical studies of these interventions, especially in the setting of a high level of supportive medical care. PRIMARY FUNDING SOURCE: None. |
Comparison of FilmArray® and qRT-PCR for the detection of Zaire ebolavirus from contrived and clinical specimens.
Southern TR , Racsa LD , Albarino CG , Fey PD , Hinrichs SH , Murphy CN , Herrera VL , Sambol AR , Hill CE , Ryan EL , Kraft CS , Campbell S , Sealy TK , Schuh A , Ritchie JC , Lyon GM 3rd , Mehta AK , Varkey JB , Ribner BS , Brantly KP , Stroher U , Iwen PC , Burd EM . J Clin Microbiol 2015 53 (9) 2956-60 Rapid, reliable and easy to use diagnostic assays for detection of Zaire ebolavirus (ZEBOV) are urgently needed. The goal of this study was to examine the percentage agreement among Emergency Use Authorization (EUA) tests for the detection of ZEBOV nucleic acid including the BioFire FilmArray(R) BioThreat (BT) panel, the FilmArray BT E-panel and the NP2 and VP40 quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) assays from the Centers for Disease Control and Prevention (CDC). Specimens used in this study included whole blood spiked with inactivated ZEBOV at known titers and whole blood, plasma and urine clinical specimens from persons diagnosed with Ebola virus disease (EVD). The percentage agreement for FilmArray and qRT-PCR assays using contrived whole blood specimens was 100% (6/6) for each ZEBOV dilution from 4x107-4x102 virus/ml as well as the no-virus negative control. The limit of detection for FilmArray and qRT-PCR based on duplicate positive results was determined to be 4x102 inactivated ZEBOV/ml. Percentage agreement between FilmArray and qRT-PCR using clinical specimens from patients with EVD was 85% (23/27) when testing whole blood, 90%(18/20) when testing whole blood by FilmArray and matched plasma by qRT-PCR and 85% (11/13) when testing urine. Of 60 specimens, eight discordant results were noted with ZEBOV nucleic acid detected only by FilmArray in four specimens and only by qRT-PCR in the remaining four. These findings demonstrate that the rapid and easy to use FilmArray panels are effective tests for evaluating patients with EVD. |
Serological correlates of protection against a GII.4 norovirus
Atmar RL , Bernstein DI , Lyon GM , Treanor JJ , Al-Ibrahim MS , Graham DY , Vinje J , Jiang X , Gregoricus N , Frenck RW , Moe CL , Chen WH , Ferreira J , Barrett J , Opekun AR , Estes MK , Borkowski A , Baehner F , Goodwin R , Edmonds A , Mendelman PM . Clin Vaccine Immunol 2015 22 (8) 923-9 Noroviruses are the leading cause of acute gastroenteritis worldwide, and norovirus vaccine prevention strategies are under evaluation. The immunogenicity of two doses of bivalent GI.1/GII.4 (50mug VLP of each strain adjuvanted with aluminum hydroxide and MPL) norovirus vaccine administered to healthy adults in a phase 1-2 double-blind, placebo-controlled trial was determined using virus-specific, serum total antibody ELISA, IgG, IgA and histoblood group antigen (HBGA) blocking assays. Trial participants subsequently received an oral live virus challenge with a GII.4 strain and vaccine efficacy results have been reported previously (D.I. Bernstein et al. J Infect Dis 211:870-878, 2015, doi:10.1093/infdis/jiu497). This report assesses the impact of pre-challenge serum antibody levels on infection and illness outcomes. Serum antibody responses were observed in vaccine recipients by all antibody assays, with first dose seroresponse frequencies ranging from 88-100% for the GI.1 antigen and from 69-84% for the GII.4 antigen. There was little increase in antibody level after the second vaccine dose. Among placebo subjects, higher pre-challenge serum anti-GII.4 HBGA-blocking and IgA antibody levels, but not IgG or total antibody levels, were associated with a lower frequency of virus infection and associated illness. Notably, some placebo subjects without measurable serum antibody pre-challenge did not become infected after norovirus challenge. In vaccinees, anti-GII.4 HBGA-blocking antibody levels >1:500 were associated with a lower frequency of moderate-to-severe vomiting or diarrheal illness. In this study, pre-challenge serum HBGA antibody titers correlated with protection in placebo subjects; however, other factors may impact the likelihood of infection and illness after virus exposure. |
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