Last data update: Apr 22, 2024. (Total: 46599 publications since 2009)
Records 1-30 (of 134 Records) |
Query Trace: Dean A [original query] |
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Clinical and laboratory findings of the first imported case of Middle East respiratory syndrome coronavirus to the United States.
Kapoor M , Pringle K , Kumar A , Dearth S , Liu L , Lovchik J , Perez O , Pontones P , Richards S , Yeadon-Fagbohun J , Breakwell L , Chea N , Cohen NJ , Schneider E , Erdman D , Haynes L , Pallansch M , Tao Y , Tong S , Gerber S , Swerdlow D , Feikin DR . Clin Infect Dis 2014 59 (11) 1511-8 BACKGROUND: The Middle East respiratory syndrome coronavirus (MERS-CoV) was discovered September 2012 in the Kingdom of Saudi Arabia (KSA). The first US case of MERS-CoV was confirmed on 2 May 2014. METHODS: We summarize the clinical symptoms and signs, laboratory and radiologic findings, and MERS-CoV-specific tests. RESULTS: The patient is a 65-year-old physician who worked in a hospital in KSA where MERS-CoV patients were treated. His illness onset included malaise, myalgias, and low-grade fever. He flew to the United States on day of illness (DOI) 7. His first respiratory symptom, a dry cough, developed on DOI 10. On DOI 11, he presented to an Indiana hospital as dyspneic, hypoxic, and with a right lower lobe infiltrate on chest radiography. On DOI 12, his serum tested positive by real-time reverse transcription polymerase chain reaction (rRT-PCR) for MERS-CoV and showed high MERS-CoV antibody titers, whereas his nasopharyngeal swab was rRT-PCR negative. Expectorated sputum was rRT-PCR positive the following day, with a high viral load (5.31 × 10(6) copies/mL). He was treated with antibiotics, intravenous immunoglobulin, and oxygen by nasal cannula. He was discharged on DOI 22. The genome sequence was similar (>99%) to other known MERS-CoV sequences, clustering with those from KSA from June to July 2013. CONCLUSIONS: This patient had a prolonged nonspecific prodromal illness before developing respiratory symptoms. Both sera and sputum were rRT-PCR positive when nasopharyngeal specimens were negative. US clinicians must be vigilant for MERS-CoV in patients with febrile and/or respiratory illness with recent travel to the Arabian Peninsula, especially among healthcare workers. |
Performance of a tic screening tool (MOVeIT) in comparison to expert clinician assessment in a developmental-behavioral pediatrics clinic sample
Vermilion JA , Bitsko RH , Danielson ML , Bonifacio KP , Dean SL , Hyman SL , Augustine EF , Mink JW , Morrison PE , Vierhile AE , Sulkes SB , van Wijngaarden E , Adams HR . Evid Based Pract Child Adolesc Ment Health 2023 Youth with intellectual and developmental disabilities typically have higher rates of tics and stereotypies compared to children with otherwise typical development. Differentiating between these two pediatric movement disorders can be challenging due to overlapping clinical features, but is relevant due to distinct treatment modalities. The current study evaluated sensitivity and specificity of a tic screening measure, the Motor or Vocal Inventory of Tics (MOVeIT) in a pediatric sample enriched for stereotypy and tics. Children (n = 199, age 2–15 years old) receiving care in a developmental-behavioral pediatrics clinic underwent a gold-standard diagnostic assessment by a tic expert; these evaluations were compared to the MOVeIT. The MOVeIT demonstrated good sensitivity (89.8%) and relatively lower specificity (57.1%) compared to tic expert for detecting tics in the overall sample. Specificity of the MOVeIT to identify tics improved to 75% when excluding children with co-occurring stereotypy. For children with tics and co-occurring stereotypy, sensitivity remained high (91.9%) but specificity was low (39.1%). The area under the curve (AUC) value to detect tics on the MOVeIT compared to the tic expert gold standard was significantly higher for children without stereotypy (AUC = 85.7%) than those with stereotypy (AUC = 64.3%, p <.01). Overall, the ability to detect tics was better in those without co-occurring stereotypy symptoms. Further work is needed to establish the utility of the MOVeIT in populations where there is a high likelihood of co-occurring tics and stereotypy and in general population settings. Accurate distinction between tics and stereotypy will guide choices for intervention and anticipatory guidance for families. © 2023 Society of Clinical Child & Adolescent Psychology. |
Transmission of yellow fever vaccine virus through blood transfusion and organ transplantation in the USA in 2021: Report of an investigation
Gould CV , Free RJ , Bhatnagar J , Soto RA , Royer TL , Maley WR , Moss S , Berk MA , Craig-Shapiro R , Kodiyanplakkal RPL , Westblade LF , Muthukumar T , Puius YA , Raina A , Hadi A , Gyure KA , Trief D , Pereira M , Kuehnert MJ , Ballen V , Kessler DA , Dailey K , Omura C , Doan T , Miller S , Wilson MR , Lehman JA , Ritter JM , Lee E , Silva-Flannery L , Reagan-Steiner S , Velez JO , Laven JJ , Fitzpatrick KA , Panella A , Davis EH , Hughes HR , Brault AC , St George K , Dean AB , Ackelsberg J , Basavaraju SV , Chiu CY , Staples JE . Lancet Microbe 2023 4 (9) e711-e721 BACKGROUND: In 2021, four patients who had received solid organ transplants in the USA developed encephalitis beginning 2-6 weeks after transplantation from a common organ donor. We describe an investigation into the cause of encephalitis in these patients. METHODS: From Nov 7, 2021, to Feb 24, 2022, we conducted a public health investigation involving 15 agencies and medical centres in the USA. We tested various specimens (blood, cerebrospinal fluid, intraocular fluid, serum, and tissues) from the organ donor and recipients by serology, RT-PCR, immunohistochemistry, metagenomic next-generation sequencing, and host gene expression, and conducted a traceback of blood transfusions received by the organ donor. FINDINGS: We identified one read from yellow fever virus in cerebrospinal fluid from the recipient of a kidney using metagenomic next-generation sequencing. Recent infection with yellow fever virus was confirmed in all four organ recipients by identification of yellow fever virus RNA consistent with the 17D vaccine strain in brain tissue from one recipient and seroconversion after transplantation in three recipients. Two patients recovered and two patients had no neurological recovery and died. 3 days before organ procurement, the organ donor received a blood transfusion from a donor who had received a yellow fever vaccine 6 days before blood donation. INTERPRETATION: This investigation substantiates the use of metagenomic next-generation sequencing for the broad-based detection of rare or unexpected pathogens. Health-care workers providing vaccinations should inform patients of the need to defer blood donation for at least 2 weeks after receiving a yellow fever vaccine. Despite mitigation strategies and safety interventions, a low risk of transfusion-transmitted infections remains. FUNDING: US Centers for Disease Control and Prevention (CDC), the Biomedical Advanced Research and Development Authority, and the CDC Epidemiology and Laboratory Capacity Cooperative Agreement for Infectious Diseases. |
Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabs (preprint)
Bowden KE , Joseph SJ , Cartee JC , Ziklo N , Danavall D , Raphael BH , Read TD , Dean D . bioRxiv 2020 2020.09.04.282459 Chlamydia trachomatis is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. U.S. cases have been steadily increasing for more than a decade in both the urogenital tract and rectum. C. trachomatis is an obligate intracellular bacterium that is not easily cultured, limiting the capacity for genome studies to understand strain diversity and emergence among various patient populations globally. While Agilent SureSelectXT target-enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival and rectal samples, efficiencies are only 60-80% for ≥95-100% genome coverage. We therefore re-designed and expanded the RNA bait library to augment enrichment of the organism from clinical samples to improve efficiency. We describe the expanded library, the limit of detection for C. trachomatis genome copy input, and the 100% efficiency and high-resolution of generated genomes where genomic recombination among paired vaginal and rectal specimens from four patients was identified. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, among geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.Importance Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, and there is limited information on rectal C. trachomatis transmission and its impact on morbidity. To improve efficiency of previous studies involving whole genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we expanded the RNA bait library to augment enrichment of the organism from clinical samples. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis. We show the new system is sensitive for near identical genomes of C. trachomatis from two body sites in four women. Further, we provide a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital and rectal infections, and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity.Competing Interest StatementThe authors have declared no competing interest. |
Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines (preprint)
Lewnard JA , Patel MM , Jewell NP , Verani JR , Kobayashi M , Tenforde MW , Dean NE , Cowling BJ , Lopman BA . medRxiv 2021 2021.01.21.21250258 Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. These are now in planning amid the ongoing rollout of SARS-CoV-2 vaccines globally. While traditional case-control (TCC) and test-negative design (TND) studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here we review the theoretical basis for estimation of vaccine direct effects under TCC and TND frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, non-specific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The TCC may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The TND reduces but may not eliminate this confounding, for instance if individuals who receive vaccination seek care or testing for less-severe infection. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages.Competing Interest StatementJAL has received grants and consulting fees from Pfizer, Inc. unrelated to this research.Funding StatementThis work was supported by grants R01-AI14812701 from the National Institute for Allergy and Infectious Diseases to NPJ and JAL, and R01-AI139761 from the National Institute for Allergy and Infectious Diseases to NED.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:N/AAll 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.YesThis is a theoretical study without patient data; equations used to generate the figures appear in the manuscript. |
The United States COVID-19 Forecast Hub dataset (preprint)
Cramer EY , Huang Y , Wang Y , Ray EL , Cornell M , Bracher J , Brennen A , Rivadeneira AJC , Gerding A , House K , Jayawardena D , Kanji AH , Khandelwal A , Le K , Mody V , Mody V , Niemi J , Stark A , Shah A , Wattanchit N , Zorn MW , Reich NG , US COVID-19 Forecast Hub Consortium , Lopez VK , Walker JW , Slayton RB , Johansson MA , Biggerstaff M . medRxiv 2021 2021.11.04.21265886 Academic researchers, government agencies, industry groups, and individuals have produced forecasts at an unprecedented scale during the COVID-19 pandemic. To leverage these forecasts, the United States Centers for Disease Control and Prevention (CDC) partnered with an academic research lab at the University of Massachusetts Amherst to create the US COVID-19 Forecast Hub. Launched in April 2020, the Forecast Hub is a dataset with point and probabilistic forecasts of incident hospitalizations, incident cases, incident deaths, and cumulative deaths due to COVID-19 at national, state, and county levels in the United States. Included forecasts represent a variety of modeling approaches, data sources, and assumptions regarding the spread of COVID-19. The goal of this dataset is to establish a standardized and comparable set of short-term forecasts from modeling teams. These data can be used to develop ensemble models, communicate forecasts to the public, create visualizations, compare models, and inform policies regarding COVID-19 mitigation. These open-source data are available via download from GitHub, through an online API, and through R packages.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work. Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below: AIpert-pwllnod: Natural Sciences and Engineering Research Council of Canada; Caltech-CS156: Gary Clinard Innovation Fund; CEID-Walk: University of Georgia; CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook; COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health; Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information & Data Science Pilot Project; Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation; CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation; DDS-NBDS: NSF III-1812699; epiforecasts-ensemble1: Wellcome Trust (210758/Z/18/Z) FDANIHASU: supported by the Intramural Research Program of the NIH/NIDDK; GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowment, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines, CDC MInD-Healthcare U01CK000531-Supplement; IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096); Imperial-ensemble1: SB acknowledges funding from the Wellcome Trust (219415); Institute of Business Forecasting: IBF; IowaStateLW-STEM: NSF DMS-1916204, Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics; IUPUI CIS: NSF; JHU_CSSE-DECOM: JHU CSSE: National Science Foundation (NSF) RAPID Real-time Forecasting of COVID-19 risk in the USA. 2021-2022. Award ID: 2108526. National Science Foundation (NSF) RAPID Development of an interactive web-based dashboard to track COVID-19 in real-time. 2020. Award ID: 2028604; JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers for Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant); JHU_UNC_GAS-StatMechP ol: NIH NIGMS: R01GM140564; JHUAPL-Bucky: US Dept of Health and Human Services; KITmetricslab-select_ensemble: Daniel Wolffram gratefully acknowledges support by the Klaus Tschira Foundation; LANL-GrowthRate: LANL LDRD 20200700ER; MIT-Cassandra: MIT Quest for Intelligence; MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01; CA NU38OT000297 from the Council of State and Territorial Epidemiologists (CSTE); NotreDame-FRED: NSF RAPID DEB 2027718; NotreDame-mobility: NSF RAPID DEB 2027718; PSI-DRAFT: NSF RAPID Grant # 2031536; QJHong-Encounter: NSF DMR-2001411 and DMR-1835939; SDSC_ISG-TrendModel: The development of the dashboard was partly funded by the Fondation Privee des Hopitaux Universitaires de Geneve; UA-EpiCovDA: NSF RAPID Grant # 2028401; UChicagoCHATTOPADHYAY-UnIT: Defense Advanced Research Projects Agency (DARPA) #HR00111890043/P00004 (I. Chattopadhyay, University of Chicago); UCSB-ACTS: NSF RAPID IIS 2029626; UCSD_NEU-DeepGLEAM: Google Faculty Award, W31P4Q-21-C-0014; UMass-MechBayes: NIGMS #R35GM119582, NSF #1749854, NIGMS #R35GM119582; UMich-RidgeTfReg: This project is funded by the University of Michigan Physics Department and the University of Michigan Office of Research; UVA-Ensemble: National Institutes of Health (NIH) Grant 1R01GM109718, NSF BIG DATA Grant IIS-1633028, NSF Grant No.: OAC-1916805, NSF Expeditions in Computing Grant CCF-1918656, CCF-1917819, NSF RAPID CNS-2028004, NSF RAPID OAC-2027541, US Centers for Disease Control and Prevention 75D30119C05935, a grant from Google, University of Virginia Strategic Investment Fund award number SIF160, Defense Threat Reduction Agency (DTRA) under Contract No. HDTRA1-19-D-0007, and Virginia Dept of Health Grant VDH-21-501-0141; Wadnwani_AI-BayesOpt: This study is made possible by the generous support of the American People through the United States Agency for International Development (USAID). The work described in this article was implemented under the TRACETB Project, managed by WIAI under the terms of Cooperative Agreement Number 72038620CA00006. The contents of this manuscript are the sole responsibility of the authors and do not necessarily reflect the views of USAID or the United States Government; WalmartLabsML-LogForecasting: Team acknowledges Walmart to support this study Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesI confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.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.YesAll data produced are available online at https://github.com/reichlab/covid19-forecast-hub https://github.com/reichlab/covid19-forecast-hub |
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the US (preprint)
Cramer EY , Ray EL , Lopez VK , Bracher J , Brennen A , Castro Rivadeneira AJ , Gerding A , Gneiting T , House KH , Huang Y , Jayawardena D , Kanji AH , Khandelwal A , Le K , Mühlemann A , Niemi J , Shah A , Stark A , Wang Y , Wattanachit N , Zorn MW , Gu Y , Jain S , Bannur N , Deva A , Kulkarni M , Merugu S , Raval A , Shingi S , Tiwari A , White J , Abernethy NF , Woody S , Dahan M , Fox S , Gaither K , Lachmann M , Meyers LA , Scott JG , Tec M , Srivastava A , George GE , Cegan JC , Dettwiller ID , England WP , Farthing MW , Hunter RH , Lafferty B , Linkov I , Mayo ML , Parno MD , Rowland MA , Trump BD , Zhang-James Y , Chen S , Faraone SV , Hess J , Morley CP , Salekin A , Wang D , Corsetti SM , Baer TM , Eisenberg MC , Falb K , Huang Y , Martin ET , McCauley E , Myers RL , Schwarz T , Sheldon D , Gibson GC , Yu R , Gao L , Ma Y , Wu D , Yan X , Jin X , Wang YX , Chen Y , Guo L , Zhao Y , Gu Q , Chen J , Wang L , Xu P , Zhang W , Zou D , Biegel H , Lega J , McConnell S , Nagraj VP , Guertin SL , Hulme-Lowe C , Turner SD , Shi Y , Ban X , Walraven R , Hong QJ , Kong S , van de Walle A , Turtle JA , Ben-Nun M , Riley S , Riley P , Koyluoglu U , DesRoches D , Forli P , Hamory B , Kyriakides C , Leis H , Milliken J , Moloney M , Morgan J , Nirgudkar N , Ozcan G , Piwonka N , Ravi M , Schrader C , Shakhnovich E , Siegel D , Spatz R , Stiefeling C , Wilkinson B , Wong A , Cavany S , España G , Moore S , Oidtman R , Perkins A , Kraus D , Kraus A , Gao Z , Bian J , Cao W , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Vespignani A , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Xiong X , Zheng A , Baek J , Farias V , Georgescu A , Levi R , Sinha D , Wilde J , Perakis G , Bennouna MA , Nze-Ndong D , Singhvi D , Spantidakis I , Thayaparan L , Tsiourvas A , Sarker A , Jadbabaie A , Shah D , Della Penna N , Celi LA , Sundar S , Wolfinger R , Osthus D , Castro L , Fairchild G , Michaud I , Karlen D , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Lee EC , Dent J , Grantz KH , Hill AL , Kaminsky J , Kaminsky K , Keegan LT , Lauer SA , Lemaitre JC , Lessler J , Meredith HR , Perez-Saez J , Shah S , Smith CP , Truelove SA , Wills J , Marshall M , Gardner L , Nixon K , Burant JC , Wang L , Gao L , Gu Z , Kim M , Li X , Wang G , Wang Y , Yu S , Reiner RC , Barber R , Gakidou E , Hay SI , Lim S , Murray C , Pigott D , Gurung HL , Baccam P , Stage SA , Suchoski BT , Prakash BA , Adhikari B , Cui J , Rodríguez A , Tabassum A , Xie J , Keskinocak P , Asplund J , Baxter A , Oruc BE , Serban N , Arik SO , Dusenberry M , Epshteyn A , Kanal E , Le LT , Li CL , Pfister T , Sava D , Sinha R , Tsai T , Yoder N , Yoon J , Zhang L , Abbott S , Bosse NI , Funk S , Hellewell J , Meakin SR , Sherratt K , Zhou M , Kalantari R , Yamana TK , Pei S , Shaman J , Li ML , Bertsimas D , Skali Lami O , Soni S , Tazi Bouardi H , Ayer T , Adee M , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller P , Xiao J , Wang Y , Wang Q , Xie S , Zeng D , Green A , Bien J , Brooks L , Hu AJ , Jahja M , McDonald D , Narasimhan B , Politsch C , Rajanala S , Rumack A , Simon N , Tibshirani RJ , Tibshirani R , Ventura V , Wasserman L , O'Dea EB , Drake JM , Pagano R , Tran QT , Ho LST , Huynh H , Walker JW , Slayton RB , Johansson MA , Biggerstaff M , Reich NG . medRxiv 2021 2021.02.03.21250974 Short-term probabilistic forecasts of the trajectory of the COVID-19 pandemic in the United States have served as a visible and important communication channel between the scientific modeling community and both the general public and decision-makers. Forecasting models provide specific, quantitative, and evaluable predictions that inform short-term decisions such as healthcare staffing needs, school closures, and allocation of medical supplies. In 2020, the COVID-19 Forecast Hub (https://covid19forecasthub.org/) collected, disseminated, and synthesized hundreds of thousands of specific predictions from more than 50 different academic, industry, and independent research groups. This manuscript systematically evaluates 23 models that regularly submitted forecasts of reported weekly incident COVID-19 mortality counts in the US at the state and national level. One of these models was a multi-model ensemble that combined all available forecasts each week. The performance of individual models showed high variability across time, geospatial units, and forecast horizons. Half of the models evaluated showed better accuracy than a naïve baseline model. In combining the forecasts from all teams, the ensemble showed the best overall probabilistic accuracy of any model. Forecast accuracy degraded as models made predictions farther into the future, with probabilistic accuracy at a 20-week horizon more than 5 times worse than when predicting at a 1-week horizon. This project underscores the role that collaboration and active coordination between governmental public health agencies, academic modeling teams, and industry partners can play in developing modern modeling capabilities to support local, state, and federal response to outbreaks.Competing Interest StatementAV, MC, and APP report grants from Metabiota Inc outside the submitted work.Funding StatementFor teams that reported receiving funding for their work, we report the sources and disclosures below. CMU-TimeSeries: CDC Center of Excellence, gifts from Google and Facebook. CU-select: NSF DMS-2027369 and a gift from the Morris-Singer Foundation. COVIDhub: This work has been supported by the US Centers for Disease Control and Prevention (1U01IP001122) and the National Institutes of General Medical Sciences (R35GM119582). The content is solely the responsibility of the authors and does not necessarily represent the official views of CDC, NIGMS or the National Institutes of Health. Johannes Bracher was supported by the Helmholtz Foundation via the SIMCARD Information& Data Science Pilot Project. Tilmann Gneiting gratefully acknowledges support by the Klaus Tschira Foundation. DDS-NBDS: NSF III-1812699. EPIFORECASTS-ENSEMBLE1: Wellcome Trust (210758/Z/18/Z) GT_CHHS-COVID19: William W. George Endowment, Virginia C. and Joseph C. Mello Endowments, NSF DGE-1650044, NSF MRI 1828187, research cyberinfrastructure resources and services provided by the Partnership for an Advanced Computing Environment (PACE) at Georgia Tech, and the following benefactors at Georgia Tech: Andrea Laliberte, Joseph C. Mello, Richard Rick E. & Charlene Zalesky, and Claudia & Paul Raines GT-DeepCOVID: CDC MInD-Healthcare U01CK000531-Supplement. NSF (Expeditions CCF-1918770, CAREER IIS-2028586, RAPID IIS-2027862, Medium IIS-1955883, NRT DGE-1545362), CDC MInD program, ORNL and funds/computing resources from Georgia Tech and GTRI. IHME: This work was supported by the Bill & Melinda Gates Foundation, as well as funding from the state of Washington and the National Science Foundation (award no. FAIN: 2031096). IowaStateLW-STEM: Iowa State University Plant Sciences Institute Scholars Program, NSF DMS-1916204, NSF CCF-1934884, Laurence H. Baker Center for Bioinformatics and Biological Statistics. JHU_IDD-CovidSP: State of California, US Dept of Health and Human Services, US Dept of Homeland Security, US Office of Foreign Disaster Assistance, Johns Hopkins Health System, Office of the Dean at Johns Hopkins Bloomberg School of Public Health, Johns Hopkins University Modeling and Policy Hub, Centers fo Disease Control and Prevention (5U01CK000538-03), University of Utah Immunology, Inflammation, & Infectious Disease Initiative (26798 Seed Grant). LANL-GrowthRate: LANL LDRD 20200700ER. MOBS-GLEAM_COVID: COVID Supplement CDC-HHS-6U01IP001137-01. NotreDame-mobility and NotreDame-FRED: NSF RAPID DEB 2027718 UA-EpiCovDA: NSF RAPID Grant # 2028401. UCSB-ACTS: NSF RAPID IIS 2029626. UCSD-NEU: Google Faculty Award, DARPA W31P4Q-21-C-0014, COVID Supplement CDC-HHS-6U01IP001137-01. UMass-MechBayes: NIGMS R35GM119582, NSF 1749854. UMich-RidgeTfReg: The University of Michigan Physics Department and the University of Michigan Office of Research.Author DeclarationsI confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.YesThe details of the IRB/oversight body that provided approval or exemption for the research described are given below:UMass-Amherst IRBAll 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.YesAll data and code referred to in the manuscript are publicly available. https://github.com/reichlab/covid19-forecast-hub/ https://github.com/reichlab/covidEnsembles https://zoltardata.com/project/44 |
Guiding Vaccine Efficacy Trial Design During Public Health Emergencies: An interactive web-based decision support tool (preprint)
Bellan SE , Eggo RM , Gsell PS , Kucharski AJ , Dean NE , Donohue R , Zook M , Odhiambo F , Longini IM Jr , Brisson M , Mahon BE , Henao-Restrepo AM . bioRxiv 2018 252783 The design and execution of rigorous, fast, and ethical vaccine efficacy trials can be challenging during epidemics of emerging pathogens, such as the 2014-2016 Ebola virus and 2015-2016 Zika virus epidemics. Response to an urgent public health crisis requires accelerated research even as emerging epidemics themselves change rapidly and are inherently less well understood than well-established diseases. As part of the World Health Organization Research and Development Blueprint, we designed a web-based interactive decision support system (InterVax-Tool) to help diverse stakeholders navigate the epidemiological, logistical, and ethical decisions involved in designing a vaccine efficacy trial during a public health emergency. In contrast to existing literature on trial design, InterVax-Tool offers high-level visual and interactive assistance through a set of four decision trees, guiding users through selection of 1) the Primary Endpoint, (2) the Target Population, (3) Randomization, and (4) the Comparator. Guidance is provided on how each of fourteen key considerations–grouped as Epidemiological, Vaccine-related, Infrastructural, or Sociocultural–should be used to inform each decision in the trial design process. The tool is not intended to provide a black box decision framework for identifying an optimal trial design, but rather to facilitate transparent, collaborative and comprehensive discussion of the relevant decisions, while recording the decision process. The tool can also assist capacity building by providing a cross-disciplinary picture of trial design using concepts from epidemiology, study design, vaccinology, biostatistics, mathematical modeling and clinical research ethics. Here, we describe the goals and features of InterVax-Tool as well as its application to the design of a Zika vaccine efficacy trial.One Sentence Summary An interactive web-based decision support tool was developed to assist in the design of vaccine efficacy trials during emerging outbreaks. |
Impact of close interpersonal contact on COVID-19 incidence: evidence from one year of mobile device data (preprint)
Crawford FW , Jones SA , Cartter M , Dean SG , Warren JL , Li ZR , Barbieri J , Campbell J , Kenney P , Valleau T , Morozova O . medRxiv 2021 Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We sought to quantify interpersonal contact at the population-level by using anonymized mobile device geolocation data. We computed the frequency of contact (within six feet) between people in Connecticut during February 2020 - January 2021. Then we aggregated counts of contact events by area of residence to obtain an estimate of the total intensity of interpersonal contact experienced by residents of each town for each day. When incorporated into a susceptible-exposed-infective-removed (SEIR) model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns during the timespan. The pattern of contact rate in Connecticut explains the large initial wave of infections during March-April, the subsequent drop in cases during June-August, local outbreaks during August-September, broad statewide resurgence during September-December, and decline in January 2021. Contact rate data can help guide public health messaging campaigns to encourage social distancing and in the allocation of testing resources to detect or prevent emerging local outbreaks more quickly than traditional case investigation. ONE SENTENCE SUMMARY: Close interpersonal contact measured using mobile device location data explains dynamics of COVID-19 transmission in Connecticut during the first year of the pandemic. |
Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis (preprint)
Joseph SJ , Bommana S , Ziklo N , Kama M , Dean D , Read TD . bioRxiv 2023 26 Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. The 78 C. trachomatis genomes from participants were from two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorecta"l clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. The absence of large numbers of fixed SNPs between C. trachomatis strains within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant variation in the different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-ND 4.0 International license. |
Changes in spina bifida lesion level after folic acid fortification in the US
Mai CT , Evans J , Alverson CJ , Yue X , Flood T , Arnold K , Nestoridi E , Denson L , Adisa O , Moore CA , Nance A , Zielke K , Rice S , Shan X , Dean JH , Ethen M , Hansen B , Isenburg J , Kirby RS . Obstet Gynecol Surv 2023 78 (4) 189-191 following which a substantial decline in neural tube defects at birth occurred. Studies also have suggested that lesion levels in cases of spina bifida are directly affected by folic acid fortification. Locations of such lesions contribute to outcome and prognosis of the condition. When compared with sacral and lower lumbar lesions, the greatest risks of disability and mortality are associated with cervical, thoracic, and high lumbar lesions. Individuals with thoracic or high lumbar lesions require a wheelchair and orthosis in adulthood for ambulation 70% to 99% of the time. As lesion levels therefore determine function and overall quality of life, assessment of whether folic acid fortification significantly impacts lesion levels is important. This study aimed to examine patterns of lesion levels in spina bifida following mandatory folic acid fortification in the United States. | | A call was issued by the National Birth Defects Prevention Network for State Birth Defects Programs' spina bifida lesion data before and after fortification mandate. To be eligible, programs needed to provide verbatim medical record text descriptions of spina bifida diagnoses. The 6 participating programs were from the states of Arizona, California (covering 8 counties), Oklahoma, South Carolina, Utah, and metropolitan Atlanta (Georgia). Birth years examined included the prefortification years of 1992–1996 and the postfortification period of 1999–2016. Central processing and analysis occurred as each program provided case-level data (deidentified) based on the exclusion/inclusion criteria to the Centers for Disease Control and Prevention. Medical and record text description of the spina bifida diagnosis and codes were the basis of case information, using the International Classification of Diseases, Ninth Edition, Clinical Modification or the Centers for Disease Control and Prevention and Prevention/British Pediatric Association coding system. Types of spina bifida included in the study were spinal rachischisis, myelomeningocele/meningomyelocele, meningocele, and spina bifida not otherwise specified. Cases excluded were cranial lesions, lipomyelomeningocele/lipomeningomyelocele, dysraphism related to split cord malformations, and spina bifida occulta. | | Lesion-level information was provided based on the highest lesion using nonradiographic clinical assessment. Classification of severe upper-level lesions included cervical or thoracic lesion-level cases, whereas lower-level lesions included cases with lumbar or sacral. The study defined open lesion as leaking spinal fluid or membrane covered only, whereas closed lesions were defined as having intact-skin covering and lacking fluid leakage. Spina bifida cases were considered isolated when no other anomalies related to the primary cause of abnormal neural tube closure were present (nor were secondary to the neurologic complications caused by it). Examining associations between fortification period and the outcomes (lesion level and spina bifida) occurred using the generalized estimating approach to logistic (case severity analyses) and log-linear (PR analyses) regression, which accounted for clustering of cases by state. | | From a total of 7,816,062 live births, 2593 cases of spina bifida met the case inclusion criteria. Overall, 573 cases were included in the prefortification period (birth prevalence of 4.07 per 10,000 live births), and 2020 cases were included in the postfortification period (birth prevalence of 3.15 per 10,000 live births). Overall, 80.2% of cases resulted in live births, and most cases of spina bifida involved lower-level lesions (81.3%). Most lesions were lumbar, and the proportions prefortification and postfortification were 61.4% and 72.0%, respectively, with a higher proportion of lumbar lesions seen in the postfortification period. The odds of upper-level to lower-level lesions decreased by 70% after fortification. The spina bifida live birth prevalence decreased significantly and remained consistently low throughout the early, mid, and recent postfortification periods. The study found a 72% decrease overall in prevalence of severe, upper-level lesions following mandatory folic acid fortification in the United States. | | The limitations of the study include the shortcomings of relying on diagnostic codes, the difficulty of coding lesion level using the International Classification of Diseases, Ninth Edition, Clinical Modification coding scheme, the lack of recorded functional outcome for children in medical records (indirect indicators of severity), the lack of preconception and prenatal folic acid data, and the possible variation of case ascertainment within programs contributing studies. A major study strength is its potential to address additional important questions regarding epidemiology and spina bifida. The classification of spinal defects is complex, and this study adds to the limited distribution data that exist for prefortification and postfortification subtypes. | | The study concluded that the overall prevalence of severe upper-level lesions in spina bifida cases experienced a steep reduction following mandatory folic acid fortification institution within the United States, whereas no change in the prevalence of less severe lower-level lesions took place. Additional examinations are warranted to better understand the magnitude and mechanism of spina bifida severity in relation to folic acid intake. |
Surveillance Indicators for Women's Preconception Care
Surveillance and Research Workgroup and Clinical Workgroup of the National Preconception Health and Health Care Initiative , Adamski Alys , Bernstein Peter S , Boulet Sheree L , Chowdhury Farah M , D’Angelo Denise V , Coonrod Dean V , Frayne Daniel J , Kroelinger Charlan , Morgan Isabel A , Okoroh Ekwutosi M , Olson Christine K , Robbins Cheryl L , Verbiest Sarah . J Womens Health (Larchmt) 2020 29 (7) 910-918 Background: Limited surveillance of preconception care (PCC) impedes states' ability to monitor access and provision of quality PCC. In response, we describe PCC indicators and the evaluation process used to identify a set of PCC indicators for state use. Materials and Methods: The Surveillance and Research Workgroup and Clinical Workgroup of the National Preconception Health and Health Care Initiative used a systematic process to identify, evaluate, and prioritize PCC indicators from nationwide public health surveillance systems that Maternal and Child Health (MCH) programs can use for state-level surveillance using the Pregnancy Risk Assessment Monitoring System (PRAMS) and Behavioral Risk Factor Surveillance System (BRFSS). For each indicator, we assessed target population, prevalence, measurement simplicity, data availability, clinical utility, and whether it was related to the 10 prioritized preconception health indicators. We also assessed relevance to clinical recommendations, Healthy People (HP)2020 objectives, and the National Quality Forum measures. Lastly, we considered input from stakeholders and subject matter experts. Results: Eighty potential PCC indicators were initially identified. After conducting evaluations, obtaining stakeholder input, and consulting with subject matter experts, the list was narrowed to 30 PCC indicators for states to consider using in their MCH programs to inform the need for new strategies and monitor programmatic activities. PRAMS is the data source for 27 of the indicators, and BRFSS is the data source for three indicators. Conclusions: The identification and evaluation of population-based PCC indicators that are available at the state level increase opportunities for state MCH programs to document, monitor, and address PCC in their locales. |
Patterns of within-host spread of Chlamydia trachomatis between vagina, endocervix and rectum revealed by comparative genomic analysis
Joseph SJ , Bommana S , Ziklo N , Kama M , Dean D , Read TD . Front Microbiol 2023 14 1154664 INTRODUCTION: Chlamydia trachomatis, a gram-negative obligate intracellular bacterium, commonly causes sexually transmitted infections (STIs). Little is known about C. trachomatis transmission within the host, which is important for understanding disease epidemiology and progression. METHODS: We used RNA-bait enrichment and whole-genome sequencing to compare rectal, vaginal and endocervical samples collected at the same time from 26 study participants who attended Fijian Ministry of Health and Medical Services clinics and tested positive for C. trachomatis at each anatomic site. RESULTS: The 78 C. trachomatis genomes from participants resolved into two major clades of the C. trachomatis phylogeny (the "prevalent urogenital and anorectal" clade and "non-prevalent urogenital and anorectal" clade). For 21 participants, genome sequences were almost identical in each anatomic site. For the other five participants, two distinct C. trachomatis strains were present in different sites; in two cases, the vaginal sample was a mixture of strains. DISCUSSION: The absence of large numbers of fixed SNPs between C. trachomatis genomes within many of the participants could indicate recent acquisition of infection prior to the clinic visit without sufficient time to accumulate significant genetic variation in different body sites. This model suggests that many C. trachomatis infections may be resolved relatively quickly in the Fijian population, possibly reflecting common prescription or over-the-counter antibiotics usage. |
Secondhand smoke exposure inside the home among adults in eight countries in Sub-Saharan Africa: Global Adult Tobacco Survey, 2012-2018
Mbulo L , Palipudi K , Smith T , Owusu D , Williams F , Dean AK , Mamudu HM . Nicotine Tob Res 2022 25 (4) 828-837 INTRODUCTION: Secondhand tobacco smoke (SHS) exposure causes diseases and death in adults and children. Evidence indicates that most SHS exposures occur at home and in workplace. Therefore, home is a major place where adults and children can be effectively protected from SHS. This study examined the magnitude of SHS exposure at home and associated factors in eight sub-Saharan African countries. METHODS: We analyzed 2012-2018 Global Adult Tobacco Survey data for Botswana, Cameroon, Ethiopia, Kenya, Nigeria, Senegal, Tanzania, and Uganda. We computed prevalence estimates of self-reported monthly SHS exposure at home reported as anyone smoke inside their home daily, weekly or monthly. We calculated SHS exposure at home prevalence and applied multivariable logistic regression models to identify related factors. RESULTS: Overall median prevalence of SHS exposure at home was 13.8% in the eight countries; ranging from 6.6% (95% CI: 5.7%, 7.6%) in Nigeria to 21.6% (95% CI: 19.4%, 24.0%) in Senegal. In multivariable analysis across the countries, SHS exposure at home was associated with living with a smoker, ranging from an adjusted odds ratio (aOR) of 4.6 (95% CI: 3.6, 5.8) in Botswana to 27.6 (95% CI: 20.1, 37.8) in Nigeria. SHS exposure at home was significantly associated with lower education attainment (Kenya, and Ethiopia), and lower wealth index (Uganda, Senegal, and Botswana). CONCLUSION: SHS exposure in homes was associated with the presence of a smoker in the home and lower socioeconomic status. |
Changes in spina bifida lesion level after folic acid fortification in the United States
Mai CT , Evans J , Alverson CJ , Yue X , Flood T , Arnold K , Nestoridi E , Denson L , Adisa O , Moore CA , Nance A , Zielke K , Rice S , Shan X , Dean JH , Ethen M , Hansen B , Isenburg J , Kirby RS . J Pediatr 2022 249 59-66 e1 OBJECTIVE: To assess whether the severity of cases of spina bifida changed after mandatory folic acid fortification in the United States. STUDY DESIGN: Six active population-based birth defects programs provided data on cases of spina bifida for 1992-1996 (pre-fortification) and 1999-2016 (post-fortification); programs contributed varying years of data. Case information included both medical record verbatim text description of the spina bifida diagnosis and spina bifida codes (International Classification of Diseases, Clinical Modification, or a modified birth defects surveillance coding system). Comparing pre- with post-fortification periods, adjusted odds ratios (aOR) for case severity [upper-level (cervical, thoracic) to lower-level (lumbar, sacral) lesion cases] and prevalence ratios (PR) were estimated. RESULTS: A total of 2,593 cases of spina bifida (7,816,062 live births) met inclusion criteria, with 573 and 2,020 cases from the pre- and post-fortification periods respectively. Case severity decreased 70% (aOR: 0.30; 95% confidence interval [CI] 0.26, 0.35) between the fortification periods. The decrease was most pronounced for non-Hispanic white mothers. Overall spina bifida prevalence declined 23% (PR=0.77, 95% CI=0.71, 0.85), with similar reduction seen across early, mid, and recent post-fortification periods. A statistically significant decrease in upper-level lesions occurred in the post-fortification compared with pre-fortification periods (PR=0.28, 95% CI=0.22, 0.34), while prevalence of lower-level lesions remained relatively similar (PR: 0.94, 95% CI: 0.84, 1.05). CONCLUSIONS: Severity of cases of spina bifida decreased after mandatory folic acid fortification in the United States. Further examination is warranted to understand better the potential effect of folic acid on spina bifida severity. |
Electronic cigarette use among adults in 14 countries: A cross-sectional study
Pan L , Morton J , Mbulo L , Dean A , Ahluwalia IB . EClinicalMedicine 2022 47 101401 BACKGROUND: The tobacco product landscape continues to change. No recent data for electronic cigarette (e-cigarette) use have been reported for multiple countries based on nationally representative surveys. We examined prevalence of e-cigarette use and variations by sociodemographic characteristics in 14 countries using Global Adult Tobacco Survey (GATS) data between Jan 1, 2015, and Dec 31, 2018. METHODS: GATS is a nationally representative household survey of tobacco use among adults aged ≥15 years. The analytic sample size ranged from 4347 in Senegal to 74,037 in India. Prevalence of current e-cigarette use was stratified by sociodemographic subgroups. Age-standardized prevalence was estimated according to world 2000-2025 standard population. Significant differences in adjusted prevalence across sociodemographic subgroup was determined by p value for marginal effect contrast in multivariable logistic regression models. FINDINGS: More than 50% of adults in Russia, Romania, and Ukraine and additionally more than 30% of adults in China, Costa Rica, Uruguay, Mexico, and Philippines were aware of e-cigarettes. Crude prevalence of current e-cigarette use ranged from 0.02% (95% CI 0.01%-0.04%) in India to 3.5% (2.9%-4.2%) in Russia. Prevalence was <1% in nine countries. Approximately 18.3 million adults currently used e-cigarettes across the 14 countries. Men had a significantly higher prevalence of current e-cigarette use than women in eight countries. Additionally, higher adjusted prevalence was observed in some countries among young adults aged 15‒24 years, urban residents, and adults with higher education levels and higher wealth index. INTERPRETATION: The study provides needed baseline data on e-cigarette awareness and use. Continued surveillance is essential to inform interventions and policies to prevent initiation and enhance cessation support. FUNDING: None. |
Impact of close interpersonal contact on COVID-19 incidence: Evidence from 1 year of mobile device data.
Crawford FW , Jones SA , Cartter M , Dean SG , Warren JL , Li ZR , Barbieri J , Campbell J , Kenney P , Valleau T , Morozova O . Sci Adv 2022 8 (1) eabi5499 Close contact between people is the primary route for transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). We quantified interpersonal contact at the population level using mobile device geolocation data. We computed the frequency of contact (within 6 feet) between people in Connecticut during February 2020 to January 2021 and aggregated counts of contact events by area of residence. When incorporated into a SEIR-type model of COVID-19 transmission, the contact rate accurately predicted COVID-19 cases in Connecticut towns. Contact in Connecticut explains the initial wave of infections during March to April, the drop in cases during June to August, local outbreaks during August to September, broad statewide resurgence during September to December, and decline in January 2021. The transmission model fits COVID-19 transmission dynamics better using the contact rate than other mobility metrics. Contact rate data can help guide social distancing and testing resource allocation. |
Single dose of chimeric dengue-2/Zika vaccine candidate protects mice and non-human primates against Zika virus.
Baldwin WR , Giebler HA , Stovall JL , Young G , Bohning KJ , Dean HJ , Livengood JA , Huang CY . Nat Commun 2021 12 (1) 7320 The development of a safe and effective Zika virus (ZIKV) vaccine has become a global health priority since the widespread epidemic in 2015-2016. Based on previous experience in using the well-characterized and clinically proven dengue virus serotype-2 (DENV-2) PDK-53 vaccine backbone for live-attenuated chimeric flavivirus vaccine development, we developed chimeric DENV-2/ZIKV vaccine candidates optimized for growth and genetic stability in Vero cells. These vaccine candidates retain all previously characterized attenuation phenotypes of the PDK-53 vaccine virus, including attenuation of neurovirulence for 1-day-old CD-1 mice, absence of virulence in interferon receptor-deficient mice, and lack of transmissibility in the main mosquito vectors. A single DENV-2/ZIKV dose provides protection against ZIKV challenge in mice and rhesus macaques. Overall, these data indicate that the ZIKV live-attenuated vaccine candidates are safe, immunogenic and effective at preventing ZIKV infection in multiple animal models, warranting continued development. |
Theoretical framework for retrospective studies of the effectiveness of SARS-CoV-2 vaccines.
Lewnard JA , Patel MM , Jewell NP , Verani JR , Kobayashi M , Tenforde MW , Dean NE , Cowling BJ , Lopman BA . Epidemiology 2021 32 (4) 508-517 Observational studies of the effectiveness of vaccines to prevent COVID-19 are needed to inform real-world use. Such studies are now underway amid the ongoing rollout of SARS-CoV-2 vaccines globally. Although traditional case-control and test-negative design studies feature prominently among strategies used to assess vaccine effectiveness, such studies may encounter important threats to validity. Here, we review the theoretical basis for estimation of vaccine direct effects under traditional case-control and test-negative design frameworks, addressing specific natural history parameters of SARS-CoV-2 infection and COVID-19 relevant to these designs. Bias may be introduced by misclassification of cases and controls, particularly when clinical case criteria include common, nonspecific indicators of COVID-19. When using diagnostic assays with high analytical sensitivity for SARS-CoV-2 detection, individuals testing positive may be counted as cases even if their symptoms are due to other causes. The traditional case-control design may be particularly prone to confounding due to associations of vaccination with healthcare-seeking behavior or risk of infection. The test-negative design reduces but may not eliminate this confounding, for instance, if individuals who receive vaccination seek care or testing for less-severe illness. These circumstances indicate the two study designs cannot be applied naively to datasets gathered through public health surveillance or administrative sources. We suggest practical strategies to reduce bias in vaccine effectiveness estimates at the study design and analysis stages. |
Modeling of Future COVID-19 Cases, Hospitalizations, and Deaths, by Vaccination Rates and Nonpharmaceutical Intervention Scenarios - United States, April-September 2021.
Borchering RK , Viboud C , Howerton E , Smith CP , Truelove S , Runge MC , Reich NG , Contamin L , Levander J , Salerno J , van Panhuis W , Kinsey M , Tallaksen K , Obrecht RF , Asher L , Costello C , Kelbaugh M , Wilson S , Shin L , Gallagher ME , Mullany LC , Rainwater-Lovett K , Lemaitre JC , Dent J , Grantz KH , Kaminsky J , Lauer SA , Lee EC , Meredith HR , Perez-Saez J , Keegan LT , Karlen D , Chinazzi M , Davis JT , Mu K , Xiong X , Pastore YPiontti A , Vespignani A , Srivastava A , Porebski P , Venkatramanan S , Adiga A , Lewis B , Klahn B , Outten J , Schlitt J , Corbett P , Telionis PA , Wang L , Peddireddy AS , Hurt B , Chen J , Vullikanti A , Marathe M , Healy JM , Slayton RB , Biggerstaff M , Johansson MA , Shea K , Lessler J . MMWR Morb Mortal Wkly Rep 2021 70 (19) 719-724 After a period of rapidly declining U.S. COVID-19 incidence during January-March 2021, increases occurred in several jurisdictions (1,2) despite the rapid rollout of a large-scale vaccination program. This increase coincided with the spread of more transmissible variants of SARS-CoV-2, the virus that causes COVID-19, including B.1.1.7 (1,3) and relaxation of COVID-19 prevention strategies such as those for businesses, large-scale gatherings, and educational activities. To provide long-term projections of potential trends in COVID-19 cases, hospitalizations, and deaths, COVID-19 Scenario Modeling Hub teams used a multiple-model approach comprising six models to assess the potential course of COVID-19 in the United States across four scenarios with different vaccination coverage rates and effectiveness estimates and strength and implementation of nonpharmaceutical interventions (NPIs) (public health policies, such as physical distancing and masking) over a 6-month period (April-September 2021) using data available through March 27, 2021 (4). Among the four scenarios, an accelerated decline in NPI adherence (which encapsulates NPI mandates and population behavior) was shown to undermine vaccination-related gains over the subsequent 2-3 months and, in combination with increased transmissibility of new variants, could lead to surges in cases, hospitalizations, and deaths. A sharp decline in cases was projected by July 2021, with a faster decline in the high-vaccination scenarios. High vaccination rates and compliance with public health prevention measures are essential to control the COVID-19 pandemic and to prevent surges in hospitalizations and deaths in the coming months. |
Leading Organizational Change: Improved Leadership Behaviors Among Public Health Leaders After Receiving Multirater Feedback and Coaching
Spears-Jones C , Myles R , Porch T , Parris S , Ivy-Knudsen M , Dean HD . Workplace Health Saf 2021 69 (9) 21650799211001728 BACKGROUND: Leading Change is one of five Executive Core Qualifications (ECQs) used in developing leaders in the federal government. Leadership development programs that incorporate multirater feedback and executive coaching are valuable in developing competencies to lead change. METHODS: We examined the extent by which coaching influenced Leading Change competencies and identified effective tools and resources used to enhance the leadership capacity of first- and midlevel leaders at Centers for Disease Control and Prevention's National Center for HIV/AIDS, Viral Hepatitis, Sexually Transmitted Diseases, and Tuberculosis Prevention. Data included qualitative data collected via semi-structured interviews that focused on leadership changes made by leaders in the Coaching and Leadership Initiative (CaLI), a leadership development program for Team Leads and Branch Chiefs. FINDINGS: Ninety-six participants completed leadership coaching; 94 (98%) of whom completed one or more interviews. Of those 94 respondents, 74 (79%) reported improvements in their ability to lead change in 3 of 4 leading change competencies: creativity and innovation, flexibility, and resilience. All respondents indicated tools and resources that were effective in leading change: 49 (52%) participated in instructor-led activities during their CaLI experience; 33 (35%) experiential activities; 94 (100%) developmental relationships, assessment, and feedback; and 25 (27%) self-development. CONCLUSIONS/APPLICATION TO PRACTICE: First- and midlevel leaders in a public health agency benefitted from using leadership coaching in developing competencies to lead organizational change. Leadership development programs might benefit from examining Leading Change competencies and including instructor-led and experiential activities as an additional component of a comprehensive leadership development program. |
Whole-Genome Enrichment and Sequencing of Chlamydia trachomatis Directly from Patient Clinical Vaginal and Rectal Swabs.
Bowden KE , Joseph SJ , Cartee JC , Ziklo N , Danavall D , Raphael BH , Read TD , Dean D . mSphere 2021 6 (2) Chlamydia trachomatis, an obligately intracellular bacterium, is the most prevalent cause of bacterial sexually transmitted infections (STIs) worldwide. Numbers of U.S. infections of the urogenital tract and rectum have increased annually. Because C. trachomatis is not easily cultured, comparative genomic studies are limited, restricting our understanding of strain diversity and emergence among populations globally. While Agilent SureSelect(XT) target enrichment RNA bait libraries have been developed for whole-genome enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal samples, public access to these libraries is not available. We therefore designed an RNA bait library (34,795 120-mer probes based on 85 genomes, versus 33,619 probes using 74 genomes in a previous one) to augment organism sequencing from clinical samples that can be shared with the scientific community, enabling comparison studies. We describe the library and limit of detection for genome copy input, and we present results of 100% efficiency and high-resolution determination of recombination and identical genomes within vaginal-rectal specimen pairs in women. This workflow provides a robust approach for discerning genomic diversity and advancing our understanding of the molecular epidemiology of contemporary C. trachomatis STIs across sample types, geographic populations, sexual networks, and outbreaks associated with proctitis/proctocolitis among women and men who have sex with men.IMPORTANCE Chlamydia trachomatis is an obligate intracellular bacterium that is not easily cultured, which limits our understanding of urogenital and rectal C. trachomatis transmission and impact on morbidity. To provide a publicly available workflow for whole-genome target enrichment and sequencing of C. trachomatis directly from clinical urine, vaginal, conjunctival, and rectal specimens, we developed and report on an RNA bait library to enrich the organism from clinical samples for sequencing. We demonstrate an increased efficiency in the percentage of reads mapping to C. trachomatis and identified recombinant and identical C. trachomatis genomes in paired vaginal-rectal samples from women. Our workflow provides a robust genomic epidemiologic approach to advance our understanding of C. trachomatis strains causing ocular, urogenital, and rectal infections and to explore geo-sexual networks, outbreaks of colorectal infections among women and men who have sex with men, and the role of these strains in morbidity. |
Tobacco smoking cessation and quitline use among adults aged 15 years in 31 countries: Findings from the Global Adult Tobacco Survey
Ahluwalia IB , Tripp AL , Dean AK , Mbulo L , Arrazola RA , Twentyman E , King BA . Am J Prev Med 2021 60 (3) S128-S135 Introduction: About 80% of the 1.1 billion people who smoke tobacco worldwide reside in low- and middle-income countries. Evidence-based approaches to promote cessation include brief advice from health professionals and referrals through quitlines. This study assesses cessation behaviors and the use of cessation services in the past 12 months among current tobacco smokers in 31 countries who attempted to quit. Methods: Data came from the Global Adult Tobacco Survey, a household-based survey of non-institutionalized adults aged ≥15 years. Surveys were conducted in 31 countries during 2008–2018; sample sizes ranged from 4,250 (Malaysia) to 74,037 (India), and response rates ranged from 64.4% (Ukraine) to 98.5% (Qatar). In 2019, data from the 31 countries were assessed in June 2019, and indicators included self-reported current (daily or less than daily) tobacco smoking, past-year quit attempts, and cessation methods used in the past 12 months. Results: Current tobacco smoking prevalence ranged from 3.7% (Ethiopia) to 38.2% (Greece). Overall, an estimated 176.8 million adults from the 31 countries made a quit attempt in the past 12 months, with country-level prevalence ranging from 16.4% (Greece) to 54.7% (Botswana). Most individuals who made a quit attempt did so without assistance (median=74.4%). Other methods were less prevalent, including quitlines (median=0.2%) and counseling (median=7.2%). Conclusions: In the assessed countries, the majority of those who currently smoked tobacco and made a quit attempt did so without assistance; very few reported using quitlines, partly because of the lack of quitlines in some countries. In resource-limited settings, quitlines can play a greater role in helping people quit smoking as part of a comprehensive approach. |
Bacterial genome-wide association study of hyper-virulent pneumococcal serotype 1 identifies genetic variation associated with neurotropism.
Chaguza C , Yang M , Cornick JE , du Plessis M , Gladstone RA , Kwambana-Adams BA , Lo SW , Ebruke C , Tonkin-Hill G , Peno C , Senghore M , Obaro SK , Ousmane S , Pluschke G , Collard JM , Sigaùque B , French N , Klugman KP , Heyderman RS , McGee L , Antonio M , Breiman RF , von Gottberg A , Everett DB , Kadioglu A , Bentley SD . Commun Biol 2020 3 (1) 559 Hyper-virulent Streptococcus pneumoniae serotype 1 strains are endemic in Sub-Saharan Africa and frequently cause lethal meningitis outbreaks. It remains unknown whether genetic variation in serotype 1 strains modulates tropism into cerebrospinal fluid to cause central nervous system (CNS) infections, particularly meningitis. Here, we address this question through a large-scale linear mixed model genome-wide association study of 909 African pneumococcal serotype 1 isolates collected from CNS and non-CNS human samples. By controlling for host age, geography, and strain population structure, we identify genome-wide statistically significant genotype-phenotype associations in surface-exposed choline-binding (P = 5.00 × 10(-08)) and helicase proteins (P = 1.32 × 10(-06)) important for invasion, immune evasion and pneumococcal tropism to CNS. The small effect sizes and negligible heritability indicated that causation of CNS infection requires multiple genetic and other factors reflecting a complex and polygenic aetiology. Our findings suggest that certain pathogen genetic variation modulate pneumococcal survival and tropism to CNS tissue, and therefore, virulence for meningitis. |
The TIRS trial: protocol for a cluster randomized controlled trial assessing the efficacy of preventive targeted indoor residual spraying to reduce Aedes-borne viral illnesses in Merida, Mexico
Manrique-Saide P , Dean NE , Halloran ME , Longini IM , Collins MH , Waller LA , Gomez-Dantes H , Lenhart A , Hladish TJ , Che-Mendoza A , Kirstein OD , Romer Y , Correa-Morales F , Palacio-Vargas J , Mendez-Vales R , Pérez PG , Pavia-Ruz N , Ayora-Talavera G , Vazquez-Prokopec GM . Trials 2020 21 (1) 839 BACKGROUND: Current urban vector control strategies have failed to contain dengue epidemics and to prevent the global expansion of Aedes-borne viruses (ABVs: dengue, chikungunya, Zika). Part of the challenge in sustaining effective ABV control emerges from the paucity of evidence regarding the epidemiological impact of any Aedes control method. A strategy for which there is limited epidemiological evidence is targeted indoor residual spraying (TIRS). TIRS is a modification of classic malaria indoor residual spraying that accounts for Aedes aegypti resting behavior by applying residual insecticides on exposed lower sections of walls (< 1.5 m), under furniture, and on dark surfaces. METHODS/DESIGN: We are pursuing a two-arm, parallel, unblinded, cluster randomized controlled trial to quantify the overall efficacy of TIRS in reducing the burden of laboratory-confirmed ABV clinical disease (primary endpoint). The trial will be conducted in the city of Merida, Yucatan State, Mexico (population ~ 1million), where we will prospectively follow 4600 children aged 2-15 years at enrollment, distributed in 50 clusters of 5 × 5 city blocks each. Clusters will be randomly allocated (n = 25 per arm) using covariate-constrained randomization. A "fried egg" design will be followed, in which all blocks of the 5 × 5 cluster receive the intervention, but all sampling to evaluate the epidemiological and entomological endpoints will occur in the "yolk," the center 3 × 3 city blocks of each cluster. TIRS will be implemented as a preventive application (~ 1-2 months prior to the beginning of the ABV season). Active monitoring for symptomatic ABV illness will occur through weekly household visits and enhanced surveillance. Annual sero-surveys will be performed after each transmission season and entomological evaluations of Ae. aegypti indoor abundance and ABV infection rates monthly during the period of active surveillance. Epidemiological and entomological evaluation will continue for up to three transmission seasons. DISCUSSION: The findings from this study will provide robust epidemiological evidence of the efficacy of TIRS in reducing ABV illness and infection. If efficacious, TIRS could drive a paradigm shift in Aedes control by considering Ae. aegypti behavior to guide residual insecticide applications and changing deployment to preemptive control (rather than in response to symptomatic cases), two major enhancements to existing practice. TRIAL REGISTRATION: ClinicalTrials.gov NCT04343521 . Registered on 13 April 2020. The protocol also complies with the WHO International Clinical Trials Registry Platform (ICTRP) (Additional file 1). PRIMARY SPONSOR: National Institutes of Health, National Institute of Allergy and Infectious Diseases (NIH/NIAID). |
High levels of HIV drug resistance among adults failing second-line antiretroviral therapy in Namibia.
Jordan MR , Hamunime N , Bikinesi L , Sawadogo S , Agolory S , Shiningavamwe AN , Negussie T , Fisher-Walker CL , Raizes EG , Mutenda N , Hunter CJ , Dean N , Steegen K , Kana V , Carmona S , Yang C , Tang AM , Parkin N , Hong SY . Medicine (Baltimore) 2020 99 (37) e21661 To support optimal third-line antiretroviral therapy (ART) selection in Namibia, we investigated the prevalence of HIV drug resistance (HIVDR) at time of failure of second-line ART. A cross-sectional study was conducted between August 2016 and February 2017. HIV-infected people ≥15 years of age with confirmed virological failure while receiving ritonavir-boosted protease inhibitor (PI/r)-based second-line ART were identified at 15 high-volume ART clinics representing over >70% of the total population receiving second-line ART. HIVDR genotyping of dried blood spots obtained from these individuals was performed using standard population sequencing methods. The Stanford HIVDR algorithm was used to identify sequences with predicted resistance; genotypic susceptibility scores for potential third-line regimens were calculated. Two hundred thirty-eight individuals were enrolled; 57.6% were female. The median age and duration on PI/r-based ART at time of enrolment were 37 years and 3.46 years, respectively. 97.5% received lopinavir/ritonavir-based regimens. The prevalence of nucleoside reverse transcriptase inhibitor (NRTI), non-nucleoside reverse transcriptase inhibitor (NNRTI), and PI/r resistance was 50.6%, 63.1%, and 13.1%, respectively. No significant association was observed between HIVDR prevalence and age or sex. This study demonstrates high levels of NRTI and NNRTI resistance and moderate levels of PI resistance in people receiving PI/r-based second-line ART in Namibia. Findings underscore the need for objective and inexpensive measures of adherence to identify those in need of intensive adherence counselling, routine viral load monitoring to promptly detect virological failure, and HIVDR genotyping to optimize selection of third-line drugs in Namibia. |
Factors associated with HIV testing among Atlanta's homeless youth
Myles RL , Best J , Bautista G , Wright ER , LaBoy A , Demissie Z , Dean HD . AIDS Educ Prev 2020 32 (4) 325-336 Homeless youth experience increased risk of contracting HIV, making HIV testing imperative in this population. We analyzed factors associated with HIV testing among homeless youth in Atlanta, Georgia using data from the 2015 Atlanta Youth Count and Needs Assessment. The analysis included 693 homeless youth aged 14-25 years, of whom 88.4% reported ever being tested for HIV, and 74.6% reported being tested within the previous year. Prevalence of ever testing for HIV was significantly higher among youth who reported risk factors for HIV (sexually active, transactional sex, or ever having an STI). Higher prevalence of testing within the last year was significantly associated with experiencing physical abuse or transactional sex. However, reporting ≥ 4 sexual partners or not using condoms were not associated with higher testing. Although testing prevalence among homeless youth was high, homeless youth engaging in certain high risk behaviors could benefit from further promotion of HIV testing. |
Policy and public health: Reducing the burden of infectious diseases
Burton DC , Burris S , Mermin JH , Purcell DW , Zeigler SC , Bull-Otterson L , Dean HD . Public Health Rep 2020 135 5s-9s The Centers for Disease Control and Prevention (CDC) works for a future free of HIV/AIDS, viral hepatitis, sexually transmitted diseases (STDs), and tuberculosis (TB). Policy can have powerful effects on the complex, multisectoral factors that influence the population-level morbidity, mortality, and health disparities of these and other diseases.1-4 Public health policy approaches comprise laws, regulations, incentive systems, or other standardized procedures and practices aimed at influencing institutional and individual behavior to improve health and health equity.5,6 Laws and policies that were not designed to achieve health-related objectives also can have important, albeit unintended, health effects. A systematic study of the association between policies and population health is needed to guide the development and implementation of health-promoting policy strategies that are feasible and effective and that minimize harms. This supplemental issue of Public Health Reports provides timely research on policy interventions that have the potential to reduce the incidence, morbidity, or mortality of HIV/AIDS, viral hepatitis, STDs, and TB. Furthermore, the articles in this supplement demonstrate a typology of public health law and policy research that supports vital and comprehensive examination of the evidence on which policy interventions can be based. We summarize the proposed research typology, apply it to the diversity of articles included in this supplement, and discuss future directions for this important field of research. |
Differential Association of HIV Funding With HIV Mortality by Race/Ethnicity, United States, 1999-2017.
Truman BI , Moonesinghe R , Brown YT , Chang MH , Mermin JH , Dean HD . Public Health Rep 2020 135 149s-157s OBJECTIVE: Federal funds have been spent to reduce the disproportionate effects of HIV/AIDS on racial/ethnic minority groups in the United States. We investigated the association between federal domestic HIV funding and age-adjusted HIV death rates by race/ethnicity in the United States during 1999-2017. METHODS: We analyzed HIV funding data from the Kaiser Family Foundation by federal fiscal year (FFY) and US age-adjusted death rates (AADRs) by race/ethnicity (Hispanic, non-Hispanic white, non-Hispanic black, and Asian/Pacific Islander and American Indian/Alaska Native [API+AI/AN]) from Centers for Disease Control and Prevention WONDER detailed mortality files. We fit joinpoint regression models to estimate the annual percentage change (APC), average APC, and changes in AADRs per billion US dollars in HIV funding, with 95% confidence intervals (CIs). For 19 data points, the number of joinpoints ranged from 0 to 4 on the basis of rules set by the program or by the user. A Monte Carlo permutation test indicated significant (P < .05) changes at joinpoints, and 2-sided t tests indicated significant APCs in AADRs. RESULTS: Domestic HIV funding increased from $10.7 billion in FFY 1999 to $26.3 billion in FFY 2017, but AADRs decreased at different rates for each racial/ethnic group. The average rate of change in AADR per US billion dollars was -9.4% (95% CI, -10.9% to -7.8%) for Hispanic residents, -7.8% (95% CI, -9.0% to -6.6%) for non-Hispanic black residents, -6.7% (95% CI, -9.3% to -4.0%) for non-Hispanic white residents, and -5.2% (95% CI, -7.8% to -2.5%) for non-Hispanic API+AI/AN residents. CONCLUSIONS: Increased domestic HIV funding was associated with faster decreases in age-adjusted HIV death rates for Hispanic and non-Hispanic black residents than for residents in other racial/ethnic groups. Increasing US HIV funding could be associated with decreasing future racial/ethnic disparities in the rate of HIV-related deaths. |
Characteristics of Persons Who Died with COVID-19 - United States, February 12-May 18, 2020.
Wortham JM , Lee JT , Althomsons S , Latash J , Davidson A , Guerra K , Murray K , McGibbon E , Pichardo C , Toro B , Li L , Paladini M , Eddy ML , Reilly KH , McHugh L , Thomas D , Tsai S , Ojo M , Rolland S , Bhat M , Hutchinson K , Sabel J , Eckel S , Collins J , Donovan C , Cope A , Kawasaki B , McLafferty S , Alden N , Herlihy R , Barbeau B , Dunn AC , Clark C , Pontones P , McLafferty ML , Sidelinger DE , Krueger A , Kollmann L , Larson L , Holzbauer S , Lynfield R , Westergaard R , Crawford R , Zhao L , Bressler JM , Read JS , Dunn J , Lewis A , Richardson G , Hand J , Sokol T , Adkins SH , Leitgeb B , Pindyck T , Eure T , Wong K , Datta D , Appiah GD , Brown J , Traxler R , Koumans EH , Reagan-Steiner S . MMWR Morb Mortal Wkly Rep 2020 69 (28) 923-929 During January 1, 2020-May 18, 2020, approximately 1.3 million cases of coronavirus disease 2019 (COVID-19) and 83,000 COVID-19-associated deaths were reported in the United States (1). Understanding the demographic and clinical characteristics of decedents could inform medical and public health interventions focused on preventing COVID-19-associated mortality. This report describes decedents with laboratory-confirmed infection with SARS-CoV-2, the virus that causes COVID-19, using data from 1) the standardized CDC case-report form (case-based surveillance) (https://www.cdc.gov/coronavirus/2019-ncov/php/reporting-pui.html) and 2) supplementary data (supplemental surveillance), such as underlying medical conditions and location of death, obtained through collaboration between CDC and 16 public health jurisdictions (15 states and New York City). |
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