Last data update: Apr 29, 2024. (Total: 46658 publications since 2009)
Records 1-30 (of 174 Records) |
Query Trace: Gao R[original query] |
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School closures due to seasonal influenza: a prospective data collection-based study of eleven influenza seasons-United States, 2011-2022
Zviedrite N , Jahan F , Zheteyeva Y , Gao H , Uzicanin A . Lancet Reg Health Am 2024 34 100741 BACKGROUND: While numerous studies explore pandemic-associated school closures, literature is scant regarding seasonal influenza-associated closures. We previously reported summaries on COVID-19 pandemic-related school closures in the United States (US), which affected virtually all schools in the nation. The current prospective study aims to address the knowledge gap for seasonal influenza-related closures in the United States. METHODS: We conducted systematic daily online searches from August 1, 2011 to June 30, 2022, to identify public announcements of unplanned school closures in the US lasting ≥1 day, selecting those that mentioned influenza and influenza-like illness (ILI) as reason for school closure (ILI-SCs). We studied ILI-SC temporal patterns and compared them with reported outpatient ILI-related healthcare visits. FINDINGS: We documented that ILI-SCs occurred annually, with yearly totals ranging from 11 ILI-SCs in both the 2013-2014 and 2020-2021 school years to 2886 ILI-SCs in the 2019-2020 school year among more than 100,000 kindergarten through twelfth grade schools in the US. ILI-SCs occurred concurrently with widespread illness and the strongest correlations were observed during influenza A (H3N2)-dominant seasons, most notably in the 2016-2017 (Spearman rank correlation (r(s)) = 0.83) and the 2017-2018 (r(s) = 0.84) school years. ILI-SCs were heavily centered in U.S. Department of Health and Human Services Region 4 (states of Alabama, Florida, Georgia, Kentucky, Mississippi, North Carolina, South Carolina, and Tennessee) [60% (6040/9166, Region 4/Total school closures)] and disproportionately impacted rural and lower-income communities. INTERPRETATION: Outside of a pandemic, disease-related school closures are extreme and generally rare events for US schools and communities. Timely compilation of publicly available ILI-SC announcements could enhance influenza surveillance, particularly in severe influenza seasons or pandemics when ILI-SCs are prevalent. FUNDING: This work was supported by the U.S. Centers for Disease Control and Prevention. Co-authors (NZ, YZ, HG, AU) were or are US CDC employees, and FJ was a contractor through Cherokee Nation Operational Solutions, LLC, which supported FJ's salary, but had no additional role in the study. |
Correction: The One Health High-Level Expert Panel (OHHLEP)
Mettenleiter TC , Markotter W , Charron DF , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Morand S , Smolenskiy V , Zhou L . One Health Outlook 2024 6 (1) 6 |
Immunological response to fractional-dose yellow fever vaccine administered during an outbreak in Kinshasa, Democratic Republic of the Congo: results 5 years after vaccination from a prospective cohort study
Doshi RH , Mukadi PK , Casey RM , Kizito GM , Gao H , Nguete UB , Laven J , Sabi L , Kaba DK , Muyembe-Tamfum JJ , Hyde TB , Ahuka-Mundeke S , Staples JE . Lancet Infect Dis 2024 BACKGROUND: In 2016, outbreaks of yellow fever in Angola and the Democratic Republic of the Congo led to a global vaccine shortage. A fractional dose of 17DD yellow fever vaccine (containing one-fifth [0·1 ml] of the standard dose) was used during a pre-emptive mass campaign in August, 2016, in Kinshasa, Democratic Republic of the Congo among children aged 2 years and older and non-pregnant adults (ie, those aged 18 years and older). 1 year following vaccination, 97% of participants were seropositive; however, the long-term durability of the immune response is unknown. We aimed to conduct a prospective cohort study and invited participants enrolled in the previous evaluation to return 5 years after vaccination to assess durability of the immune response. METHODS: Participants returned to one of six health facilities in Kinshasa in 2021, where study staff collected a brief medical history and blood specimen. We assessed neutralising antibody titres against yellow fever virus using a plaque reduction neutralisation test with a 50% cutoff (PRNT(50)). Participants with a PRNT(50) titre of 10 or higher were considered seropositive. The primary outcome was the proportion of participants seropositive at 5 years. FINDINGS: Among the 764 participants enrolled, 566 (74%) completed the 5-year visit. 5 years after vaccination, 539 (95·2%, 95% CI 93·2-96·7) participants were seropositive, including 361 (94·3%, 91·5-96·2) of 383 who were seronegative and 178 (97·3%, 93·8-98·8) of 183 who were seropositive at baseline. Geometric mean titres (GMTs) differed significantly across age groups for those who were initially seronegative with the lowest GMT among those aged 2-5 years and highest among those aged 13 years and older. INTERPRETATION: A fractional dose of the 17DD yellow fever vaccine induced an immunologic response with detectable titres at 5 years among the majority of participants in the Democratic Republic of the Congo. These findings support the use of fractional-dose vaccination for outbreak prevention with the potential for sustained immunity. FUNDING: Gavi, the Vaccine Alliance through the CDC Foundation. TRANSLATION: For the French translation of the abstract see Supplementary Materials section. |
Epidemiologic and genetic characteristics of mumps viruses isolated in China from 1995 to 2010.
Cui A , Zhu Z , Chen M , Zheng H , Liu L , Wang Y , Ma Y , Wang C , Fang X , Li P , Guan R , Wang S , Zhou J , Zheng L , Gao H , Ding Z , Li L , Bo F , Sun Z , Zhang Z , Feng D , He J , Chen H , Jin L , Rota PA , Xu W . Infect Genet Evol 2014 21 384-90 The epidemiologic and genetic characteristics of mumps viruses detected in China from 1995 to 2010 were analyzed in this study. Mumps remains endemic in China with a high overall incidence rate. The incidence of mumps in Western China was higher than that in other regions of the country. Each year, most of mumps cases occurred between April and July, but a small peak also occurred in November and December. Mumps cases primarily affected the under 15 year old age group. Virologic data demonstrated that genotype F was the predominant circulating genotype throughout China for at least 15 years and no other genotype was detected between 1995 and 2010. Analysis of sequence data from the small hydrophobic (SH) gene indicated that multiple transmission chains of genotype F were found in various provinces of China, with no apparent chronologic and geographic restriction. This is the first report describing the epidemiology of mumps and genetic characterization of mumps viruses at the national level in China. |
The One Health High-Level Expert Panel (OHHLEP)
Mettenleiter TC , Markotter W , Charron DF , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Chaudhary A , Zanella JRC , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Morand S , Smolenskiy V , Zhou L . One Health Outlook 2023 5 (1) 18 One Health is an integrative and systemic approach to health, based on the understanding that human, animal and ecosystem health are inextricably linked. These interconnections and vulnerabilities were once more clearly demonstrated by the COVID-19 pandemic. This led the heads of the United Nations Food and Agriculture Organization (FAO), the United Nations Environment Programme (UNEP), the World Health Organization (WHO), and the World Organization for Animal Health (WOAH; founded as OIE), to enhance their science-based cross-sectoral collaboration by creating a multidisciplinary One Health High-Level Expert Panel (OHHLEP) to provide technical and scientific advice on One Health issues. Out of over 700 applications from all over the world, the four international partners FAO, WHO, WOAH and UNEP selected 26 experts from 24 countries as members of the OHHLEP. The multisectoral and transdisciplinary expertise present in OHHLEP members covers a wide range including animal, human and environmental health, biodiversity conservation and social sciences. The panel was conceived following a proposal by the French and German governments at the Paris Peace Forum in November 2020. It drew on the already existing FAO-OIE-WHO Tripartite intersectoral cooperation on One Health issues. In 2021, UNEP joined to form the Tripartite plus UNEP which was formally transformed into the ‘Quadripartite Collaboration for One Health’ in March 2022 and which now acts as the partner for engaging with OHHLEP. This is the first time that a global advisory panel on One Health has been created as a centre for expert advice. |
Predictors for uptake of vaccines offered during the second year of life: Second dose of measles-containing vaccine and meningococcal serogroup A-containing vaccine, Ghana, 2020
Muhoza P , Shah MP , Gao H , Amponsa-Achiano K , Quaye P , Opare W , Okae C , Aboyinga PN , Opare KL , Wardle MT , Wallace AS . Vaccines (Basel) 2023 11 (10) BACKGROUND: Understanding the drivers of coverage for vaccines offered in the second year of life (2YL) is a critical focus area for Ghana's life course approach to vaccination. This study characterizes the predictors of vaccine receipt for 2YL vaccines-meningococcal serogroup A conjugate vaccine (MACV) and the second dose of measles-containing vaccine (MCV2)-in Ghana. METHODS: 1522 children aged 18-35 months were randomly sampled through household surveys in the Greater Accra Region (GAR), Northern Region (NR), and Volta Region (VR). The association between predictors and vaccination status was modeled using logistic regression with backwards elimination procedures. Predictors included child, caregiver, and household characteristics. RESULTS: Coverage was high for infant vaccines (>85%) but lower for 2YL vaccines (ranging from 60.2% for MACV in GAR to 82.8% for MCV2 in VR). Predictors of vaccination status varied by region. Generally, older, first-born children, those living in rural settlements and those who received their recommended infant vaccines by their first birthday were the most likely to have received 2YL vaccines. Uptake was higher among those with older mothers and children whose caregivers were aware of the vaccination schedule. CONCLUSIONS: Improving infant immunization uptake through increased community awareness and targeted strategies, such as parental reminders about vaccination visits, may improve 2YL vaccination coverage. |
Moving cholera vaccines ahead of the epidemic curve
Memish ZA , Blumberg L , Al-Maani AS , Baru R , Dube E , Gao GF , Jernigan DB , Leo YS , Peiris JSM , Masud JHB , McVernon J , Nonvignon J , Ogunsola FT , Reese H , Safdar RM , Ungchusak K , Wieler LH , Heymann D . Lancet 2023 The ongoing multi-country cholera outbreaks deserve greater attention and higher prioritisation globally.1 Since the early 1800s, there have been seven characterised global outbreaks of cholera. The seventh and current pandemic has been causing considerable illness effects since the early 1960s.2 Most recently, floods, droughts, natural disasters, and conflicts have displaced millions of people who have restricted access to clean water and live in settings with poor sewage management and increasing disease risk, further increasing the devasting effect of cholera around the globe.3 Currently, 1 billion people are at risk of contracting cholera and, concerningly, 28 countries with outbreaks in 2023, and 24 countries with active outbreaks were recorded by WHO by Sept 10, 2023 alone.4 In addition, recent outbreaks have had a high case fatality rate.5 The average cholera case fatality rate reported globally in 2021 was 1·9% (2·9% in Africa), a significant increase above the accepted target rate (<1%) and the highest recorded in over a decade.1, 5 Preliminary data suggest a similar trend for 2022 and 2023.1 Cholera is an old adversary that is both preventable and treatable.5 Despite widespread calls for strengthened pandemic preparedness and response, the global public health community are failing to apply lessons learned from COVID-19 to old challenges such as cholera. A key lesson learned from the COVID-19 pandemic is that early, rapid, and aggressive action is crucial in implementing public health interventions and countermeasure development.6 |
Structural basis of the American mink ACE2 binding by Y453F trimeric spike glycoproteins of SARS-CoV-2
Ahn H , Calderon BM , Fan X , Gao Y , Horgan NL , Jiang N , Blohm DS , Hossain J , Rayyan NWK , Osman SH , Lin X , Currier M , Steel J , Wentworth DE , Zhou B , Liang B . J Med Virol 2023 95 (10) e29163 Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) enters the host cell by binding to angiotensin-converting enzyme 2 (ACE2). While evolutionarily conserved, ACE2 receptors differ across various species and differential interactions with Spike (S) glycoproteins of SARS-CoV-2 viruses impact species specificity. Reverse zoonoses led to SARS-CoV-2 outbreaks on multiple American mink (Mustela vison) farms during the pandemic and gave rise to mink-associated S substitutions known for transmissibility between mink and zoonotic transmission to humans. In this study, we used bio-layer interferometry (BLI) to discern the differences in binding affinity between multiple human and mink-derived S glycoproteins of SARS-CoV-2 and their respective ACE2 receptors. Further, we conducted a structural analysis of a mink variant S glycoprotein and American mink ACE2 (mvACE2) using cryo-electron microscopy (cryo-EM), revealing four distinct conformations. We discovered a novel intermediary conformation where the mvACE2 receptor is bound to the receptor-binding domain (RBD) of the S glycoprotein in a "down" position, approximately 34° lower than previously reported "up" RBD. Finally, we compared residue interactions in the S-ACE2 complex interface of S glycoprotein conformations with varying RBD orientations. These findings provide valuable insights into the molecular mechanisms of SARS-CoV-2 entry. |
Elucidating regulatory processes of intense physical activity by multi-omics analysis
Nakayasu ES , Gritsenko MA , Kim YM , Kyle JE , Stratton KG , Nicora CD , Munoz N , Navarro KM , Claborne D , Gao Y , Weitz KK , Paurus VL , Bloodsworth KJ , Allen KA , Bramer LM , Montes F , Clark KA , Tietje G , Teeguarden J , Burnum-Johnson KE . Mil Med Res 2023 10 (1) 48 BACKGROUND: Physiological and biochemical processes across tissues of the body are regulated in response to the high demands of intense physical activity in several occupations, such as firefighting, law enforcement, military, and sports. A better understanding of such processes can ultimately help improve human performance and prevent illnesses in the work environment. METHODS: To study regulatory processes in intense physical activity simulating real-life conditions, we performed a multi-omics analysis of three biofluids (blood plasma, urine, and saliva) collected from 11 wildland firefighters before and after a 45 min, intense exercise regimen. Omics profiles post- versus pre-exercise were compared by Student's t-test followed by pathway analysis and comparison between the different omics modalities. RESULTS: Our multi-omics analysis identified and quantified 3835 proteins, 730 lipids and 182 metabolites combining the 3 different types of samples. The blood plasma analysis revealed signatures of tissue damage and acute repair response accompanied by enhanced carbon metabolism to meet energy demands. The urine analysis showed a strong, concomitant regulation of 6 out of 8 identified proteins from the renin-angiotensin system supporting increased excretion of catabolites, reabsorption of nutrients and maintenance of fluid balance. In saliva, we observed a decrease in 3 pro-inflammatory cytokines and an increase in 8 antimicrobial peptides. A systematic literature review identified 6 papers that support an altered susceptibility to respiratory infection. CONCLUSION: This study shows simultaneous regulatory signatures in biofluids indicative of homeostatic maintenance during intense physical activity with possible effects on increased infection susceptibility, suggesting that caution against respiratory diseases could benefit workers on highly physical demanding jobs. |
Developing One Health surveillance systems
Hayman DTS , Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Becerra NC , Charron DF , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Khaitsa M , Machalaba C , Mackenzie JS , Markotter W , Mettenleiter TC , Morand S , Smolenskiy V , Zhou L , Koopmans M . One Health 2023 17 100617 The health of humans, domestic and wild animals, plants, and the environment are inter-dependent. Global anthropogenic change is a key driver of disease emergence and spread and leads to biodiversity loss and ecosystem function degradation, which are themselves drivers of disease emergence. Pathogen spill-over events and subsequent disease outbreaks, including pandemics, in humans, animals and plants may arise when factors driving disease emergence and spread converge. One Health is an integrated approach that aims to sustainably balance and optimize human, animal and ecosystem health. Conventional disease surveillance has been siloed by sectors, with separate systems addressing the health of humans, domestic animals, cultivated plants, wildlife and the environment. One Health surveillance should include integrated surveillance for known and unknown pathogens, but combined with this more traditional disease-based surveillance, it also must include surveillance of drivers of disease emergence to improve prevention and mitigation of spill-over events. Here, we outline such an approach, including the characteristics and components required to overcome barriers and to optimize an integrated One Health surveillance system. © 2023 The Authors |
New insights into the neuraminidase-mediated hemagglutination activity of influenza A(H3N2) viruses
Gao R , Pascua PNQ , Nguyen HT , Chesnokov A , Champion C , Mishin VP , Wentworth DE , Gubareva LV . Antiviral Res 2023 218 105719 Influenza virus neuraminidase (NA) can act as a receptor-binding protein, a role commonly attributed to hemagglutinin (HA). In influenza A(H3N2) viruses, three NA amino acid residues have previously been associated with NA-mediated hemagglutination: T148, D151, and more recently, H150. These residues are part of the 150-loop of the NA monomer. Substitutions at 148 and 151 arise from virus propagation in laboratory cell cultures, whereas changes at 150 occurred during virus evolution in the human host. In this study, we examined the effect of natural amino acid polymorphism at position 150 on NA-mediated hemagglutination. Using the A/Puerto Rico/8/34 backbone, we generated a comprehensive panel of recombinant A(H3N2) viruses that have different NAs but shared an HA that displays poor binding to red blood cells (RBCs). None of the tested substitutions at 150 (C, H, L, R, and S) promoted NA-binding. However, we identified two new determinants of NA-binding, Q136K and T439R, that emerged during virus culturing. Similar to T148I, both Q136K and T439R reduced NA enzyme activity by 48-86% and inhibition (14- to 173-fold) by the NA inhibitor zanamivir. NA-binding was observed when a virus preparation contained approximately 10% of NA variants with either T148I or T439R, highlighting the benefit of using deep sequencing in virus characterization. Taken together, our findings provide new insights into the molecular mechanisms underlying the ability of NA to function as a binding protein. Information gained may aid in the design of new and improved NA-targeting antivirals. |
Ebola vaccine uptake and attitudes among healthcare workers in North Kivu, Democratic Republic of the Congo, 2021
Doshi RH , Garbern SC , Kulkarni S , Perera SM , Fleming MK , Muhayangabo RF , Ombeni AB , Tchoualeu DD , Kallay R , Song E , Powell J , Gainey M , Glenn B , Mutumwa RM , Hans Bateyi Mustafa S , Earle-Richardson G , Gao H , Abad N , Soke GN , Fitter DL , Hyde TB , Prybylski D , Levine AC , Jalloh MF , Mbong EN . Front Public Health 2023 11 1080700 INTRODUCTION: During the 2018-2020 Ebola virus disease (EVD) outbreak in the eastern part of the Democratic Republic of the Congo (DRC), prevention and control measures, such as Ebola vaccination were challenging by community mistrust. We aimed to understand perceptions regarding Ebola vaccination and identify determinants of Ebola vaccine uptake among HCWs. METHODS: In March 2021, we conducted a cross-sectional survey among 438 HCWs from 100 randomly selected health facilities in three health zones (Butembo, Beni, Mabalako) affected by the 10th EVD outbreak in North Kivu, DRC. HCWs were eligible if they were ≥ 18 years and were working in a health facility during the outbreak. We used survey logistic regression to assess correlates of first-offer uptake (i.e., having received the vaccine the first time it was offered vs. after subsequent offers). RESULTS: Of the 438 HCWs enrolled in the study, 420 (95.8%) reported that they were eligible and offered an Ebola vaccine. Among those offered vaccination, self-reported uptake of the Ebola vaccine was 99.0% (95% confidence interval (CI) [98.5-99.4]), but first-offer uptake was 70.2% (95% CI [67.1, 73.5]). Nearly all HCWs (94.3%; 95% CI [92.7-95.5]) perceived themselves to be at risk of contracting EVD. The most common concern was that the vaccine would cause side effects (65.7%; 95% CI [61.4-69.7]). In the multivariable analysis, mistrust of the vaccine source or how the vaccine was produced decreased the odds of first-time uptake. DISCUSSION: Overall uptake of the Ebola vaccine was high among HCWs, but uptake at the first offer was substantially lower, which was associated with mistrust of the vaccine source. Future Ebola vaccination efforts should plan to make repeated vaccination offers to HCWs and address their underlying mistrust in the vaccines, which can, in turn, improve community uptake. |
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 |
COVID-19-associated school closures and related efforts to sustain education and subsidized meal programs, United States, February 18–June 30, 2020 (preprint)
Zviedrite N , Hodis JD , Jahan F , Gao H , Uzicanin A . medRxiv 2021 2021.03.05.21252848 Pre-emptive school closures are frontline community mitigation measures recommended by CDC for implementation during severe pandemics. This study describes the spatiotemporal patterns of publicly announced school closures implemented in response to the coronavirus disease 2019 (COVID-19) pandemic and assesses how public K-12 districts adjusted their methods of education delivery and provision of subsidized meals. During February 18–June 30, 2020, we used daily systematic media searches to identify publicly announced coronavirus disease 2019 (COVID-19)–related school closures lasting ≥1 day in the United States (US). We also collected statewide school closure policies from state government websites. Data on distance learning and subsidized meal programs were collected from a stratified sample of 600 school districts. The first COVID-19–associated school closure occurred on February 27, 2020 in Washington state. By March 30, 2020, all but one US public school districts were closed, representing the first-ever nearly synchronous nationwide closure of public K-12 schools in the US. Approximately 100,000 public schools were closed for ≥8 weeks because of COVID-19, affecting >50 million K-12 students. Of 600 districts sampled, the vast majority offered distance learning (91.0%) and continued provision of subsidized meal programs (78.8%) during the closures. Despite the sudden and prolonged nature of COVID-19–associated school closures, schools demonstrated flexibility by implementing distance learning and alternate methods to continue subsidized meal programs.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis study was supported by the United States Centers for Disease Control and Prevention (http://www.cdc.gov/). Several co-authors are or were employees (NZ HG AU) or contractors (FJ) of the US CDC at the time of the study. During the study period, JH was a fellow appointed through the Research Participation Program at the US CDC administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US CDC.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:The project underwent ethical review at the Centers for Disease Control and Prevention and was determined not to involve human subjects; it was therefore not subject to institutional review board review requirements.All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesThe authors confirm that all data underlying the findings are fully available without restriction. Data are available from Google (www.google.com), Google News (news.google.com), and the National Center for Education Statistics (nces.ed.gov). The search and linking strategy used for these data sources is detailed within the paper. |
Influenza and other respiratory viral infections associated with absence from school among schoolchildren in Pittsburgh, Pennsylvania, USA: a cohort study (preprint)
Read JM , Zimmer S , Vukotich CJr , Schweizer ML , Galloway D , Lingle C , Yearwood G , Calderone P , Noble E , Quadelacy T , Grantz K , Rinaldo C , Gao H , Rainey J , Uzicanin A , Cummings DAT . medRxiv 2020 2020.04.16.20068593 Background Information on the etiology and age-specific burden of respiratory viral infections among school-aged children remains limited.Methods We conducted a cohort study to determine the etiology of ILI (influenza like illness) among 2,519 K–12 students during the 2012–13 influenza season. We obtained nasal swabs from students with ILI-related absences. Generalized linear mixed-effect regressions determined associations of outcomes, including ILI and laboratory-confirmed respiratory virus infection, with school grade and other covariates.Results Overall, 459 swabs were obtained from 552 ILI–related absences. Respiratory viruses were found in 292 (63.6%) samples. Influenza was found in 189 (41.2%) samples. with influenza B found in 134 (70.9%). Rates of influenza B were significantly higher in grades 1 (10.1%, 95% CI 6.8%–14.4%), 2 (9.7%, 6.6%–13.6%), 3 (9.3%, 6.3%–13.2%), and 4 (9.9%, 6.8%–13.8%) than in kindergarteners (3.2%, 1.5%–6.0%). After accounting for grade, sex and self-reported vaccination status, influenza B infection risk was lower among kindergarteners in half-day programs compared to kindergarteners in full-day programs (OR = 0.19; 95% CI 0.08–0.45).Conclusions ILI and influenza infection is concentrated in younger schoolchildren. Reduced infection by respiratory viruses is associated with a truncated school day for kindergarteners, but requires further investigation in other grades and populations.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by Cooperative Agreement number [1U01CK00179] from the US Centers for Disease Control and Prevention (CDC, www.cdc.gov). The findings and conclusions in this study are solely the responsibility of the authors and do not necessarily represent the official position of CDC. JMR acknowledges additional support from the Engineering and Physical Sciences Research Council (EP/N014499/1).Author DeclarationsAll relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript.YesAll necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived.YesI understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).YesI have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.YesData for reproduction of major results and figures is made available through the DRYAD archive. |
Age-specific social mixing of school-aged children in a US setting using proximity detecting sensors and contact surveys (preprint)
Grantz KH , Cummings DAT , Zimmer S , Vukotich C , Galloway D , Schweizer ML , Guclu H , Cousins J , Lingle C , Yearwood GMH , Li K , Calderone PA , Noble E , Gao H , Rainey J , Uzicanin A , Read JM . medRxiv 2020 Comparisons of the utility and accuracy of methods for measuring social interactions relevant to disease transmission are rare. To increase the evidence base supporting specific methods to measure social interaction, we compared data from self-reported contact surveys and wearable proximity sensors from a cohort of schoolchildren in the Pittsburgh metropolitan area. Although the number and type of contacts recorded by each participant differed between the two methods, we found good correspondence between the two methods in aggregate measures of age-specific interactions. Fewer, but longer, contacts were reported in surveys, relative to the generally short proximal interactions captured by wearable sensors. When adjusted for expectations of proportionate mixing, though, the two methods produced highly similar, assortative age-mixing matrices. These aggregate mixing matrices, when used in simulation, resulted in similar estimates of risk of infection by age. While proximity sensors and survey methods may not be interchangeable for capturing individual contacts, they can generate highly correlated data on age-specific mixing patterns relevant to the dynamics of respiratory virus transmission. |
Adapterama II: Universal amplicon sequencing on Illumina platforms (TaggiMatrix) (preprint)
Glenn TC , Pierson TW , Bayona-Vásquez NJ , Kieran TJ , Hoffberg SL , Thomas IV JC , Lefever DE , Finger JW , Gao B , Bian X , Louha S , Kolli RT , Bentley KE , Rushmore J , Wong K , Shaw TI , Rothrock MJ Jr , McKee AM , Guo TL , Mauricio R , Molina M , Cummings BS , Lash LH , Lu K , Gilbert GS , Hubbell SP , Faircloth BC . bioRxiv 2019 619544 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. Most NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5’ end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (eight forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy. |
Evaluation of correlates of protection against influenza A(H3N2) and A(H1N1)pdm09 infection: Applications to the hospitalized patient population (preprint)
Petrie JG , Martin ET , Truscon R , Johnson E , Cheng CK , McSpadden EJ , Malosh RE , Lauring AS , Lamerato LE , Eichelberger MC , Ferdinands JM , Monto AS . bioRxiv 2018 416628 Background Influenza vaccines are important for prevention of influenza-associated hospitalization. Assessments of serologic correlates of protection can support interpretation of influenza vaccine effectiveness evaluations in hospitalized populations.Methods Serum specimens collected at admission from adults hospitalized for treatment of acute respiratory illnesses during two influenza seasons were tested in hemagglutination-inhibition (HAI) and neuraminidase-inhibition (NAI) assays. We evaluated the suitability of these specimens as proxies for pre-infection immune status, and measured associations between antibody titers and influenza vaccination and infectionResults Specimens were collected within 3 days of illness onset from 65% of participants; geometric mean titers (GMTs) did not vary by day of collection. In both seasons, vaccinated participants had higher HAI and NAI GMTs than unvaccinated participants. HAI titers against the 2014-2015 A(H3N2) vaccine strain did not correlate with protection from infection with antigenically-drifted A(H3N2) viruses that circulated that season. In contrast, higher HAI titers against the A(H1N1)pdm09 vaccine strain were associated with reduced odds of A(H1N1)pdm09 infection in 2015-2016.Conclusions Serum collected after hospital admission can be used to assess correlates of protection against influenza infection. Broader implementation of similar studies would provide an opportunity to understand the successes and shortcomings of current influenza vaccines.We thank Jin Gao and Laura Couzens for technical support and are indebted to St Jude Children’s Research Hospital for plasmids that were used to generate reassortant influenza viruses. |
Antibodies against egg- and cell-grown influenza A(H3N2) viruses in adults hospitalized during the 2017-2018 season (preprint)
Levine MZ , Martin ET , Petrie JG , Lauring AS , Holiday C , Jefferson S , Fitzsimmons WJ , Johnson E , Ferdinands JM , Monto AS . bioRxiv 2018 439471 Background The 2017-2018 US influenza season was severe with low vaccine effectiveness. Circulating A(H3N2) viruses from multiple genetic groups were antigenically similar to cell-grown vaccine strains. However, most influenza vaccines are egg-propagated.Methods Serum was collected shortly after illness onset from 15 PCR confirmed A(H3N2) infected cases and 15 uninfected (controls) hospitalized adults enrolled in an influenza vaccine effectiveness study.Geometric mean titers against egg- and cell-grown A/Hong Kong/4801/2014 A(H3N2) vaccine strains and representative circulating viruses (including A/Washington/16/2017) were determined by microneutralization (MN) assays. Independent effects of strain-specific titers on susceptibility were estimated by logistic regression.Results MN titers against egg-A/Hong Kong were significantly higher among those who were vaccinated (MN GMT: 173 vs 41; P = 0.01). However, antibody titers to cell-grown viruses were much lower in all individuals (P>0.05) regardless of vaccination. In unadjusted models, a 2-fold increase in MN titers against egg-A/Hong Kong was not significantly protective against infection (29% reduction; p=0.09), but a similar increase in cell-A/Washington titer (3C.2a2) was protective (60% reduction; p=0.02). A similar increase in egg-A/Hong Kong titer was not significantly associated with odds of infection when adjusting for MN titers against A/Washington (15% reduction; P=0.61). A 54% reduction of odds of infection was observed with a 2-fold increase in A/Washington (not significant; P=0.07), adjusted for egg-A/Hong Kong titer.Conclusion Although individuals vaccinated in 2017-2018 had high antibody titers against the egg-adapted vaccine strain, antibody responses to cell-grown circulating viruses may not be sufficient to provide protection, likely due to egg-adaptation in the vaccine.We thank Maryna Eichelberger, Hongquan Wan, Jin Gao, and Laura Couzens (Food and Drug Administration) for technical support and providing reassortant influenza viruses for use in the enzyme-linked lectin assays. St Jude Children’s Research Hospital provided plasmids that were used to generate these reassortant influenza viruses. We thank Mrs F Liaini Gross, Lauren Horner and Makeda Kay from Influenza Division, Centers for Disease Control and Prevention for technical support for virus propagation and specimen management. |
The contribution of parent-to-offspring transmission of telomeres to the heritability of telomere length in humans (preprint)
Delgado DA , Zhang C , Demanelis K , Chen LS , Gao J , Roy S , Shinkle J , Sabarinathan M , Argos M , Tong L , Ahmed A , Islam T , Rakibuz-Zaman M , Sarwar G , Shahriar H , Rahman M , Yunus M , Doherty JA , Jasmine F , Kibriya MG , Ahsan H , Pierce BL . bioRxiv 2018 276030 Leukocyte telomere length (LTL) is a heritable trait with two potential sources of heritability (h2): inherited variation in non-telomeric regions (e.g., SNPs that influence telomere maintenance) and variability in the lengths of telomeres in gametes that produce offspring zygotes (i.e., “direct” inheritance). Prior studies of LTL h2 have not attempted to disentangle these two sources. Here, we use a novel approach for detecting the direct inheritance of telomeres by studying the association between identity-by-descent (IBD) sharing at chromosome ends and phenotypic similarity in LTL. We measured genome-wide SNPs and LTL for a sample of 5,069 Bangladeshi adults with substantial relatedness. For each of the 7,254 relative pairs identified, we used SNPs near the telomeres to estimate the number of chromosome ends shared IBD, a proxy for the number of telomeres shared IBD (Tshared). We then estimated the association between Tshared and the squared pairwise difference in LTL ((ΔLTL)2) within various classes of relatives (siblings, avuncular, cousins, and distant), adjusting for overall genetic relatedness (ϕ). The association between Tshared and (ΔLTL)2 was inverse among all relative pair types. In a meta-analysis including all relative pairs (ϕ >0.05), the association between Tshared and (ΔLTL)2 (P=0.002) was stronger than the association between ϕ and (ΔLTL)2 (P=0.45). Our results provide strong evidence that telomere length (TL) in parental germ cells impacts TL in offspring cells and contributes to LTL h2 despite telomere “reprogramming” during embryonic development. Applying our method to larger studies will enable robust estimation of LTL h2 attributable to direction transmission. |
Causes, characteristics, and patterns of prolonged unplanned school closures prior to the COVID-19 pandemic - United States, 2011 - 2019 (preprint)
Jahan FA , Zviedrite N , Gao H , Ahmed F , Uzicanin A . medRxiv 2021 08 Introduction Outside of pandemics, there is little information about occurrence of prolonged unplanned K-12 school closures (PUSC). We describe here the reasons, characteristics, and patterns of PUSC in the United States during 8 consecutive inter-pandemic academic years, 2011-2019. Methods From August 1, 2011 through June 30, 2019, daily systematic online searches were conducted to collect data on publicly announced unplanned school closures lasting >=1 school days in the United States. Closures were categorized as prolonged when schools were closed for >=5 unplanned days (approximating one full workweek), excluding weekends and scheduled days off per school calendars. Results During the eight academic years, a total of 22,112 PUSCs were identified, affecting over 800,000 teachers and 13 million students that resulted in 91.5 million student-days lost. A median of 62.9% of students in PUSC-affected schools were eligible for subsidized school meals. Most affected schools were in cities (35%) and suburban areas (33%). Natural disasters (47%), adverse weather conditions (35%), and budget/teacher strikes (15%) were the most frequently cited reasons for PUSC; illness accounted for 1%, and building/facility issues, environmental issues and violence together accounted for the remaining 2%. The highest number of PUSCs occurred in Health and Human Services Regions 2, 3, 4, and 6 encompassing areas that are frequently in the path of hurricanes and tropical storms. The majority of PUSCs in these regions were attributed to a handful of hurricanes during the fall season, including hurricanes Sandy, Irma, Harvey, Florence, and Matthew. Conclusions PUSCs occur annually in the United States due to a variety of causes and are associated with a substantive loss of student-days for in-school learning. Both these prior experiences with PUSCs and those during the current COVID-19 pandemic illustrate a need for creating sustainable solutions for high-quality distance learning and innovative supplemental feeding programs nationwide, especially in disaster-prone areas. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
Self-Reported Mask Use among Persons with or without SARS CoV-2 Vaccination -United States, December 2020-August 2021 (preprint)
Calamari LE , Weintraub WS , Santos R , Gibbs M , Bertoni AG , Ward LM , Saydah S , Plumb ID , Runyon MS , Wierzba TF , Sanders JW , Herrington D , Espeland MA , Williamson J , Mongraw-Chaffin M , Bertoni A , Alexander-Miller MA , Castri P , Mathews A , Munawar I , Seals AL , Ostasiewski B , Ballard CAP , Gurcan M , Ivanov A , Zapata GM , Westcott M , Blinson K , Blinson L , Mistysyn M , Davis D , Doomy L , Henderson P , Jessup A , Lane K , Levine B , McCanless J , McDaniel S , Melius K , O'Neill C , Pack A , Rathee R , Rushing S , Sheets J , Soots S , Wall M , Wheeler S , White J , Wilkerson L , Wilson R , Wilson K , Burcombe D , Saylor G , Lunn M , Ordonez K , O'Steen A , Wagner L , McCurdy LH , Gibbs MA , Taylor YJ , Calamari L , Tapp H , Ahmed A , Brennan M , Munn L , Dantuluri KL , Hetherington T , Lu LC , Dunn C , Hogg M , Price A , Leonidas M , Manning M , Rossman W , Gohs FX , Harris A , Priem JS , Tochiki P , Wellinsky N , Silva C , Ludden T , Hernandez J , Spencer K , McAlister L , Weintraub W , Miller K , Washington C , Moses A , Dolman S , Zelaya-Portillo J , Erkus J , Blumenthal J , Romero Barrientos RE , Bennett S , Shah S , Mathur S , Boxley C , Kolm P , Franklin E , Ahmed N , Larsen M , Oberhelman R , Keating J , Kissinger P , Schieffelin J , Yukich J , Beron A , Teigen J , Kotloff K , Chen WH , Friedman-Klabanoff D , Berry AA , Powell H , Roane L , Datar R , Correa A , Navalkele B , Min YI , Castillo A , Ward L , Santos RP , Anugu P , Gao Y , Green J , Sandlin R , Moore D , Drake L , Horton D , Johnson KL , Stover M , Lagarde WH , Daniel L , Maguire PD , Hanlon CL , McFayden L , Rigo I , Hines K , Smith L , Harris M , Lissor B , Cook V , Eversole M , Herrin T , Murphy D , Kinney L , Diehl P , Abromitis N , Pierre TSt , Heckman B , Evans D , March J , Whitlock B , Moore W , Arthur S , Conway J , Gallaher TR , Johanson M , Brown S , Dixon T , Reavis M , Henderson S , Zimmer M , Oliver D , Jackson K , Menon M , Bishop B , Roeth R , King-Thiele R , Hamrick TS , Ihmeidan A , Hinkelman A , Okafor C , Bray Brown RB , Brewster A , Bouyi D , Lamont K , Yoshinaga K , Vinod P , Peela AS , Denbel G , Lo J , Mayet-Khan M , Mittal A , Motwani R , Raafat M , Schultz E , Joseph A , Parkeh A , Patel D , Afridi B , Uschner D , Edelstein SL , Santacatterina M , Strylewicz G , Burke B , Gunaratne M , Turney M , Zhou SQ , Tjaden AH , Fette L , Buahin A , Bott M , Graziani S , Soni A , Mores C , Porzucek A , Laborde R , Acharya P , Guill L , Lamphier D , Schaefer A , Satterwhite WM , McKeague A , Ward J , Naranjo DP , Darko N , Castellon K , Brink R , Shehzad H , Kuprianov D , McGlasson D , Hayes D , Edwards S , Daphnis S , Todd B , Goodwin A , Berkelman R , Hanson K , Zeger S , Hopkins J , Reilly C , Edwards K , Gayle H , Redd S . medRxiv 2022 10 Wearing a facemask can help to decrease the transmission of COVID-19. We investigated self-reported mask use among subjects aged 18 years and older participating in the COVID-19 Community Research Partnership (CRP), a prospective longitudinal COVID-19 surveillance study in the mid-Atlantic and southeastern United States. We included those participants who completed >=5 daily surveys each month from December 1, 2020 through August 31, 2021. Mask use was defined as self-reported use of a face mask or face covering on every interaction with others outside the household within a distance of less than 6 feet. Participants were considered vaccinated if they reported receiving >=1 COVID-19 vaccine dose. Participants (n=17,522) were 91% non-Hispanic White, 68% female, median age 57 years, 26% healthcare workers, with 95% self-reported receiving >=1 COVID-19 vaccine dose through August; mean daily survey response was 85%. Mask use was higher among vaccinated than unvaccinated participants across the study period, regardless of the month of the first dose. Mask use remained relatively stable from December 2020 through April (range 71-80% unvaccinated; 86-93% vaccinated) and declined in both groups beginning in mid-May 2021 to 34% and 42% respectively in June 2021; mask use has increased again since July 2021. Mask use by all was lower during weekends and on Christmas and Easter, regardless of vaccination status. Independent predictors of higher mask use were vaccination, age >=65 years, female sex, racial or ethnic minority group, and healthcare worker occupation, whereas a history of self-reported prior COVID-19 illness was associated with lower use. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. This article is a US Government work. It is not subject to copyright under 17 USC 105 and is also made available for use under a CC0 license. |
COVID-19 vaccine perceptions among ebola-affected communities in North Kivu, Democratic Republic of the Congo, 2021
Garbern SC , Perera SM , Mbong EN , Kulkarni S , Fleming MK , Ombeni AB , Muhayangabo RF , Tchoualeu DD , Kallay R , Song E , Powell J , Gainey M , Glenn B , Gao H , Mutumwa RM , Mustafa SHB , Abad N , Soke GN , Prybylski D , Doshi RH , Fukunaga R , Levine AC . Vaccines (Basel) 2023 11 (5) Populations affected by humanitarian crises and emerging infectious disease outbreaks may have unique concerns and experiences that influence their perceptions toward vaccines. In March 2021, we conducted a survey to examine the perceptions toward COVID-19 vaccines and identify the factors associated with vaccine intention among 631 community members (CMs) and 438 healthcare workers (HCWs) affected by the 2018-2020 Ebola Virus Disease outbreak in North Kivu, Democratic Republic of the Congo. A multivariable logistic regression was used to identify correlates of vaccine intention. Most HCWs (81.7%) and 53.6% of CMs felt at risk of contracting COVID-19; however, vaccine intention was low (27.6% CMs; 39.7% HCWs). In both groups, the perceived risk of contracting COVID-19, general vaccine confidence, and male sex were associated with the intention to get vaccinated, with security concerns preventing vaccine access being negatively associated. Among CMs, getting the Ebola vaccine was associated with the intention to get vaccinated (RR 1.43, 95% CI 1.05-1.94). Among HCWs, concerns about new vaccines' safety and side effects (OR 0.72, 95% CI 0.57-0.91), religion's influence on health decisions (OR 0.45, 95% CI 0.34-0.61), security concerns (OR 0.52, 95% CI 0.37-0.74), and governmental distrust (OR 0.50, 95% CI 0.35-0.70) were negatively associated with vaccine perceptions. Enhanced community engagement and communication that address this population's concerns could help improve vaccine perceptions and vaccination decisions. These findings could facilitate the success of vaccine campaigns in North Kivu and similar settings. |
Prediagnostic blood levels of organochlorines and risk of non-Hodgkin lymphoma in three prospective cohorts in China and Singapore
Bassig BA , Shu XO , Sjödin A , Koh WP , Gao YT , Adams-Haduch J , Davis M , Wang R , Xiang YB , Engel LS , Purdue MP , Ji BT , Yang G , Jones RS , Langseth H , Hosgood HD , Grimsrud TK , Seow WJ , Wong JYY , Hu W , Chen D , Zheng W , Yuan JM , Lan Q , Rothman N . Int J Cancer 2020 146 (3) 839-849 Specific organochlorines (OCs) have been associated with non-Hodgkin lymphoma (NHL) with varying degrees of evidence. These associations have not been evaluated in Asia, where the high exposure and historical environmental contamination of certain OC pesticides (e.g., dichlorodiphenyltrichloroethane [DDT], hexachlorocyclohexane [HCH]) are different from Western populations. We evaluated NHL risk and prediagnostic blood levels of OC pesticides/metabolites and polychlorinated biphenyl congeners in a case-control study of 167 NHL cases and 167 controls nested within three prospective cohorts in Shanghai and Singapore. Conditional logistic regression was used to analyze lipid-adjusted OC levels and NHL risk. Median levels of p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), the primary DDT metabolite, and β-HCH were up to 12 and 65 times higher, respectively, in samples from the Asian cohorts compared to several cohorts in the United States and Norway. An increased risk of NHL was observed among those with higher β-HCH levels both overall (3rd vs. 1st tertile OR = 1.8, 95%CI = 1.0-3.2; p(trend) = 0.049) and after excluding cases diagnosed within 2 years of blood collection (3rd vs. 1st tertile OR = 2.0, 95%CI = 1.1-3.9; p(trend) = 0.03), and the association was highly consistent across the three cohorts. No significant associations were observed for other OCs, including p,p'-DDE. Our findings provide support for an association between β-HCH blood levels and NHL risk. This is a concern because substantial quantities of persistent, toxic residues of HCH are present in the environment worldwide. Although there is some evidence that DDT is associated with NHL, our findings for p,p'-DDE do not support an association. |
Prediction of Susceptibility to First-Line Tuberculosis Drugs by DNA Sequencing.
Allix-Béguec C , Arandjelovic I , Bi L , Beckert P , Bonnet M , Bradley P , Cabibbe AM , Cancino-Muñoz I , Caulfield MJ , Chaiprasert A , Cirillo DM , Clifton DA , Comas I , Crook DW , De Filippo MR , de Neeling H , Diel R , Drobniewski FA , Faksri K , Farhat MR , Fleming J , Fowler P , Fowler TA , Gao Q , Gardy J , Gascoyne-Binzi D , Gibertoni-Cruz AL , Gil-Brusola A , Golubchik T , Gonzalo X , Grandjean L , He G , Guthrie JL , Hoosdally S , Hunt M , Iqbal Z , Ismail N , Johnston J , Khanzada FM , Khor CC , Kohl TA , Kong C , Lipworth S , Liu Q , Maphalala G , Martinez E , Mathys V , Merker M , Miotto P , Mistry N , Moore DAJ , Murray M , Niemann S , Omar SV , Ong RT , Peto TEA , Posey JE , Prammananan T , Pym A , Rodrigues C , Rodrigues M , Rodwell T , Rossolini GM , Sánchez Padilla E , Schito M , Shen X , Shendure J , Sintchenko V , Sloutsky A , Smith EG , Snyder M , Soetaert K , Starks AM , Supply P , Suriyapol P , Tahseen S , Tang P , Teo YY , Thuong TNT , Thwaites G , Tortoli E , van Soolingen D , Walker AS , Walker TM , Wilcox M , Wilson DJ , Wyllie D , Yang Y , Zhang H , Zhao Y , Zhu B . N Engl J Med 2018 379 (15) 1403-1415 BACKGROUND: The World Health Organization recommends drug-susceptibility testing of Mycobacterium tuberculosis complex for all patients with tuberculosis to guide treatment decisions and improve outcomes. Whether DNA sequencing can be used to accurately predict profiles of susceptibility to first-line antituberculosis drugs has not been clear. METHODS: We obtained whole-genome sequences and associated phenotypes of resistance or susceptibility to the first-line antituberculosis drugs isoniazid, rifampin, ethambutol, and pyrazinamide for isolates from 16 countries across six continents. For each isolate, mutations associated with drug resistance and drug susceptibility were identified across nine genes, and individual phenotypes were predicted unless mutations of unknown association were also present. To identify how whole-genome sequencing might direct first-line drug therapy, complete susceptibility profiles were predicted. These profiles were predicted to be susceptible to all four drugs (i.e., pansusceptible) if they were predicted to be susceptible to isoniazid and to the other drugs or if they contained mutations of unknown association in genes that affect susceptibility to the other drugs. We simulated the way in which the negative predictive value changed with the prevalence of drug resistance. RESULTS: A total of 10,209 isolates were analyzed. The largest proportion of phenotypes was predicted for rifampin (9660 [95.4%] of 10,130) and the smallest was predicted for ethambutol (8794 [89.8%] of 9794). Resistance to isoniazid, rifampin, ethambutol, and pyrazinamide was correctly predicted with 97.1%, 97.5%, 94.6%, and 91.3% sensitivity, respectively, and susceptibility to these drugs was correctly predicted with 99.0%, 98.8%, 93.6%, and 96.8% specificity. Of the 7516 isolates with complete phenotypic drug-susceptibility profiles, 5865 (78.0%) had complete genotypic predictions, among which 5250 profiles (89.5%) were correctly predicted. Among the 4037 phenotypic profiles that were predicted to be pansusceptible, 3952 (97.9%) were correctly predicted. CONCLUSIONS: Genotypic predictions of the susceptibility of M. tuberculosis to first-line drugs were found to be correlated with phenotypic susceptibility to these drugs. (Funded by the Bill and Melinda Gates Foundation and others.). |
Adapterama II: universal amplicon sequencing on Illumina platforms (TaggiMatrix).
Glenn TC , Pierson TW , Bayona-Vásquez NJ , Kieran TJ , Hoffberg SL , Thomas Iv JC , Lefever DE , Finger JW , Gao B , Bian X , Louha S , Kolli RT , Bentley KE , Rushmore J , Wong K , Shaw TI , Rothrock MJ Jr , McKee AM , Guo TL , Mauricio R , Molina M , Cummings BS , Lash LH , Lu K , Gilbert GS , Hubbell SP , Faircloth BC . PeerJ 2019 7 e7786 Next-generation sequencing (NGS) of amplicons is used in a wide variety of contexts. In many cases, NGS amplicon sequencing remains overly expensive and inflexible, with library preparation strategies relying upon the fusion of locus-specific primers to full-length adapter sequences with a single identifying sequence or ligating adapters onto PCR products. In Adapterama I, we presented universal stubs and primers to produce thousands of unique index combinations and a modifiable system for incorporating them into Illumina libraries. Here, we describe multiple ways to use the Adapterama system and other approaches for amplicon sequencing on Illumina instruments. In the variant we use most frequently for large-scale projects, we fuse partial adapter sequences (TruSeq or Nextera) onto the 5' end of locus-specific PCR primers with variable-length tag sequences between the adapter and locus-specific sequences. These fusion primers can be used combinatorially to amplify samples within a 96-well plate (8 forward primers + 12 reverse primers yield 8 × 12 = 96 combinations), and the resulting amplicons can be pooled. The initial PCR products then serve as template for a second round of PCR with dual-indexed iTru or iNext primers (also used combinatorially) to make full-length libraries. The resulting quadruple-indexed amplicons have diversity at most base positions and can be pooled with any standard Illumina library for sequencing. The number of sequencing reads from the amplicon pools can be adjusted, facilitating deep sequencing when required or reducing sequencing costs per sample to an economically trivial amount when deep coverage is not needed. We demonstrate the utility and versatility of our approaches with results from six projects using different implementations of our protocols. Thus, we show that these methods facilitate amplicon library construction for Illumina instruments at reduced cost with increased flexibility. A simple web page to design fusion primers compatible with iTru primers is available at: http://baddna.uga.edu/tools-taggi.html. A fast and easy to use program to demultiplex amplicon pools with internal indexes is available at: https://github.com/lefeverde/Mr_Demuxy. |
One Health: A new definition for a sustainable and healthy future.
Adisasmito WB , Almuhairi S , Behravesh CB , Bilivogui P , Bukachi SA , Casas N , Cediel Becerra N , Charron DF , Chaudhary A , Ciacci Zanella JR , Cunningham AA , Dar O , Debnath N , Dungu B , Farag E , Gao GF , Hayman DTS , Khaitsa M , Koopmans MPG , Machalaba C , Mackenzie JS , Markotter W , Mettenleiter TC , Morand S , Smolenskiy V , Zhou L . PLoS Pathog 2022 18 (6) e1010537 The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic once more demonstrated the close connection between humans, animals, and the shared environment. Although still under investigation, the closest relatives of this virus exist in animals, and the factors leading to spillover remain to be fully understood. This interconnectedness again highlighted the need for a One Health approach. Although the One Health concept is not new and has been at the forefront of interdisciplinary and multisectoral discussions for years, there is now an increased interest for this approach to be applied and translated into action. Following a proposal made by the French and German Ministers for Foreign Affairs at the November 2020 Paris Peace Forum, 4 global partners, the Food and Agriculture Organization (FAO), the World Organization for Animal Health (OIE), the United Nations Environment Programme (UNEP), and the World Health Organization (WHO), in May 2021 established the interdisciplinary One Health High-Level Expert Panel (OHHLEP) (https://www.who.int/groups/one-health-high-level-expert-panel) to enhance their cross-sectoral collaboration. The creation of OHHLEP represents a recognition at the highest level of the urgency and complexities surrounding One Health and the intent to take this concept forward into policies and concrete actions. |
Fatal Human Rabies Infection with Suspected Host-mediated Failure of Post-Exposure Prophylaxis Following a Recognized Zoonotic Exposure-Minnesota, 2021.
Holzbauer SM , Schrodt CA , Prabhu RM , Asch-Kendrick RJ , Ireland M , Klumb C , Firestone MJ , Liu G , Harry K , Ritter JM , Levine MZ , Orciari LA , Wilkins K , Yager P , Gigante CM , Ellison JA , Zhao H , Niezgoda M , Li Y , Levis R , Scott D , Satheshkumar PS , Petersen BW , Rao AK , Bell WR , Bjerk SM , Forrest S , Gao W , Dasheiff R , Russell K , Pappas M , Kiefer J , Bickler W , Wiseman A , Jurantee J , Reichard RR , Smith KE , Lynfield R , Scheftel J , Wallace RM , Bonwitt J . Clin Infect Dis 2023 77 (8) 1201-1208 BACKGROUND: No rabies post-exposure prophylaxis (PEP) failure has been documented in humans in the United States using modern cell-culture vaccines. In January 2021, an 84-year-old male died from rabies six months after being bitten by a rabid bat despite receiving timely rabies post-exposure prophylaxis (PEP). We investigated the cause of breakthrough infection. METHODS: We reviewed medical records, laboratory results, and autopsy findings, and performed whole genome sequencing (WGS) to compare patient and bat virus sequences. Storage, administration, and integrity of PEP biologics administered to the patient were assessed; samples from leftover rabies immunoglobulin were evaluated for potency. We conducted risk assessments for persons potentially exposed to the bat and for close contacts of the patient. RESULTS: Rabies virus antibodies present in serum and cerebrospinal fluid were non-neutralizing. Antemortem blood testing revealed the patient had unrecognized monoclonal gammopathy of unknown significance. Autopsy findings showed rabies meningoencephalitis and metastatic prostatic adenocarcinoma. Rabies virus sequences from the patient and the offending bat were identical by WGS. No deviations were identified in potency, quality control, administration, or storage of administered PEP. Of 332 persons assessed for potential rabies exposure to the case patient, three (0.9%) warranted PEP. CONCLUSION: This is the first reported failure of rabies PEP in the Western Hemisphere using a cell culture vaccine. Host-mediated primary vaccine failure attributed to previously unrecognized impaired immunity is the most likely explanation for this breakthrough infection. Clinicians should consider measuring rabies neutralizing antibody titers after completion of PEP if there is any suspicion for immunocompromise. |
Industry, occupation, and exposure history of mesothelioma patients in the U.S. National Mesothelioma Virtual Bank, 2006-2022
Gao Y , Mazurek JM , Li Y , Blackley D , Weissman DN , Burton SV , Amin W , Landsittel D , Becich MJ , Ye Y . Environ Res 2022 230 115085 BACKGROUND: Malignant mesothelioma is associated with environmental and occupational exposure to certain mineral fibers, especially asbestos. This study aims to examine work histories of mesothelioma patients and their survival time. METHOD: Using the NIOSH Industry and Occupation Computerized Coding System, we mapped occupations and industries recorded for 748 of 1444 patients in the U.S. National Mesothelioma Virtual Bank (NMVB) during the period 2006-2022. Descriptive and survival analyses were conducted. RESULTS: Among the 1023 industries recorded for those having mesothelioma, the most frequent cases were found for those in manufacturing (n = 225, 22.0%), construction (138, 13.5%), and education services (66, 6.5%); among the 924 occupation records, the most frequent cases were found for those in construction and extraction (174, 18.8%), production (145, 15.7%), and management (84, 9.1%). Males (583) or persons aged >40 years (658) at the time of diagnosis tended to have worked in industries traditionally associated with mesothelioma (e.g., construction), while females (163) or persons aged 20-40 years (27) tended to have worked in industries not traditionally associated with mesothelioma (e.g., health care). Asbestos, unknown substances, and chemical solvents were the most frequently reported exposure, with females most often reporting an unknown substance. A multi-variable Cox Hazard Regression analysis showed that significant prognostic factors associated with decreased survival in mesothelioma cases are sex (male) and work experience in utility-related industry, while factor associated with increased survival are epithelial or epithelioid histological type, prior history of surgery and immunotherapy, and industry experience in accommodation and food services. CONCLUSION: The NMVB has the potential of serving as a sentinel surveillance mechanism for identifying industries and occupations not traditionally associated with mesothelioma. Results indicate the importance of considering all potential sources of asbestos exposures including occupational, environmental, and extra-occupational exposures when evaluating mesothelioma patients and advising family members. |
Household transmission dynamics of seasonal human coronaviruses
Quandelacy TM , Hitchings MDT , Lessler J , Read JM , Vukotich C , Azman AS , Salje H , Zimmer S , Gao H , Zheteyeva Y , Uzicanin A , Cummings DAT . J Infect Dis 2022 227 (9) 1104-1112 BACKGROUND: Household transmission studies inform how viruses spread among close contacts, but few characterize household transmission of endemic coronaviruses. METHODS: We used data collected from 223 households with school-age children participating in weekly disease surveillance over two respiratory virus seasons (December 2015 to May 2017), to describe clinical characteristics of endemic human coronaviruses (HCoV-229E, HCoV-HKU1, HCoV-NL63, HCoV-OC43) infections, and community and household transmission probabilities using a chain-binomial model correcting for missing data from untested households. RESULTS: Among 947 participants in 223 households, we observed 121 infections during the study, most commonly subtype HCoV-OC43. Higher proportions of infected children (<19y) displayed ILI symptoms than infected adults (relative risk 3.0, 95% credible interval (CrI) 1.5, 6.9). The estimated weekly household transmission probability was 9% (95% CrI 6, 13) and weekly community acquisition probability was 7% (95% CrI 5, 10). We found no evidence for differences in community or household transmission probabilities by age or symptom status. Simulations suggest that our study was underpowered to detect such differences. CONCLUSION: Our study highlights the need for large household studies to inform household transmission, the challenges in estimating household transmission probabilities from asymptomatic individuals, and implications for controlling endemic CoVs. |
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