Last data update: Sep 16, 2024. (Total: 47680 publications since 2009)
Records 1-30 (of 31 Records) |
Query Trace: Sheldon S [original query] |
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Metagenomic detection of bacterial zoonotic pathogens among febrile patients, Tanzania, 2007-2009
Rolfe RJ , Sheldon SW , Kingry LC , Petersen JM , Maro VP , Kinabo GD , Saganda W , Maze MJ , Halliday JEB , Nicholson WL , Galloway RL , Rubach MP , Crump JA . Emerg Infect Dis 2024 30 (8) 1599-1608 Bacterial zoonoses are established causes of severe febrile illness in East Africa. Within a fever etiology study, we applied a high-throughput 16S rRNA metagenomic assay validated for detecting bacterial zoonotic pathogens. We enrolled febrile patients admitted to 2 referral hospitals in Moshi, Tanzania, during September 2007-April 2009. Among 788 participants, median age was 20 (interquartile range 2-38) years. We performed PCR amplification of V1-V2 variable region 16S rRNA on cell pellet DNA, then metagenomic deep-sequencing and pathogenic taxonomic identification. We detected bacterial zoonotic pathogens in 10 (1.3%) samples: 3 with Rickettsia typhi, 1 R. conorii, 2 Bartonella quintana, 2 pathogenic Leptospira spp., and 1 Coxiella burnetii. One other sample had reads matching a Neoerhlichia spp. previously identified in a patient from South Africa. Our findings indicate that targeted 16S metagenomics can identify bacterial zoonotic pathogens causing severe febrile illness in humans, including potential novel agents. |
Challenges of COVID-19 case forecasting in the US, 2020-2021
Lopez VK , Cramer EY , Pagano R , Drake JM , O'Dea EB , Adee M , Ayer T , Chhatwal J , Dalgic OO , Ladd MA , Linas BP , Mueller PP , Xiao J , Bracher J , Castro Rivadeneira AJ , Gerding A , Gneiting T , Huang Y , Jayawardena D , Kanji AH , Le K , Mühlemann A , Niemi J , Ray EL , Stark A , Wang Y , Wattanachit N , Zorn MW , Pei S , Shaman J , Yamana TK , Tarasewicz SR , Wilson DJ , Baccam S , Gurung H , Stage S , Suchoski B , Gao L , Gu Z , Kim M , Li X , Wang G , Wang L , Wang Y , Yu S , Gardner L , Jindal S , Marshall M , Nixon K , Dent J , Hill AL , Kaminsky J , Lee EC , Lemaitre JC , Lessler J , Smith CP , Truelove S , Kinsey M , Mullany LC , Rainwater-Lovett K , Shin L , Tallaksen K , Wilson S , Karlen D , Castro L , Fairchild G , Michaud I , Osthus D , Bian J , Cao W , Gao Z , Lavista Ferres J , Li C , Liu TY , Xie X , Zhang S , Zheng S , Chinazzi M , Davis JT , Mu K , Pastore YPiontti A , Vespignani A , Xiong X , Walraven R , Chen J , Gu Q , Wang L , Xu P , Zhang W , Zou D , Gibson GC , Sheldon D , Srivastava A , Adiga A , Hurt B , Kaur G , Lewis B , Marathe M , Peddireddy AS , Porebski P , Venkatramanan S , Wang L , Prasad PV , Walker JW , Webber AE , Slayton RB , Biggerstaff M , Reich NG , Johansson MA . PLoS Comput Biol 2024 20 (5) e1011200 During the COVID-19 pandemic, forecasting COVID-19 trends to support planning and response was a priority for scientists and decision makers alike. In the United States, COVID-19 forecasting was coordinated by a large group of universities, companies, and government entities led by the Centers for Disease Control and Prevention and the US COVID-19 Forecast Hub (https://covid19forecasthub.org). We evaluated approximately 9.7 million forecasts of weekly state-level COVID-19 cases for predictions 1-4 weeks into the future submitted by 24 teams from August 2020 to December 2021. We assessed coverage of central prediction intervals and weighted interval scores (WIS), adjusting for missing forecasts relative to a baseline forecast, and used a Gaussian generalized estimating equation (GEE) model to evaluate differences in skill across epidemic phases that were defined by the effective reproduction number. Overall, we found high variation in skill across individual models, with ensemble-based forecasts outperforming other approaches. Forecast skill relative to the baseline was generally higher for larger jurisdictions (e.g., states compared to counties). Over time, forecasts generally performed worst in periods of rapid changes in reported cases (either in increasing or decreasing epidemic phases) with 95% prediction interval coverage dropping below 50% during the growth phases of the winter 2020, Delta, and Omicron waves. Ideally, case forecasts could serve as a leading indicator of changes in transmission dynamics. However, while most COVID-19 case forecasts outperformed a naïve baseline model, even the most accurate case forecasts were unreliable in key phases. Further research could improve forecasts of leading indicators, like COVID-19 cases, by leveraging additional real-time data, addressing performance across phases, improving the characterization of forecast confidence, and ensuring that forecasts were coherent across spatial scales. In the meantime, it is critical for forecast users to appreciate current limitations and use a broad set of indicators to inform pandemic-related decision making. |
Anaplasma bovis-Like Infections in humans, United States, 2015-2017
Karpathy SE , Kingry L , Pritt BS , Berry JC , Chilton NB , Dergousoff SJ , Cortinas R , Sheldon SW , Oatman S , Anacker M , Petersen J , Paddock CD . Emerg Infect Dis 2023 29 (9) 1904-1907 We detected the DNA of an Anaplasma bovis-like bacterium in blood specimens from 4 patients from the United States with suspected tickborne illnesses. Initial molecular characterization of this novel agent reveals identity to A. bovis-like bacteria detected in Dermacentor variabilis ticks collected from multiple US states. |
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 |
Development and validation of a real-time PCR test to detect Bartonella quintana in clinical samples
Choat J , Yockey B , Sheldon SW , Pappert R , Petersen J , Dietrich EA . Diagn Microbiol Infect Dis 2023 106 (4) 116000 This study reports on the validation of a real-time polymerase chain reaction test targeting the vomp region of Bartonella quintana. The assay displayed 100% sensitivity and specificity for the 52 bloods and 159 cultures tested. Molecular diagnosis of Bartonella quintana can aid clinical treatment during acute infection. |
RABIES DIAGNOSIS AND RESPONSE TO VACCINATION IN SOUTHERN TAMANDUA (TAMANDUA TETRADACTYLA).
Cushing AC , Sheldon J , Martinelli L , Grome H , Souza M , Dunn J , Craig LE , Carlson A , Niezgoda M , Satheshkumar PS , Wallace R . J Zoo Wildl Med 2023 53 (4) 797-800 Rabies has rarely been described in Xenarthra, and rabies vaccine response has not been documented. A southern tamandua (Tamandua tetradactyla) presented with nonspecific clinical signs and was euthanatized. Subsequently, immunohistochemistry and RT-PCR confirmed a rabies diagnosis. Following these tests, a group of eight captive tamanduas were vaccinated with a killed rabies vaccine, and titers were measured at the time of vaccination and 23 d later. One animal had day 0 titers suggestive of previous vaccination or exposure. All animals had detectable neutralizing rabies virus antibody titers after vaccination, but one animal failed to meet the World Organization for Animal Health's definition for adequate vaccination (≥0.5 IU/ml), and two other animals had low antibody titers (0.56 and 0.6 IU/ml). Rabies should be considered as a possible cause of illness in tamanduas, and rabies vaccination may be a useful preventative measure when anthropic interaction through medical care or ambassador roles is occurring. |
Household characteristics associated with surface contamination of SARS-CoV-2 and frequency of RT-PCR and viral culture positivity-California and Colorado, 2021.
Shragai T , Pratt C , Castro Georgi J , Donnelly MAP , Schwartz NG , Soto R , Chuey M , Chu VT , Marcenac P , Park GW , Ahmad A , Albanese B , Totten SE , Austin B , Bunkley P , Cherney B , Dietrich EA , Figueroa E , Folster JM , Godino C , Herzegh O , Lindell K , Relja B , Sheldon SW , Tong S , Vinjé J , Thornburg NJ , Matanock AM , Hughes LJ , Stringer G , Hudziec M , Beatty ME , Tate JE , Kirking HL , Hsu CH . PLoS One 2022 17 (10) e0274946 While risk of fomite transmission of SARS-CoV-2 is considered low, there is limited environmental data within households. This January-April 2021 investigation describes frequency and types of surfaces positive for SARS-CoV-2 by real-time reverse transcription polymerase chain reaction (RT-PCR) among residences with ≥1 SARS-CoV-2 infection, and associations of household characteristics with surface RT-PCR and viable virus positivity. Of 1232 samples from 124 households, 27.8% (n = 342) were RT-PCR positive with nightstands (44.1%) and pillows (40.9%) most frequently positive. SARS-CoV-2 lineage, documented household transmission, greater number of infected persons, shorter interval between illness onset and sampling, total household symptoms, proportion of infected persons ≤12 years old, and persons exhibiting upper respiratory symptoms or diarrhea were associated with more positive surfaces. Viable virus was isolated from 0.2% (n = 3 samples from one household) of all samples. This investigation suggests that while SARS-CoV-2 on surfaces is common, fomite transmission risk in households is low. |
SARS-CoV-2 infection risk among vaccinated and unvaccinated household members during the Alpha variant surge - Denver, Colorado, and San Diego, California, January-April 2021.
McCormick DW , Konkle SL , Magleby R , Chakrabarti AK , Cherney B , Lindell K , Namageyo-Funa A , Visser S , Soto RA , Donnelly MAP , Stringer G , Austin B , Beatty ME , Stous S , Albanese BA , Chu VT , Chuey M , Dietrich EA , Drobeniuc J , Folster JM , Killerby ME , Lehman JA , McDonald EC , Ruffin J , Schwartz NG , Sheldon SW , Sleweon S , Thornburg NJ , Hughes LJ , Petway M , Tong S , Whaley MJ , Kirking HL , Tate JE , Hsu CH , Matanock A . Vaccine 2022 40 (33) 4845-4855 BACKGROUND: COVID-19 vaccination reduces SARS-CoV-2 infection and transmission. However, evidence is emerging on the degree of protection across variants and in high-transmission settings. To better understand the protection afforded by vaccination specifically in a high-transmission setting, we examined household transmission of SARS-CoV-2 during a period of high community incidence with predominant SARS-CoV-2 B.1.1.7 (Alpha) variant, among vaccinated and unvaccinated contacts. METHODS: We conducted a household transmission investigation in San Diego County, California, and Denver, Colorado, during January-April 2021. Households were enrolled if they had at least one person with documented SARS-CoV-2 infection. We collected nasopharyngeal swabs, blood, demographic information, and vaccination history from all consenting household members. We compared infection risks (IRs), RT-PCR cycle threshold values, SARS-CoV-2 culture results, and antibody statuses among vaccinated and unvaccinated household contacts. RESULTS: We enrolled 493 individuals from 138 households. The SARS-CoV-2 variant was identified from 121/138 households (88%). The most common variants were Alpha (75/121, 62%) and Epsilon (19/121, 16%). There were no households with discordant lineages among household members. One fully vaccinated secondary case was symptomatic (13%); the other 5 were asymptomatic (87%). Among unvaccinated secondary cases, 105/108 (97%) were symptomatic. Among 127 households with a single primary case, the IR for household contacts was 45% (146/322; 95% Confidence Interval [CI] 40-51%). The observed IR was higher in unvaccinated (130/257, 49%, 95% CI 45-57%) than fully vaccinated contacts (6/26, 23%, 95% CI 11-42%). A lower proportion of households with a fully vaccinated primary case had secondary cases (1/5, 20%) than households with an unvaccinated primary case (66/108, 62%). CONCLUSIONS: Although SARS-CoV-2 infections in vaccinated household contacts were reported in this high transmission setting, full vaccination protected against SARS-CoV-2 infection. These findings further support the protective effect of COVID-19 vaccination and highlight the need for ongoing vaccination among eligible persons. |
Comparison of Home Antigen Testing With RT-PCR and Viral Culture During the Course of SARS-CoV-2 Infection.
Chu VT , Schwartz NG , Donnelly MAP , Chuey MR , Soto R , Yousaf AR , Schmitt-Matzen EN , Sleweon S , Ruffin J , Thornburg N , Harcourt JL , Tamin A , Kim G , Folster JM , Hughes LJ , Tong S , Stringer G , Albanese BA , Totten SE , Hudziec MM , Matzinger SR , Dietrich EA , Sheldon SW , Stous S , McDonald EC , Austin B , Beatty ME , Staples JE , Killerby ME , Hsu CH , Tate JE , Kirking HL , Matanock A . JAMA Intern Med 2022 182 (7) 701-709 IMPORTANCE: As self-collected home antigen tests become widely available, a better understanding of their performance during the course of SARS-CoV-2 infection is needed. OBJECTIVE: To evaluate the diagnostic performance of home antigen tests compared with reverse transcription-polymerase chain reaction (RT-PCR) and viral culture by days from illness onset, as well as user acceptability. DESIGN, SETTING, AND PARTICIPANTS: This prospective cohort study was conducted from January to May 2021 in San Diego County, California, and metropolitan Denver, Colorado. The convenience sample included adults and children with RT-PCR-confirmed infection who used self-collected home antigen tests for 15 days and underwent at least 1 nasopharyngeal swab for RT-PCR, viral culture, and sequencing. EXPOSURES: SARS-CoV-2 infection. MAIN OUTCOMES AND MEASURES: The primary outcome was the daily sensitivity of home antigen tests to detect RT-PCR-confirmed cases. Secondary outcomes included the daily percentage of antigen test, RT-PCR, and viral culture results that were positive, and antigen test sensitivity compared with same-day RT-PCR and cultures. Antigen test use errors and acceptability were assessed for a subset of participants. RESULTS: This study enrolled 225 persons with RT-PCR-confirmed infection (median [range] age, 29 [1-83] years; 117 female participants [52%]; 10 [4%] Asian, 6 [3%] Black or African American, 50 [22%] Hispanic or Latino, 3 [1%] Native Hawaiian or Other Pacific Islander, 145 [64%] White, and 11 [5%] multiracial individuals) who completed 3044 antigen tests and 642 nasopharyngeal swabs. Antigen test sensitivity was 50% (95% CI, 45%-55%) during the infectious period, 64% (95% CI, 56%-70%) compared with same-day RT-PCR, and 84% (95% CI, 75%-90%) compared with same-day cultures. Antigen test sensitivity peaked 4 days after illness onset at 77% (95% CI, 69%-83%). Antigen test sensitivity improved with a second antigen test 1 to 2 days later, particularly early in the infection. Six days after illness onset, antigen test result positivity was 61% (95% CI, 53%-68%). Almost all (216 [96%]) surveyed individuals reported that they would be more likely to get tested for SARS-CoV-2 infection if home antigen tests were available over the counter. CONCLUSIONS AND RELEVANCE: The results of this cohort study of home antigen tests suggest that sensitivity for SARS-CoV-2 was moderate compared with RT-PCR and high compared with viral culture. The results also suggest that symptomatic individuals with an initial negative home antigen test result for SARS-CoV-2 infection should test again 1 to 2 days later because test sensitivity peaked several days after illness onset and improved with repeated testing. |
Evaluation of individual and ensemble probabilistic forecasts of COVID-19 mortality in the United States.
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 . Proc Natl Acad Sci U S A 2022 119 (15) e2113561119 SignificanceThis paper compares the probabilistic accuracy of short-term forecasts of reported deaths due to COVID-19 during the first year and a half of the pandemic in the United States. Results show high variation in accuracy between and within stand-alone models and more consistent accuracy from an ensemble model that combined forecasts from all eligible models. This demonstrates that an ensemble model provided a reliable and comparatively accurate means of forecasting deaths during the COVID-19 pandemic that exceeded the performance of all of the models that contributed to it. This work strengthens the evidence base for synthesizing multiple models to support public-health action. |
Household transmission of SARS-CoV-2 Alpha variant - United States, 2021.
Donnelly MAP , Chuey MR , Soto R , Schwartz NG , Chu VT , Konkle SL , Sleweon S , Ruffin J , Haberling DL , Guagliardo SAJ , Stoddard RA , Anderson RD , Morgan CN , Rossetti R , McCormick DW , Magleby R , Sheldon SW , Dietrich EA , Uehara A , Retchless AC , Tong S , Folster JM , Drobeniuc J , Petway ME , Austin B , Stous S , McDonald E , Jain S , Hudziec MM , Stringer G , Albanese BA , Totten SE , Staples JE , Killerby ME , Hughes L , Matanock A , Beatty M , Tate JE , Kirking HL , Hsu CH . Clin Infect Dis 2022 75 (1) e122-e132 BACKGROUND: In Spring 2021, SARS-CoV-2 B.1.1.7 (Alpha) became the predominant variant in the U.S. Research suggests that Alpha has increased transmissibility compared to non-Alpha lineages. We estimated household secondary infection risk (SIR), assessed characteristics associated with transmission, and compared symptoms of persons with Alpha and non-Alpha infections. METHODS: We followed households with SARS-CoV-2 infection for two weeks in San Diego County and metropolitan Denver, January to April 2021. We collected epidemiologic information and biospecimens for serology, RT-PCR, and whole genome sequencing. We stratified SIR and symptoms by lineage, and identified characteristics associated with transmission using Generalized Estimating Equations. RESULTS: We investigated 127 households with 322 household contacts; 72 households (56.7%) had member(s) with secondary infections. SIRs were not significantly higher for Alpha (61.0% [95% confidence interval (CI) 52.4-69.0%]) than non-Alpha (55.6% [CI 44.7-65.9%], P = 0.49). In households with Alpha, persons who identified as Asian or Hispanic/Latino had significantly higher SIRs than those who identified as White (P = 0.01 and 0.03, respectively). Close contact (e.g., kissing, hugging) with primary cases was associated with increased transmission for all lineages. Persons with Alpha infection were more likely to report constitutional symptoms than persons with non-Alpha (86.9% vs. 76.8%, P = 0.05). CONCLUSIONS: Household SIRs were similar for Alpha and non-Alpha. Comparable SIRs may be due to saturation of transmission risk in households owing to extensive close contact, or true lack of difference in transmission rates. Avoiding close contact within households may reduce SARS-CoV-2 transmission for all lineages among household members. |
Simultaneous detection and differentiation of clinically relevant relapsing fever
Dietrich EA , Replogle AJ , Sheldon SW , Petersen JM . J Clin Microbiol 2021 59 (7) e0298120 Bacterial vector-borne diseases, including Borrelia species, present a significant diagnostic, clinical, and public health challenge due to their overlapping symptoms and the breadth of causative agents and arthropod vectors. The relapsing fever (RF) borreliae encompass both established and emerging pathogens and are transmitted to humans by soft ticks, hard ticks, or lice. We developed a real-time semi-multiplex PCR assay that detects multiple RF borreliae causing human illness and classifies them into one of three groups. The groups are based on genetic similarity and include agents of soft-tick relapsing fever (B. hermsii and others), the emerging hard tick transmitted pathogen B. miyamotoi, and the agent of louse-borne relapsing fever (B. recurrentis) The real-time PCR assay uses a single primer pair designed to amplify all known pathogenic RF borreliae, and multiple TaqMan probes to allow for detection of and differentiation among the three groups. The assay detects all RF borreliae tested with an analytical limit of detection below 15 genome equivalents per reaction. Thirty isolates of RF borreliae encompassing six species were accurately identified. Thirty-nine of 41 residual specimens (EDTA whole blood, serum, or plasma) from patients with RF were detected and correctly classified. None of 42 clinical samples from patients with other infections and 46 culture specimens from non-RF bacteria were detected. The development of a single assay real-time PCR approach will help to improve diagnosis of RF by simplifying the selection of tests to aid in clinical management of acutely ill RF patients. |
Detection of Tick-borne Bacteria from Whole Blood Using 16S Ribosomal RNA Gene PCR Followed by Next-Generation Sequencing.
Rodino KG , Wolf MJ , Sheldon S , Kingry LC , Petersen JM , Patel R , Pritt BS . J Clin Microbiol 2021 59 (5) Reported cases of tick-borne diseases have steadily increased for more than a decade. In the United States, a majority of tick-borne infections are caused by bacteria. Clinical diagnosis may be challenging as tick-borne diseases can present with similar symptoms. Laboratory diagnosis has historically relied on serologic methods, which have limited utility during the acute phase of disease. Pathogen-specific molecular methods have improved early diagnosis, but can be expensive when bundled together and miss unexpected or novel pathogens. To address these shortcomings, we developed a 16S ribosomal RNA (rRNA) gene PCR with next-generation sequencing approach to detect tick-borne bacteria in whole blood. A workflow was optimized by comparing combinations of two extractions platforms and two primer sets, ultimately pursuing DNA extraction from blood with the MagNA Pure 96 and PCR amplification using dual-priming oligonucleotide primers specific to the V1-V3 region of the 16S rRNA gene. The amplified product underwent modified Illumina 16S metagenomics sequencing library preparation and sequencing on a MiSeq V2 Nano flow cell, with data analysis using Pathogenomix RipSeq NGS software. Results with the developed method were compared to those from a V1-V2 16S rRNA gene primer set described by the Centers for Disease Control and Prevention (CDC). The V1-V3 assay demonstrated equivalent performance to the CDC assay, with each method showing concordance with targeted PCR results in 31 of 32 samples, and detecting 22 of 23 expected organisms. These data demonstrate the potential for using a broad-range bacterial detection approach for diagnosis of tick-borne bacterial infection from blood. |
COVID-19-Related Hospitalization Rates and Severe Outcomes Among Veterans From 5 Veterans Affairs Medical Centers: Hospital-Based Surveillance Study.
Cardemil CV , Dahl R , Prill MM , Cates J , Brown S , Perea A , Marconi V , Bell L , Rodriguez-Barradas M , Rivera-Dominguez G , Beenhouwer D , Poteshkina A , Holodniy M , Lucero-Obusan C , Balachandran N , Hall AJ , Kim L , Langley G . JMIR Public Health Surveill 2020 7 (1) e24502 BACKGROUND: COVID-19 has disproportionately affected older adults and certain racial and ethnic groups in the US. Data quantifying the disease burden, as well as describing clinical outcomes during hospitalization among these groups, is needed. OBJECTIVE: We aimed to describe interim COVID-19 hospitalization rates and severe clinical outcomes by age group and race and ethnicity among Veterans in a multi-site surveillance network. METHODS: We implemented a multisite COVID-19 surveillance platform in 5 Veterans Affairs Medical Centers (VAMCs: Atlanta, Bronx, Houston, Palo Alto, and Los Angeles), collectively serving >396,000 patients annually. From February 27- July 17 2020, we actively identified SARS-CoV-2 positive inpatient cases through screening of admitted patients and review of laboratory test results. We manually abstracted medical charts for demographics, underlying medical conditions, and clinical outcomes of COVID-19 hospitalized patients. We calculated hospitalization incidence and incidence rate ratios, and relative risk (RR) for invasive mechanical ventilation, intensive care unit (ICU) admission, and death after adjusting for age, race and ethnicity, and underlying medical conditions. RESULTS: We identified 621 laboratory-confirmed hospitalized COVID-19 cases. Median age was 70 years, 66% were aged ≥65 years, and 94% were male. Most COVID-19 diagnoses were among non-Hispanic Blacks (52%), followed by non-Hispanic Whites (25%) and Hispanic or Latinos (18%). Hospitalization rates were highest among Veterans aged ≥85 years, Hispanic or Latino, and non-Hispanic Black (430, 317 and 298 per 100,000, respectively); Veterans aged ≥85 years had a 14-fold increased rate of hospitalization compared with Veterans aged 18-29 years (95% CI: 5.7-34.6), while Hispanic or Latino and Black Veterans had a 4.6 and 4.2-fold increased rate of hospitalization compared with non-Hispanic White Veterans (95% CI: 3.6-5.9), respectively. Overall, 11.6% of patients required invasive mechanical ventilation, 26.6% were admitted to the intensive care unit (ICU), and 16.9% died in hospital. The adjusted RR for invasive mechanical ventilation and ICU admission did not differ by age group or race/ethnicity, but Veterans aged ≥65 had a 4.5-fold increased risk of death while hospitalized with COVID-19 compared with those aged <65 years (95% CI: 2.4-8.6). CONCLUSIONS: COVID-19 surveillance at 5 VAMCs across the US demonstrated higher hospitalization rates and severe outcomes in older Veterans, and higher hospitalization rates in Hispanic or Latino and non-Hispanic Black Veterans compared to non-Hispanic White Veterans. These data highlight the need for targeted prevention and timely treatment for Veterans, with special attention to increasing age, Hispanic or Latino and non-Hispanic Black Veterans. |
Do I Have HIV or Not? Lack of RNA Detection and the Case for Sensitive DNA Testing.
Springer SA , Masciotra S , Johnson JA , Campbell S . Open Forum Infect Dis 2020 7 (11) ofaa478 We present a case of a 20-year-old male who had ambiguous HIV test results after entering new provider care and whose status was later complicated by undetectable viral RNA off antiretroviral therapy (ART). Verifying HIV infection status may occasionally require sensitive DNA testing that might need to be considered in diagnostic guidelines to resolve diagnosis and ensure appropriate ART management. |
Childhood obesity evidence base project: A systematic review and meta-analysis of a new taxonomy of intervention components to improve weight status in children 2-5 years of age, 2005-2019
Scott-Sheldon LAJ , Hedges LV , Cyr C , Young-Hyman D , Khan LK , Magnus M , King H , Arteaga S , Cawley J , Economos CD , Haire-Joshu D , Hunter CM , Lee BY , Kumanyika SK , Ritchie LD , Robinson TN , Schwartz MB . Child Obes 2020 16 S221-s248 Objective: To evaluate the efficacy of childhood obesity interventions and conduct a taxonomy of intervention components that are most effective in changing obesity-related health outcomes in children 2-5 years of age. Methods: Comprehensive searches located 51 studies from 18,335 unique records. Eligible studies: (1) assessed children aged 2-5, living in the United States; (2) evaluated an intervention to improve weight status; (3) identified a same-aged comparison group; (4) measured BMI; and (5) were available between January 2005 and August 2019. Coders extracted study, sample, and intervention characteristics. Effect sizes [ESs; and 95% confidence intervals (CIs)] were calculated by using random-effects models. Meta-regression was used to determine which intervention components explain variability in ESs. Results: Included were 51 studies evaluating 58 interventions (N = 29,085; mean age = 4 years; 50% girls). Relative to controls, children receiving an intervention had a lower BMI at the end of the intervention (g = 0.10, 95% CI = 0.02-0.18; k = 55) and at the last follow-up (g = 0.17, 95% CI = 0.04-0.30; k = 14; range = 18-143 weeks). Three intervention components moderated efficacy: engage caregivers in praise/encouragement for positive health-related behavior; provide education about the importance of screen time reduction to caregivers; and engage pediatricians/health care providers. Conclusions: Early childhood obesity interventions are effective in reducing BMI in preschool children. Our findings suggest that facilitating caregiver education about the importance of screen time reduction may be an important strategy in reducing early childhood obesity. |
Childhood obesity evidence base project: A rationale for taxonomic versus conventional meta-analysis
Hedges LV , Saul JA , Cyr C , Magnus M , Scott-Sheldon LAJ , Young-Hyman D , Khan LK . Child Obes 2020 16 S21-s26 Introduction: There is a great need for analytic techniques that allow for the synthesis of learning across seemingly idiosyncratic interventions. Objectives: The primary objective of this paper is to introduce taxonomic meta-analysis and explain how it is different from conventional meta-analysis. Results: Conventional meta-analysis has previously been used to examine the effectiveness of childhood obesity prevention interventions. However, these tend to examine narrowly defined sections of obesity prevention initiatives, and as such, do not allow the field to draw conclusions across settings, participants, or subjects. Compared with conventional meta-analysis, taxonomic meta-analysis widens the aperture of what can be examined to synthesize evidence across interventions with diverse topics, goals, research designs, and settings. A component approach is employed to examine interventions at the level of their essential features or activities to identify the concrete aspects of interventions that are used (intervention components), characteristics of the intended populations (target population or intended recipient characteristics), and facets of the environments in which they operate (contextual elements), and the relationship of these components to effect size. In addition, compared with conventional meta-analysis methods, taxonomic meta-analyses can include the results of natural experiments, policy initiatives, program implementation efforts and highly controlled experiments (as examples) regardless of the design of the report being analyzed as long as the intended outcome is the same. It also characterizes the domain of interventions that have been studied. Conclusion: Taxonomic meta-analysis can be a powerful tool for summarizing the evidence that exists and for generating hypotheses that are worthy of more rigorous testing. |
Childhood obesity evidence base project: Methods for taxonomy development for application in taxonomic meta-analysis
King H , Magnus M , Hedges LV , Cyr C , Young-Hyman D , Kettel Khan L , Scott-Sheldon LAJ , Saul JA , Arteaga S , Cawley J , Economos CD , Haire-Joshu D , Hunter CM , Lee BY , Kumanyika SK , Ritchie LD , Robinson TN , Schwartz MB . Child Obes 2020 16 S27-s220 Meta-analysis has been used to examine the effectiveness of childhood obesity prevention efforts, yet traditional conventional meta-analytic methods restrict the kinds of studies included, and either narrowly define mechanisms and agents of change, or examine the effectiveness of whole interventions as opposed to the specific actions that comprise interventions. Taxonomic meta-analytic methods widen the aperture of what can be included in a meta-analysis data set, allowing for inclusion of many types of interventions and study designs. The National Collaborative on Childhood Obesity Research Childhood Obesity Evidence Base (COEB) project focuses on interventions intended to prevent childhood obesity in children 2-5 years old who have an outcome measure of BMI. The COEB created taxonomies, anchored in the Social Ecological Model, which catalog specific outcomes, intervention components, intended recipients, and contexts of policies, initiatives, and interventions conducted at the individual, interpersonal, organizational, community, and societal level. Taxonomies were created by discovery from the literature itself using grounded theory. This article describes the process used for a novel taxonomic meta-analysis of childhood obesity prevention studies between the years 2010 and 2019. This method can be applied to other areas of research, including obesity prevention in additional populations. |
Targeted metagenomics for clinical detection and discovery of bacterial tickborne pathogens
Kingry L , Sheldon S , Oatman S , Pritt B , Anacker M , Bjork J , Neitzel D , Strain A , Berry J , Sloan L , Respicio-Kingry L , Dietrich E , Bloch K , Moncayo A , Srinivasamoorthy G , Hu B , Hinckley A , Mead P , Kugeler K , Petersen J . J Clin Microbiol 2020 58 (11) Tickborne diseases, due to a diversity of bacterial pathogens, represent a significant and increasing public health threat throughout the northern hemisphere. A high-throughput 16S V1-V2 rDNA-based metagenomics assay was developed and evaluated using >13,000 residual samples from patients suspected of tickborne illness and >1000 controls. Taxonomic predictions for tickborne bacteria were exceptionally accurate, as independently validated by secondary testing. Overall, 881 specimens were positive for bacterial tickborne agents. Twelve tickborne bacterial species were detected, including two novel pathogens, representing a 100% increase in the number of tickborne bacteria identified compared to what was possible by initial PCR testing. In three blood specimens, two tickborne bacteria were simultaneously detected. Seven bacteria, not known to be tick-transmitted, were also confirmed unique to samples from persons suspected of tickborne illness. These results indicate 16S V1-V2 metagenomics can greatly simplify diagnosis and accelerate discovery of bacterial tickborne pathogens. |
Incidence, etiology, and severity of acute gastroenteritis among prospectively enrolled patients in 4 Veterans Affairs hospitals and outpatient centers, 2016-18.
Cardemil CV , Balachandran N , Kambhampati A , Grytdal S , Dahl RM , Rodriguez-Barradas MC , Vargas B , Beenhouwer DO , Evangelista KV , Marconi VC , Meagley KL , Brown ST , Perea A , Lucero-Obusan C , Holodniy M , Browne H , Gautam R , Bowen MD , Vinje J , Parashar UD , Hall AJ . Clin Infect Dis 2020 73 (9) e2729-e2738 BACKGROUND: Acute gastroenteritis (AGE) burden, etiology, and severity in adults is not well-characterized. We implemented a multisite AGE surveillance platform in 4 Veterans Affairs Medical Centers (Atlanta, Bronx, Houston and Los Angeles), collectively serving >320,000 patients annually. METHODS: From July 1, 2016-June 30, 2018, we actively identified AGE inpatient cases and non-AGE inpatient controls through prospective screening of admitted patients and passively identified outpatient cases through stool samples submitted for clinical diagnostics. We abstracted medical charts and tested stool samples for 22 pathogens via multiplex gastrointestinal PCR panel followed by genotyping of norovirus- and rotavirus-positive samples. We determined pathogen-specific prevalence, incidence, and modified Vesikari severity scores. RESULTS: We enrolled 724 inpatient cases, 394 controls, and 506 outpatient cases. Clostridioides difficile and norovirus were most frequently detected among inpatients (cases vs controls: C. difficile, 18.8% vs 8.4%; norovirus, 5.1% vs 1.5%; p<0.01 for both) and outpatients (norovirus: 10.7%; C. difficile: 10.5%). Incidence per 100,000 population was highest among outpatients (AGE: 2715; C. difficile: 285; norovirus: 291) and inpatients >/=65 years old (AGE: 459; C. difficile: 91; norovirus: 26). Clinical severity scores were highest for inpatient norovirus, rotavirus, and Shigella/EIEC cases. Overall, 12% of AGE inpatient cases had ICU stays and 2% died; 3 deaths were associated with C. difficile and 1 with norovirus. C. difficile and norovirus were detected year-round with a fall/winter predominance. CONCLUSIONS: C. difficile and norovirus were leading AGE pathogens in outpatient and hospitalized US Veterans, resulting in severe disease. Clinicians should remain vigilant for bacterial and viral causes of AGE year-round. |
Trends in state policy support for sexual minorities and HIV-related outcomes among men who have sex with men in the United States, 2008-2014
Hatzenbuehler ML , McKetta S , Goldberg N , Sheldon A , Friedman SR , Cooper HL , Beane S , Williams LD , Tempalski B , Smith JC , Ibragimov U , Mermin J , Stall R . J Acquir Immune Defic Syndr 2020 85 (1) 39-45 BACKGROUND: To examine trends in state-level policy support for sexual minorities and HIV outcomes among MSM. METHODS: This longitudinal analysis linked state-level policy support for sexual minorities (N=94 Metropolitan Statistical Areas [MSAs] in 38 states) to 7 years of data (2008-2014) from CDC on HIV outcomes among MSM. Using latent growth mixture modeling, we combined 11 state-level policies (e.g., non-discrimination laws including sexual orientation as a protected class) from 1999-2014, deriving 3 latent groups: consistently low policy support; consistently high policy support; and increasing trajectory of policy support. Outcomes were HIV diagnoses per 10,000 MSM; late diagnoses (number of deaths within 12 months of HIV diagnosis and AIDS diagnoses within three months of HIV diagnosis) per 10,000 MSM; AIDS diagnoses per 10,000 MSM with HIV; and AIDS-related mortality per 10,000 MSM with AIDS. RESULTS: Compared to MSAs in states with low levels and increasing policy support for sexual minorities, MSAs in states with the highest level of policy support had lower risks of HIV diagnoses (Risk Difference [RD]=-37.9, 95% Confidence Interval [CI]: -54.7, -21.0), late diagnoses (RD=-12.5, 95% CI: -20.4, -4.7), and AIDS-related mortality (RD=-33.7, 95% CI: -61.2, -6.2), controlling for time and 7 MSA-level covariates. In low policy support states, 27% of HIV diagnoses, 21% of late diagnoses, and 10% of AIDS deaths among MSM were attributable to policy climate. CONCLUSION: State-level policy climate related to sexual minorities was associated with HIV health outcomes among MSM and could be a potential public health tool for HIV prevention and care. |
Establishing effective patient navigation programs in oncology
Lopez D , Pratt-Chapman ML , Rohan EA , Sheldon LK , Basen-Engquist K , Kline R , Shulman LN , Flores EJ . Support Care Cancer 2019 27 (6) 1985-1996 PURPOSE: Recent advances in cancer treatment have resulted in greatly improved survival, and yet many patients in the USA have not benefited due to poor access to healthcare and difficulty accessing timely care across the cancer care continuum. Recognizing these issues and the need to facilitate discussions on how to improve navigation services for patients with cancer, the National Cancer Policy Forum of the National Academies of Sciences, Engineering, and Medicine (NASEM) held a workshop entitled, "Establishing Effective Patient Navigation Programs in Oncology. The purpose of this manuscript is to disseminate the conclusions of this workshop while providing a clinically relevant review of patient navigation in oncology. DESIGN: Narrative literature review and summary of workshop discussions RESULTS: Patient navigation has been shown to be effective at improving outcomes throughout the spectrum of cancer care. Work remains to develop consensus on scope of practice and evaluation criteria and to align payment incentives and policy. CONCLUSION: Patient navigation plays an essential role in overcoming patient- and system-level barriers to improve access to cancer care and outcomes for those most in need. |
Antimicrobial Resistance in Neisseria gonorrhoeae: Proceedings of the STAR Sexually Transmitted Infection-Clinical Trial Group Programmatic Meeting.
Cristillo AD , Bristow CC , Torrone E , Dillon JA , Kirkcaldy RD , Dong H , Grad YH , Nicholas RA , Rice PA , Lawrence K , Oldach D , Shafer WM , Zhou P , Wi TE , Morris SR , Klausner JD . Sex Transm Dis 2018 46 (3) e18-e25 The goal of the Sexually Transmitted Infection Clinical Trial Group's (STI-CTG) Antimicrobial Resistance (AMR) in Neisseria gonorrhoeae (NG) meeting was to assemble experts from academia, government, non-profit and industry to discuss the current state of research, gaps and challenges in research and technology as well as priorities and new directions to address the continued emergence of multi-drug resistant NG infections. Topics discussed at the meeting, that will be the focus of this article, include AMR NG global surveillance initiatives, the use of whole genome sequencing (WGS) and bioinformatics to understand mutations associated with AMR, mechanisms of AMR, and novel antibiotics, vaccines and other methods to treat AMR NG. Key points highlighted during the meeting include: (i) US and International surveillance programs to understand AMR in NG. (ii) The US National Strategy for combating antimicrobial resistant bacteria. (iii) Surveillance needs, challenges and novel technologies. (iv) Plasmid- and chromosomally-mediated mechanisms of AMR in NG, (v) Novel therapeutic (e.g., sialic acid analogs, FH/Fc fusion molecule, monoclonal antibodies, topoisomerase inhibitors, fluoroketolides, LpxC inhibitors) and preventative (e.g., peptide mimic) strategies to combat infection. The way forward will require renewed political will, new funding initiatives and collaborations across academic and commercial research and public health programs. |
Surveillance for and Discovery of Borrelia Species in US Patients Suspected of Tickborne Illness.
Kingry LC , Anacker M , Pritt B , Bjork J , Respicio-Kingry L , Liu G , Sheldon S , Boxrud D , Strain A , Oatman S , Berry J , Sloan L , Mead P , Neitzel D , Kugeler KJ , Petersen JM . Clin Infect Dis 2017 66 (12) 1864-1871 Background: Tick-transmitted Borrelia species fall into two heterogeneous bacterial complexes comprised of multiple species, the relapsing fever (RF) group and the Borrelia burgdorferi sensu lato group, which are the causative agents of Lyme borreliosis (LB), the most common tickborne disease in the northern hemisphere. Geographic expansion of human LB in the United States and discovery of emerging Borrelia pathogens underscores the importance of surveillance for disease causing Borrelia. Methods: De-identified clinical specimens, submitted by providers throughout the United States, for patients suspected of LB, anaplasmosis, ehrlichiosis, or babesiosis, were screened using a Borrelia genus level TaqMan PCR. Borrelia species and sequence types (STs) were characterized by multi-locus sequence typing (MLST) utilizing next generation sequencing. Results: Among the 7,292 tested specimens tested, five different Borrelia species were identified: two causing LB, B. burgdorferi (n=25) and B. mayonii (n=9), and three RF borreliae, B. hermsii (n=1), B. miyamotoi (n=8), and CandidatusB. johnsonii (n=1), a species previously detected only in the bat tick, Carios kelleyi. ST diversity was greatest for B. burgdorferi positive specimens, with new STs identified primarily among synovial fluids. Conclusion: These results demonstrate broad PCR screening followed by MLST is a powerful surveillance tool for uncovering the spectrum of Borrelia species causing human disease, improving understanding of their geographic distribution, and investigating the correlation between B. burgdorferi STs and joint involvement. Detection of CandidatusB. johnsonii in a patient with suspected tickborne disease suggests this species may be a previously undetected cause of illness in humans with exposure to bat ticks. |
A molecular algorithm to detect and differentiate human pathogens infecting Ixodes scapularis and Ixodes pacificus (Acari: Ixodidae).
Graham CB , Maes SE , Hojgaard A , Fleshman AC , Sheldon SW , Eisen RJ . Ticks Tick Borne Dis 2017 9 (2) 390-403 The incidence and geographic range of tick-borne illness associated with Ixodes scapularis and Ixodes pacificus have dramatically increased in recent decades. Anaplasmosis, babesiosis, and Borrelia spirochete infections, including Lyme borreliosis, account for tens of thousands of reported cases of tick-borne disease every year. Assays that reliably detect pathogens in ticks allow investigators and public health agencies to estimate the geographic distribution of human pathogens, assess geographic variation in their prevalence, and evaluate the effectiveness of prevention strategies. As investigators continue to describe new species within the Borrelia burgdorferi sensu lato complex and to recognize some Ixodes-borne Borrelia species as human pathogens, assays are needed to detect and differentiate these species. Here we describe an algorithm to detect and differentiate pathogens in unfed I. scapularis and I. pacificus nymphs including Anaplasma phagocytophilum, Babesia microti, Borrelia burgdorferi sensu stricto, Borrelia mayonii, and Borrelia miyamotoi. The algorithm comprises 5 TaqMan real-time polymerase chain reaction assays and 3 sequencing protocols. It employs multiple targets for each pathogen to optimize specificity, a gene target for I. scapularis and I. pacificus to verify tick-derived DNA quality, and a pan-Borrelia target to detect Borrelia species that may emerge as human disease agents in the future. We assess the algorithm's sensitivity, specificity, and performance on field-collected ticks. |
A call for coordinated and evidence-based action to protect children outside of family care
Clay R , CdeBaca L , De Cock KM , Goosby E , Guttmacher A , Jacobs S , Pablos-Mendez A , Polaski S , Sheldon G , Steinberg D . Lancet 2012 379 (9811) e6-8 A caring and protective family, immediate and extended, is central to effective child protection. Children in the most dire straits, however, live without protective family care. These children may be found living on the streets or in institutions, trafficked, participating in armed groups, or exploited for their labour. Children in such circumstances often experience abuse, neglect, lack of stimulation, and extreme and toxic stress, all of which have a profoundly negative effect on a child's development and adult outcomes.1 | Children living outside of family care have largely fallen off the statistical map. There are only limited data about how many children live in such precarious circumstances, except for scattered estimates from some specific countries. Such children are often not covered in household-based surveys. Some international data collection activities provide useful information about these children, including USAID's Demographic and Health Surveys,2 UNICEF's Multiple Indicator Cluster Surveys,3 the Statistical Information and Monitoring Program on Child Labor surveys sponsored by the International Labour Organization,4 and the US Centers for Disease Control and Prevention's Violence Against Children surveys.5 Although there is a need for more evidence-based research, rough global estimates indicate that 17 800 000 children have lost both parents;6 2 000 000 children are in institutional care;7 1 800 000 children are victims of sex trafficking or involvement in pornography;8 and 1 100 000 children are trafficked for forced labour.9 |
Transmission efficiency of Francisella tularensis by adult American dog ticks (Acari: Ixodidae)
Reese SM , Petersen JM , Sheldon SW , Dolan MC , Dietrich G , Piesman J , Eisen RJ . J Med Entomol 2011 48 (4) 884-890 The American dog tick, Dermacentor variabilis (Say) (Acari: Ixodidae), has been implicated as a potential bridging vector to humans of Francisella tularensis, the etiological agent of tularemia. Since the initial studies evaluating vector competency of D. variabilis were conducted, F. tularensis has been subdivided into subspecies and clades that differ in their geographical distribution in the United States and in the severity of infections caused in humans. Here, we demonstrate that D. variabilis nymphs efficiently acquire, transtadially maintain, and transmit each of the strains tested (clades A1b and A2, and type B). Transmission efficiency by adult females was similarly high among infection groups and ranged from 58% for type B to 89% for A2 infections. In addition, we demonstrated that transmission can occur shortly after tick attachment. These findings support the concept that D. variabilis adults may play a significant role in epizootic transmission of F. tularensis, and as a bridging vector to humans. |
Assessing the quantitative relationships between preschool children's exposures to bisphenol A by route and urinary biomonitoring
Morgan MK , Jones PA , Calafat AM , Ye X , Croghan CW , Chuang JC , Wilson NK , Clifton MS , Figueroa Z , Sheldon LS . Environ Sci Technol 2011 45 (12) 5309-16 Limited published information exists on young children's exposures to bisphenol A (BPA) in the United States using urinary biomonitoring. In a previous project, we quantified the aggregate exposures of 257 preschool children to BPA in environmental and personal media over 48-h periods in 2000-2001 at homes and daycares in North Carolina and Ohio. In the present study for 81 Ohio preschool children ages 23-64 months, we quantified the children's urinary total BPA (free and conjugated) concentrations over these same 48-h periods in 2001. Then, we examined the quantitative relationships between the children's intakes doses of BPA through the dietary ingestion, nondietary ingestion, and inhalation routes and their excreted amounts of urinary BPA. BPA was detected in 100% of the urine samples. The estimated median intake doses of BPA for these 81 children were 109 ng/kg/day (dietary ingestion), 0.06 ng/kg/day (nondietary ingestion), and 0.27 ng/kg/day (inhalation); their estimated median excreted amount of urinary BPA was 114 ng/kg/day. Our multivariable regression model showed that dietary intake of BPA (p = 0.04) and creatinine concentration (p = 0.004) were significant predictors of urinary BPA excretion, collectively explaining 17% of the variability in excretion. Dietary ingestion of BPA accounted for >95% of the children's excreted amounts of urinary BPA. |
Transmission dynamics of Francisella tularensis subspecies and clades by nymphal Dermacentor variabilis (Acari: Ixodidae)
Reese SM , Dietrich G , Dolan MC , Sheldon SW , Piesman J , Petersen JM , Eisen RJ . Am J Trop Med Hyg 2010 83 (3) 645-52 In the United States, the American dog tick, Dermacentor variabilis (Say) is considered an important biological vector of Francisella tularensis, the etiologic agent of tularemia. In this study, we evaluated the vector efficiency of nymphal D. variabilis infected as larvae with differing clades and subspecies (A1b, A2, and type B) of F. tularensis. In all cases, D. variabilis larvae were able to acquire, maintain, and transstadially transmit F. tularensis. Significant replication of the bacteria also occurred in infected nymphs. Transmission of F. tularensis to Swiss Webster mice was not observed with A1b, and low rates were observed with A2 (8.0%) and type B (13.5%). Negative effects on tick survivorship were also observed for A1b, A2, and type B infections. Our results provide evidence of a high fitness cost and low transmission rates during the immature stages, suggesting that D. variabilis may play a limited role in enzootic maintenance of F. tularensis. |
Virulence differences among Francisella tularensis subsp. tularensis clades in mice
Molins CR , Delorey MJ , Yockey BM , Young JW , Sheldon SW , Reese SM , Schriefer ME , Petersen JM . PLoS One 2010 5 (4) e10205 Francisella tularensis subspecies tularensis (type A) and holarctica (type B) are of clinical importance in causing tularemia. Molecular typing methods have further separated type A strains into three genetically distinct clades, A1a, A1b and A2. Epidemiological analyses of human infections in the United States suggest that A1b infections are associated with a significantly higher mortality rate as compared to infections caused by A1a, A2 and type B. To determine if genetic differences as defined by molecular typing directly correlate with differences in virulence, A1a, A1b, A2 and type B strains were compared in C57BL/6 mice. Here we demonstrate significant differences between survival curves for infections caused by A1b versus A1a, A2 and type B, with A1b infected mice dying earlier than mice infected with A1a, A2 or type B; these results were conserved among multiple strains. Differences were also detected among type A clades as well as between type A clades and type B with respect to bacterial burdens, and gross anatomy in infected mice. Our results indicate that clades defined within F. tularensis subsp. tularensis by molecular typing methods correlate with virulence differences, with A1b strains more virulent than A1a, A2 and type B strains. These findings indicate type A strains are not equivalent with respect to virulence and have important implications for public health as well as basic research programs. |
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