Last data update: Jan 27, 2025. (Total: 48650 publications since 2009)
Records 1-30 (of 105 Records) |
Query Trace: Shen J[original query] |
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Vaccination should be everyone's business: Challenges in vaccinating pregnant women against influenza in the Republic of Moldova
Shen AK , Gutu V , Druc A , Capcelea A , Ebama M , Adams B , Belayneh A , Valleau M , Paraschiv A . Int J Gynaecol Obstet 2024 |
An evaluation of the National Influenza Vaccination Program in the Republic of Moldova, 2023-2024
Shen AK , Gutu V , Druc A , Ebama M , Belayneh A , Adams B , Valleau M , Paraschiv A . Vaccine 2024 42 (26) 126322 During the 2023-2024 influenza season, the Republic of Moldova, a lower-middle income country seeking accession into the European Union, independently financed their influenza vaccine supply transitioning from external support from the Partnership for International Vaccine Initiatives, a collaboration conceived in 2015. As part of this transition, a mixed-methods evaluation was conducted from May 2023 - January 2024 to identify current strengths and weaknesses of the influenza vaccination program. A total of 157 interviews were conducted: one with the National Immunization Program (NIP), six with district health officers, 18 at health facilities, 18 with caregivers/parents, 34 with healthcare workers, 43 with adults with chronic diseases, 19 with pregnant women, and 13 vaccine observation sessions; further five expert interviews with an international organization, the insurance company, senior government officials in public health and within the ministry of health, and those involved with COVID-19 were conducted. The Republic of Moldova's NIP has benefited from decades of experience, internal commitments to progress, and contributions from external partners. Despite this progress, the evaluation recognized four areas for improvement. Recommendations from the evaluation assessment included: 1) develop a national strategy for immunization, including the establishment of national goals in consultation with the national immunization technical advisory group (NITAG); 2) expand immunization communications and advocacy initiatives, particularly to adults and pregnant individuals; 3) leverage trusted patient-doctor relationships and encourage vaccination as a healthcare norm with physician specialists; and 4) conduct operations research to better understand vaccine hesitancy in populations such as pregnant individuals. Additional thematic findings emphasized the importance of ensuring timely receipt of vaccine doses into the country no later than September, as medical providers reported difficulty administering doses when vaccines were delivered after September. Our findings outline ways to further strengthen the Republic of Moldova's self-sustained annual influenza vaccination program. |
Antivirals for post-exposure prophylaxis of influenza: a systematic review and network meta-analysis
Zhao Y , Gao Y , Guyatt G , Uyeki TM , Liu P , Liu M , Shen Y , Chen X , Luo S , Li X , Huang R , Hao Q . Lancet 2024 404 (10454) 764-772 BACKGROUND: Antiviral post-exposure prophylaxis with neuraminidase inhibitors can reduce the incidence of influenza and the risk of symptomatic influenza, but the efficacy of the other classes of antiviral remains unclear. To support an update of WHO influenza guidelines, this systematic review and network meta-analysis evaluated antiviral drugs for post-exposure prophylaxis of influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023 that evaluated the efficacy and safety of antivirals compared with another antiviral or placebo or standard care for prevention of influenza. Pairs of reviewers independently screened studies, extracted data, and assessed the risk of bias. We performed network meta-analyses with frequentist random effects model and assessed the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. The outcomes of interest were symptomatic or asymptomatic infection, admission to hospital, all-cause mortality, adverse events related to antivirals, and serious adverse events. This study is registered with PROSPERO, CRD42023466450. FINDINGS: Of 11 845 records identified by our search, 33 trials of six antivirals (zanamivir, oseltamivir, laninamivir, baloxavir, amantadine, and rimantadine) that enrolled 19 096 individuals (mean age 6·75-81·15 years) were included in this systematic review and network meta-analysis. Most of the studies were rated as having a low risk of bias. Zanamivir, oseltamivir, laninamivir, and baloxavir probably achieve important reductions in symptomatic influenza in individuals at high risk of severe disease (zanamivir: risk ratio 0·35, 95% CI 0·25-0·50; oseltamivir: 0·40, 0·26-0·62; laninamivir: 0·43, 0·30-0·63; baloxavir: 0·43, 0·23-0·79; moderate certainty) when given promptly (eg, within 48 h) after exposure to seasonal influenza. These antivirals probably do not achieve important reductions in symptomatic influenza in individuals at low risk of severe disease when given promptly after exposure to seasonal influenza (moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir might achieve important reductions in symptomatic zoonotic influenza in individuals exposed to novel influenza A viruses associated with severe disease in infected humans when given promptly after exposure (low certainty). Oseltamivir, laninamivir, baloxavir, and amantadine probably decrease the risk of all influenza (symptomatic and asymptomatic infection; moderate certainty). Zanamivir, oseltamivir, laninamivir, and baloxavir probably have little or no effect on prevention of asymptomatic influenza virus infection or all-cause mortality (high or moderate certainty). Oseltamivir probably has little or no effect on admission to hospital (moderate certainty). All six antivirals do not significantly increase the incidence of drug-related adverse events or serious adverse events, although the certainty of evidence varies. INTERPRETATION: Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir probably decreases the risk of symptomatic seasonal influenza in individuals at high risk for severe disease after exposure to seasonal influenza viruses. Post-exposure prophylaxis with zanamivir, oseltamivir, laninamivir, or baloxavir might reduce the risk of symptomatic zoonotic influenza after exposure to novel influenza A viruses associated with severe disease in infected humans. FUNDING: World Health Organization. |
Antivirals for treatment of severe influenza: a systematic review and network meta-analysis of randomised controlled trials
Gao Y , Guyatt G , Uyeki TM , Liu M , Chen Y , Zhao Y , Shen Y , Xu J , Zheng Q , Li Z , Zhao W , Luo S , Chen X , Tian J , Hao Q . Lancet 2024 404 (10454) 753-763 BACKGROUND: The optimal antiviral drug for treatment of severe influenza remains unclear. To support updated WHO influenza clinical guidelines, this systematic review and network meta-analysis evaluated antivirals for treatment of patients with severe influenza. METHODS: We systematically searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Cumulative Index to Nursing and Allied Health Literature, Global Health, Epistemonikos, and ClinicalTrials.gov for randomised controlled trials published up to Sept 20, 2023, that enrolled hospitalised patients with suspected or laboratory-confirmed influenza and compared direct-acting influenza antivirals against placebo, standard care, or another antiviral. Pairs of coauthors independently extracted data on study characteristics, patient characteristics, antiviral characteristics, and outcomes, with discrepancies resolved by discussion or by a third coauthor. Key outcomes of interest were time to alleviation of symptoms, duration of hospitalisation, admission to intensive care unit, progression to invasive mechanical ventilation, duration of mechanical ventilation, mortality, hospital discharge destination, emergence of antiviral resistance, adverse events, adverse events related to treatments, and serious adverse events. We conducted frequentist network meta-analyses to summarise the evidence and evaluated the certainty of evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. This study is registered with PROSPERO, CRD42023456650. FINDINGS: Of 11 878 records identified by our search, eight trials with 1424 participants (mean age 36-60 years for trials that reported mean or median age; 43-78% male patients) were included in this systematic review, of which six were included in the network meta-analysis. The effects of oseltamivir, peramivir, or zanamivir on mortality compared with placebo or standard care without placebo for seasonal and zoonotic influenza were of very low certainty. Compared with placebo or standard care, we found low certainty evidence that duration of hospitalisation for seasonal influenza was reduced with oseltamivir (mean difference -1·63 days, 95% CI -2·81 to -0·45) and peramivir (-1·73 days, -3·33 to -0·13). Compared with standard care, there was little or no difference in time to alleviation of symptoms with oseltamivir (0·34 days, -0·86 to 1·54; low certainty evidence) or peramivir (-0·05 days, -0·69 to 0·59; low certainty evidence). There were no differences in adverse events or serious adverse events with oseltamivir, peramivir, and zanamivir (very low certainty evidence). Uncertainty remains about the effects of antivirals on other outcomes for patients with severe influenza. Due to the small number of eligible trials, we could not test for publication bias. INTERPRETATION: In hospitalised patients with severe influenza, oseltamivir and peramivir might reduce duration of hospitalisation compared with standard care or placebo, although the certainty of evidence is low. The effects of all antivirals on mortality and other important patient outcomes are very uncertain due to scarce data from randomised controlled trials. FUNDING: World Health Organization. |
Mixtures of urinary phenol and phthalate metabolite concentrations in relation to serum lipid levels among pregnant women: Results from the EARTH Study
Shen X , Génard-Walton M , Williams PL , James-Todd T , Ford JB , Rexrode KM , Calafat AM , Zhang D , Chavarro JE , Hauser R , Mínguez-Alarcón L , The Earth Study Team . Toxics 2024 12 (8) ![]() ![]() We examined whether mixtures of urinary concentrations of bisphenol A (BPA), parabens and phthalate metabolites were associated with serum lipid levels among 175 pregnant women who enrolled in the Environment and Reproductive Health (EARTH) Study (2005-2017), including triglycerides, total cholesterol, high-density lipoprotein (HDL), non-HDL, and low-density lipoprotein (LDL). We applied Bayesian Kernel Machine Regression (BKMR) and quantile g-computation while adjusting for confounders. In the BKMR models, we found no associations between chemical mixture and lipid levels, e.g., total cholesterol [mean difference (95% CRI, credible interval) = 0.02 (-0.31, 0.34)] and LDL [mean difference (95% CRI) = 0.10 (-0.22, 0.43)], when comparing concentrations at the 75th to the 25th percentile. When stratified by BMI, we found suggestive positive relationships between urinary propylparaben and total cholesterol and LDL among women with high BMI [mean difference (95% CRI) = 0.25 (-0.26, 0.75) and 0.35 (-0.25, 0.95)], but not with low BMI [mean difference (95% CRI) = 0.00 (-0.06, 0.07) and 0.00 (-0.07, 0.07)]. No association was found by quantile g-computation. This exploratory study suggests mixtures of phenol and phthalate metabolites were not associated with serum lipid levels during pregnancy, while there were some suggestive associations for certain BMI subgroups. Larger longitudinal studies with multiple assessments of both exposure and outcome are needed to corroborate these novel findings. |
An updated framework for SARS-CoV-2 variants reflects the unpredictability of viral evolution
Subissi L , Otieno JR , Worp N , Attar Cohen H , Oude Munnink BB , Abu-Raddad LJ , Alm E , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Ghedin E , Grant R , Haagmans BL , Happi C , Herring BL , Hodcroft EB , Ikejezie J , Katawera V , Kassamali ZA , Leo YS , Leung GM , Kondor RJ , Marklewitz M , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Naindoo D , Oh DY , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Saha S , Shen Y , Siqueira MM , Volz E , Tessema SK , Thiel V , Triki H , van der Werf S , von Eije K , Cunningham J , Koopmans MPG , von Gottberg A , Agrawal A , Van Kerkhove MD . Nat Med 2024 ![]() ![]() |
Genetics and genomics for the prevention and treatment of cardiovascular disease: update: a scientific statement from the American Heart Association.
Ganesh SK , Arnett DK , Assimes TL , Basson CT , Chakravarti A , Ellinor PT , Engler MB , Goldmuntz E , Herrington DM , Hershberger RE , Hong Y , Johnson JA , Kittner SJ , McDermott DA , Meschia JF , Mestroni L , O'Donnell CJ , Psaty BM , Vasan RS , Ruel M , Shen WK , Terzic A , Waldman SA . Circulation 2013 128 (25) 2813-51 ![]() Cardiovascular diseases (CVDs) are a major source of morbidity and mortality worldwide. Despite a decline of ≈30% over the past decade, heart disease remains the leading killer of Americans.1 For rare and familial forms of CVD, we are increasingly recognizing single-gene mutations that impart relatively large effects on individual phenotype. Examples include inherited forms of cardiomyopathy, arrhythmias, and aortic diseases. However, the prevalence of monogenic disorders typically accounts for a small proportion of the total CVD observed in the population. CVDs in the general population are complex diseases, with several contributing genetic and environmental factors. Although recent progress in monogenic disorders has occurred, we have seen a period of intense investigation to identify the genetic architecture of more common forms of CVD and related traits. | | Genomics serves several roles in cardiovascular health and disease, including disease prediction, discovery of genetic loci influencing CVD, functional evaluation of these genetic loci to understand mechanisms, and identification of therapeutic targets. For single-gene CVDs, progress has led to several clinically useful diagnostic tests, extending our ability to inform the management of afflicted patients and their family members. However, there has been little progress in developing genetic testing for complex CVD because individual common variants have only a modest impact on risk. The study of the genomics of complex CVDs is further challenged by the influence of environmental variables, phenotypic heterogeneity, and pathogenic complexity. Characterization of the clinical phenotype requires consideration of the clinical details of the diseases and traits under study. |
The Human Phenotype Ontology in 2024: phenotypes around the world
Gargano MA , Matentzoglu N , Coleman B , Addo-Lartey EB , Anagnostopoulos AV , Anderton J , Avillach P , Bagley AM , Bakštein E , Balhoff JP , Baynam G , Bello SM , Berk M , Bertram H , Bishop S , Blau H , Bodenstein DF , Botas P , Boztug K , Čady J , Callahan TJ , Cameron R , Carbon SJ , Castellanos F , Caufield JH , Chan LE , Chute CG , Cruz-Rojo J , Dahan-Oliel N , Davids JR , de Dieuleveult M , de Souza V , de Vries BBA , de Vries E , DePaulo JR , Derfalvi B , Dhombres F , Diaz-Byrd C , Dingemans AJM , Donadille B , Duyzend M , Elfeky R , Essaid S , Fabrizzi C , Fico G , Firth HV , Freudenberg-Hua Y , Fullerton JM , Gabriel DL , Gilmour K , Giordano J , Goes FS , Moses RG , Green I , Griese M , Groza T , Gu W , Guthrie J , Gyori B , Hamosh A , Hanauer M , Hanušová K , He YO , Hegde H , Helbig I , Holasová K , Hoyt CT , Huang S , Hurwitz E , Jacobsen JOB , Jiang X , Joseph L , Keramatian K , King B , Knoflach K , Koolen DA , Kraus ML , Kroll C , Kusters M , Ladewig MS , Lagorce D , Lai MC , Lapunzina P , Laraway B , Lewis-Smith D , Li X , Lucano C , Majd M , Marazita ML , Martinez-Glez V , McHenry TH , McInnis MG , McMurry JA , Mihulová M , Millett CE , Mitchell PB , Moslerová V , Narutomi K , Nematollahi S , Nevado J , Nierenberg AA , Čajbiková NN , Nurnberger JI Jr , Ogishima S , Olson D , Ortiz A , Pachajoa H , Perez de Nanclares G , Peters A , Putman T , Rapp CK , Rath A , Reese J , Rekerle L , Roberts AM , Roy S , Sanders SJ , Schuetz C , Schulte EC , Schulze TG , Schwarz M , Scott K , Seelow D , Seitz B , Shen Y , Similuk MN , Simon ES , Singh B , Smedley D , Smith CL , Smolinsky JT , Sperry S , Stafford E , Stefancsik R , Steinhaus R , Strawbridge R , Sundaramurthi JC , Talapova P , Tenorio Castano JA , Tesner P , Thomas RH , Thurm A , Turnovec M , van Gijn ME , Vasilevsky NA , Vlčková M , Walden A , Wang K , Wapner R , Ware JS , Wiafe AA , Wiafe SA , Wiggins LD , Williams AE , Wu C , Wyrwoll MJ , Xiong H , Yalin N , Yamamoto Y , Yatham LN , Yocum AK , Young AH , Yüksel Z , Zandi PP , Zankl A , Zarante I , Zvolský M , Toro S , Carmody LC , Harris NL , Munoz-Torres MC , Danis D , Mungall CJ , Köhler S , Haendel MA , Robinson PN . Nucleic Acids Res 2023 52 D1333-D1346 ![]() ![]() The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs. |
Pre-exposure prophylaxis uptake concerns in the Democratic Republic of the Congo: Key population and healthcare workers perspectives
Shen Y , Franks J , Reidy W , Olsen H , Wang C , Mushimbele N , Mazala RT , Tchissambou T , Malele F , Kilundu A , Bingham T , Djomand G , Mukinda E , Ewetola R , Abrams EJ , Teasdale CA . PLoS One 2023 18 (11) e0280977 Key populations (KP) in the Democratic Republic of the Congo (DRC), including female sex workers (SW), are disproportionally affected by HIV. Quantitative feedback surveys were conducted at seven health facilities in DRC with 70 KP clients enrolled in pre-exposure prophylaxis (PrEP) services to measure benefits and concerns. The surveys also assessed satisfaction with PrEP services and experiences of stigma at the health facilities. Thirty healthcare workers (HCW) were surveyed to measure attitudes, beliefs, and acceptability of providing services to KP. KP client survey participants were primarily female SW. KP clients reported that the primary concern about taking PrEP was fear of side effects (67%) although few KP reported having experienced side effect (14%). HCW concurred with clients that experienced and anticipated side effects were a primary PrEP uptake concern, along with costs of clinic visits. |
Mapping SARS-CoV-2 antigenic relationships and serological responses
Wilks SH , Mühlemann B , Shen X , Türeli S , LeGresley EB , Netzl A , Caniza MA , Chacaltana-Huarcaya JN , Corman VM , Daniell X , Datto MB , Dawood FS , Denny TN , Drosten C , Fouchier RAM , Garcia PJ , Halfmann PJ , Jassem A , Jeworowski LM , Jones TC , Kawaoka Y , Krammer F , McDanal C , Pajon R , Simon V , Stockwell MS , Tang H , van Bakel H , Veguilla V , Webby R , Montefiori DC , Smith DJ . Science 2023 382 (6666) eadj0070 ![]() During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, multiple variants escaping preexisting immunity emerged, causing reinfections of previously exposed individuals. Here, we used antigenic cartography to analyze patterns of cross-reactivity among 21 variants and 15 groups of human sera obtained after primary infection with 10 different variants or after messenger RNA (mRNA)-1273 or mRNA-1273.351 vaccination. We found antigenic differences among pre-Omicron variants caused by substitutions at spike-protein positions 417, 452, 484, and 501. Quantifying changes in response breadth over time and with additional vaccine doses, our results show the largest increase between 4 weeks and >3 months after a second dose. We found changes in immunodominance of different spike regions, depending on the variant an individual was first exposed to, with implications for variant risk assessment and vaccine-strain selection. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Koralov S , Wu B , Yeung S , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal S , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman D , Heguy A , Uyeki T , Clemente J , de Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst C , Koide S , Stapleford K , Khanna K , Ghedin E , Weiden M , Segal L . Res Sq 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
Microbial signatures in the lower airways of mechanically ventilated COVID19 patients associated with poor clinical outcome (preprint)
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Perez-Perez L , Jour G , Shen G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Hegu A , Evans L , Uyeki TM , Clemente JC , De Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . medRxiv 2021 Mortality among patients with COVID-19 and respiratory failure is high and there are no known lower airway biomarkers that predict clinical outcome. We investigated whether bacterial respiratory infections and viral load were associated with poor clinical outcome and host immune tone. We obtained bacterial and fungal culture data from 589 critically ill subjects with COVID-19 requiring mechanical ventilation. On a subset of the subjects that underwent bronchoscopy, we also quantified SARS-CoV-2 viral load, analyzed the microbiome of the lower airways by metagenome and metatranscriptome analyses and profiled the host immune response. We found that isolation of a hospital-acquired respiratory pathogen was not associated with fatal outcome. However, poor clinical outcome was associated with enrichment of the lower airway microbiota with an oral commensal ( Mycoplasma salivarium ), while high SARS-CoV-2 viral burden, poor anti-SARS-CoV-2 antibody response, together with a unique host transcriptome profile of the lower airways were most predictive of mortality. Collectively, these data support the hypothesis that 1) the extent of viral infectivity drives mortality in severe COVID-19, and therefore 2) clinical management strategies targeting viral replication and host responses to SARS-CoV-2 should be prioritized. |
An epitope-resurfaced virus-like particle can induce broad neutralizing antibody against four serotypes of dengue virus (preprint)
Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR , Chao DY . bioRxiv 2018 351700 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. Virus-like particles (VLPs) containing flavivirus prM/E proteins have been demonstrated to be a potential vaccine candidate; however, the structure of dengue VLP is poorly understood. Herein we show for the first time that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes through cryo-electron microscopy reconstruction. Mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher cross reactive (CR) neutralization antibodies (NtAbs) and were protected against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. Our results revealed that a “epitope-resurfaced” mature-form dengue VLP has the potential to induce quaternary structure-recognizing broad CR NtAbs. |
A dengue monovalent vaccine with novel structure provides cross-protection against four serotypes of dengue virus (preprint)
Chao DY , Shen WF , Galula JU , Liu JH , Liao MY , Huang CH , Wang YC , Wu HC , Liang JJ , Lin YL , Whitney MT , Chang GJ , Chen SR , Wu SR . bioRxiv 2018 275685 Dengue fever is caused by four different serotypes of dengue virus (DENV) which is the leading cause of worldwide arboviral diseases in humans. The vaccine candidates under development require a tetravalent immunogen to induce a balanced immunity against all four serotypes of dengue virus. Herein we show that mice vaccinated with highly matured virus-like particles derived from DENV serotype 2 (mD2VLP) can generate higher and broader neutralization antibodies (NtAbs) against all 4 serotypes of DENV through clonal expansion supported by hybridoma and B-cell repertoire analysis. The cryo-electron microscopy reconstruction showed that mD2VLP particles possess a T=1 icosahedral symmetry with a groove located within the E-protein dimers near the 2-fold vertices that exposed highly overlapping, cryptic neutralizing epitopes. Most importantly, maternally transferred antibodies derived from mD2VLP-vaccinated female mice protected suckling mice from lethal challenge by all four serotypes of DENV. Our results support the fact that a universal dengue vaccine that protects against all four serotypes of dengue viruses can be achieved by using an immunogen such as mD2VLP. |
Pre-exposure Prophylaxis Uptake Concerns in the Democratic Republic of the Congo: Key Population and Healthcare Workers Perspectives (preprint)
Shen Y , Franks J , Reidy W , Olsen H , Wang C , Mushimbele N , Mazala RT , Tchissambou T , Malele F , Kilundu A , Bingham T , Djomand G , Mukinda E , Ewetola R , Abrams EJ , Teasdale CA . medRxiv 2023 17 Key populations (KP) in the Democratic Republic of the Congo (DRC), including female sex workers (FSW), are disproportionally affected by HIV. Quantitative feedback surveys were conducted at seven health facilities in DRC with 70 KP clients enrolled in services to measure pre-exposure prophylaxis (PrEP) benefits and concerns. The surveys also assessed satisfaction with PrEP services and experiences of stigma at the health facilities. Thirty healthcare workers (HCW) were surveyed to measure attitudes, beliefs, and acceptability of providing services to KP. KP client survey participants were primarily female SW. KP clients reported that the primary concern about taking PrEP was fear of side effects. HCW concurred with clients that experienced and anticipated side effects were a primary PrEP uptake concern, along with costs of clinic visits. 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. |
Association of Mycobacterium tuberculosis infection test results with risk factors for tuberculosis transmission
Venkatappa T , Shen D , Ayala A , Li R , Sorri Y , Punnoose R , Katz D . J Clin Tuberc Other Mycobact Dis 2023 33 100386 BACKGROUND: Close contacts infected with Mycobacterium tuberculosis are at high risk of tuberculosis (TB) disease and a priority for preventive treatment. Three tests measure infection: two interferon-gamma release assays (IGRAs) and the tuberculin skin test (TST). The objective of our study was to assess the association of positive test results in contacts with infectiousness of the presumed TB source case. METHODS: Contacts in a cohort study at 10 United States sites received both IGRAs (QuantiFERON-TB Gold In-Tube (QFT-GIT) and T-SPOT.TB (T-SPOT)) and TST. We defined test conversion as negative for all tests at baseline and positive for at least one on retest. Risk ratios (RR) and 95% confidence intervals (CI) assessed association of positive test results with increased infectiousness of the TB case-defined as acid-fast bacilli (AFB) on sputum microscopy or cavities on chest radiographs- and contact demographics. RESULTS: Adjusted for contacts' age, nativity, sex, and race, IGRAs (QFT-GIT RR = 6.1, 95% CI 1.7-22.2; T-SPOT RR = 9.4, 95% CI 1.1-79.1), but not TST (RR = 1.7, 95% CI 0.8-3.7), were more likely to convert among contacts exposed to persons with cavitary TB disease. CONCLUSIONS: Because IGRA conversions in contacts are associated with infectiousness of the TB case, their use may improve efficiency of health department contact investigations by focusing efforts on those likely to benefit from preventive treatment in the United States. |
Cyclospora cayetanensis comprises at least three species that cause human cyclosporiasis
Barratt JLN , Shen J , Houghton K , Richins T , Sapp SGH , Cama V , Arrowood MJ , Straily A , Qvarnstrom Y . Parasitology 2023 150 (3) 269-285 ![]() The apicomplexan parasite Cyclospora cayetanensis causes seasonal foodborne outbreaks of the gastrointestinal illness cyclosporiasis. Prior to the coronavirus disease-2019 pandemic, annually reported cases were increasing in the USA, leading the US Centers for Disease Control and Prevention to develop a genotyping tool to complement cyclosporiasis outbreak investigations. Thousands of US isolates and 1 from China (strain CHN_HEN01) were genotyped by Illumina amplicon sequencing, revealing 2 lineages (A and B). The allelic composition of isolates was examined at each locus. Two nuclear loci (CDS3 and 360i2) distinguished lineages A and B. CDS3 had 2 major alleles: 1 almost exclusive to lineage A and the other to lineage B. Six 360i2 alleles were observed 2 exclusive to lineage A (alleles A1 and A2), 2 to lineage B (B1 and B2) and 1 (B4) was exclusive to CHN_HEN01 which shared allele B3 with lineage B. Examination of heterozygous genotypes revealed that mixtures of A- and B-type 360i2 alleles occurred rarely, suggesting a lack of gene flow between lineages. Phylogenetic analysis of loci from whole-genome shotgun sequences, mitochondrial and apicoplast genomes, revealed that CHN_HEN01 represents a distinct lineage (C). Retrospective examination of epidemiologic data revealed associations between lineage and the geographical distribution of US infections plus strong temporal associations. Given the multiple lines of evidence for speciation within human-infecting Cyclospora, we provide an updated taxonomic description of C. cayetanensis, and describe 2 novel species as aetiological agents of human cyclosporiasis: Cyclospora ashfordi sp. nov. and Cyclospora henanensis sp. nov. (Apicomplexa: Eimeriidae). |
Multistate outbreak of salmonella thompson infections linked to seafood exposure - United States, 2021
Shen AQ , Dalen A , Bankers L , Matzinger SR , Schwensohn C , Patel K , Hise KB , Pereira E , Cripe J , Jervis RH . MMWR Morb Mortal Wkly Rep 2023 72 (19) 513-516 ![]() ![]() In July 2021, the Colorado Department of Public Health and Environment (CDPHE) laboratory identified a cluster of five Salmonella enterica serotype Thompson isolates related to one another within one allele difference, using whole genome multilocus sequence typing (wgMLST). These five isolates, submitted to the public health laboratory as is routine process for confirmatory testing of Salmonella, were highly related to those identified in a 2020 multistate investigation, during which traceback was conducted for sushi-grade tuna and salmon; a common supplier was not identified. The 2021 investigation commenced on August 5, 2021, with five patients living in Colorado, and one each in Missouri, Washington, and Wisconsin. During August-December 2021, CDC, CDPHE, public health and regulatory officials in several states, and the Food and Drug Administration (FDA) conducted epidemiologic, environmental, and laboratory investigations of this multistate outbreak of Salmonella Thompson. Isolates were genetically related to one another and to 2020 isolates within zero to one allele difference. Implicated seafood products were traced to a single seafood distributor, in which the outbreak strain was identified through environmental sampling, and in which inspection identified inadequate sanitization and opportunities for cross-contamination of raw fish. The distributor issued a voluntary recall of 16 seafood items with high potential for contamination and completed remediation actions. This outbreak illustrated the importance of effective cleaning and sanitizing procedures and implementation of controls. When multiple products are recalled during an outbreak investigation, collaboration between public health agencies and implicated facilities can help provide food safety information to restaurants, retailers, and consumers, and to ensure disposal of all recalled products. |
Validity of administrative claims and electronic health registry data from a single practice for eye health surveillance
Wittenborn JS , Lee AY , Lundeen EA , Lamuda P , Saaddine J , Su GL , Lu R , Damani A , Zawadzki JS , Froines CP , Shen JZ , Kung TH , Yanagihara RT , Maring M , Takahashi MM , Blazes M , Rein DB . JAMA Ophthalmol 2023 IMPORTANCE: Diagnostic information from administrative claims and electronic health record (EHR) data may serve as an important resource for surveillance of vision and eye health, but the accuracy and validity of these sources are unknown. OBJECTIVE: To estimate the accuracy of diagnosis codes in administrative claims and EHRs compared to retrospective medical record review. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study compared the presence and prevalence of eye disorders based on diagnostic codes in EHR and claims records vs clinical medical record review at University of Washington-affiliated ophthalmology or optometry clinics from May 2018 to April 2020. Patients 16 years and older with an eye examination in the previous 2 years were included, oversampled for diagnosed major eye diseases and visual acuity loss. EXPOSURES: Patients were assigned to vision and eye health condition categories based on diagnosis codes present in their billing claims history and EHR using the diagnostic case definitions of the US Centers for Disease Control and Prevention Vision and Eye Health Surveillance System (VEHSS) as well as clinical assessment based on retrospective medical record review. MAIN OUTCOME AND MEASURES: Accuracy was measured as area under the receiver operating characteristic curve (AUC) of claims and EHR-based diagnostic coding vs retrospective review of clinical assessments and treatment plans. RESULTS: Among 669 participants (mean [range] age, 66.1 [16-99] years; 357 [53.4%] female), identification of diseases in billing claims and EHR data using VEHSS case definitions was accurate for diabetic retinopathy (claims AUC, 0.94; 95% CI, 0.91-0.98; EHR AUC, 0.97; 95% CI, 0.95-0.99), glaucoma (claims AUC, 0.90; 95% CI, 0.88-0.93; EHR AUC, 0.93; 95% CI, 0.90-0.95), age-related macular degeneration (claims AUC, 0.87; 95% CI, 0.83-0.92; EHR AUC, 0.96; 95% CI, 0.94-0.98), and cataracts (claims AUC, 0.82; 95% CI, 0.79-0.86; EHR AUC, 0.91; 95% CI, 0.89-0.93). However, several condition categories showed low validity with AUCs below 0.7, including diagnosed disorders of refraction and accommodation (claims AUC, 0.54; 95% CI, 0.49-0.60; EHR AUC, 0.61; 95% CI, 0.56-0.67), diagnosed blindness and low vision (claims AUC, 0.56; 95% CI, 0.53-0.58; EHR AUC, 0.57; 95% CI, 0.54-0.59), and orbital and external diseases (claims AUC, 0.63; 95% CI, 0.57-0.69; EHR AUC, 0.65; 95% CI, 0.59-0.70). CONCLUSION AND RELEVANCE: In this cross-sectional study of current and recent ophthalmology patients with high rates of eye disorders and vision loss, identification of major vision-threatening eye disorders based on diagnosis codes in claims and EHR records was accurate. However, vision loss, refractive error, and other broadly defined or lower-risk disorder categories were less accurately identified by diagnosis codes in claims and EHR data. |
Referrals of Infection Control Breaches to Public Health Authorities: Ambulatory Care Settings Experience, 2017
Braun BI , Chitavi SO , Perkins KM , Perz JF , Link-Gelles R , Hoppe J , Donofrio KM , Shen Y , Garcia-Houchins S . Jt Comm J Qual Patient Saf 2020 46 (9) 531-541 BACKGROUND: Beginning in October 2016, the Centers for Medicare & Medicaid Services (CMS) issued expanded guidance requiring accrediting organizations and state survey agencies to report serious infection control breaches to relevant state health departments. This project sought to characterize and summarize The Joint Commission's early experiences and findings in applying this guidance to facilities accredited under the ambulatory and office-based surgery programs in 2017. METHODS: Surveyor notes were retrospectively reviewed to identify individual breaches, and then the Centers for Disease Control and Prevention's Infection Prevention Checklist for Outpatient Settings was used to categorize and code documented breaches. RESULTS: Of 845 ambulatory organizations, 39 (4.6%) had breaches observed during the survey process and reported to health departments. Within these organizations, surveyors documented 356 breaches, representing 52 different breach codes. Common breach domains were sterilization of reusable devices, device reprocessing observation, device reprocessing, disinfection of reusable devices, and infection control program and infrastructure. Eight of the 39 facilities (20.5%) were cited for not performing the minimum level of reprocessing based on the items' intended use, reusing single-use devices, and/or not using aseptic technique to prepare injections. CONCLUSION: The CMS infection control breach reporting requirement has helped highlight some of the challenges faced by ambulatory facilities in providing a safe care environment for their patients. This analysis identified numerous opportunities for improved staff training and competencies as well as leadership oversight and investment in necessary resources. More systematic assessments of infection control practices, extending to both accredited and nonaccredited ambulatory facilities, are needed to inform oversight and prevention efforts. |
An early warning system for emerging SARS-CoV-2 variants.
Subissi L , von Gottberg A , Thukral L , Worp N , Oude Munnink BB , Rathore S , Abu-Raddad LJ , Aguilera X , Alm E , Archer BN , Attar Cohen H , Barakat A , Barclay WS , Bhiman JN , Caly L , Chand M , Chen M , Cullinane A , de Oliveira T , Drosten C , Druce J , Effler P , El Masry I , Faye A , Gaseitsiwe S , Ghedin E , Grant R , Haagmans BL , Herring BL , Iyer SS , Kassamali Z , Kakkar M , Kondor RJ , Leite JA , Leo YS , Leung GM , Marklewitz M , Moyo S , Mendez-Rico J , Melhem NM , Munster V , Nahapetyan K , Oh DY , Pavlin BI , Peacock TP , Peiris M , Peng Z , Poon LLM , Rambaut A , Sacks J , Shen Y , Siqueira MM , Tessema SK , Volz EM , Thiel V , van der Werf S , Briand S , Perkins MD , Van Kerkhove MD , Koopmans MPG , Agrawal A . Nat Med 2022 28 (6) 1110-1115 ![]() Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic. | | In June 2020, the World Health Organization (WHO) SARS-CoV-2 evolution working group was established to track SARS-CoV-2 variants and their specific genetic changes and to monitor viral characteristics and their impact on medical and non-medical countermeasures, including vaccines against COVID-19. In November 2021, this working group transitioned to a formal WHO Technical Advisory Group on Virus Evolution (TAG-VE), with the aim of developing and implementing a global risk-monitoring framework for SARS-CoV-2 variants, based on a multidisciplinary approach that includes in silico, virological, clinical and epidemiological data. |
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.). |
Comparing telephone survey responses to best-corrected visual acuity to estimate the accuracy of identifying vision loss: Validation study
Wittenborn J , Lee A , Lundeen EA , Lamuda P , Saaddine J , Su GL , Lu R , Damani A , Zawadzki JS , Froines CP , Shen JZ , Kung TH , Yanagihara RT , Maring M , Takahashi MM , Blazes M , Rein DB . JMIR Public Health Surveill 2023 9 e44552 BACKGROUND: Self-reported questions on blindness and vision problems are collected in many national surveys. Recently released surveillance estimates on the prevalence of vision loss used self-reported data to predict variation in the prevalence of objectively measured acuity loss among population groups for whom examination data are not available. However, the validity of self-reported measures to predict prevalence and disparities in visual acuity has not been established. OBJECTIVE: This study aimed to estimate the diagnostic accuracy of self-reported vision loss measures compared to best-corrected visual acuity (BCVA), inform the design and selection of questions for future data collection, and identify the concordance between self-reported vision and measured acuity at the population level to support ongoing surveillance efforts. METHODS: We calculated accuracy and correlation between self-reported visual function versus BCVA at the individual and population level among patients from the University of Washington ophthalmology or optometry clinics with a prior eye examination, randomly oversampled for visual acuity loss or diagnosed eye diseases. Self-reported visual function was collected via telephone survey. BCVA was determined based on retrospective chart review. Diagnostic accuracy of questions at the person level was measured based on the area under the receiver operator curve (AUC), whereas population-level accuracy was determined based on correlation. RESULTS: The survey question, "Are you blind or do you have serious difficulty seeing, even when wearing glasses?" had the highest accuracy for identifying patients with blindness (BCVA ≤20/200; AUC=0.797). The highest accuracy for detecting any vision loss (BCVA <20/40) was achieved by responses of "fair," "poor," or "very poor" to the question, "At the present time, would you say your eyesight, with glasses or contact lenses if you wear them, is excellent, good, fair, poor, or very poor" (AUC=0.716). At the population level, the relative relationship between prevalence based on survey questions and BCVA remained stable for most demographic groups, with the only exceptions being groups with small sample sizes, and these differences were generally not significant. CONCLUSIONS: Although survey questions are not considered to be sufficiently accurate to be used as a diagnostic test at the individual level, we did find relatively high levels of accuracy for some questions. At the population level, we found that the relative prevalence of the 2 most accurate survey questions were highly correlated with the prevalence of measured visual acuity loss among nearly all demographic groups. The results of this study suggest that self-reported vision questions fielded in national surveys are likely to yield an accurate and stable signal of vision loss across different population groups, although the actual measure of prevalence from these questions is not directly analogous to that of BCVA. |
Isolation and characterization of mammalian orthoreovirus from bats in the United States.
Wang L , Zheng B , Shen Z , Nath ND , Li Y , Walsh T , Li Y , Mitchell W , He D , Lee J , Moore S , Tong S , Zhang S , Ma W . J Med Virol 2023 95 (2) e28492 ![]() ![]() Mammalian orthoreovirus (MRV) infects many mammalian species including humans, bats, and domestic animals. To determine the prevalence of MRV in bats in the United States, we screened more than 900 bats of different species collected during 2015 to 2019 by a real-time RT-PCR assay; 4.4% bats tested MRV-positive and 13 MRVs were isolated. Sequence and phylogenetic analysis revealed that these isolates belonged to four different strains/genotypes of viruses in serotypes 1 or 2, which contain genes similar to those of MRVs detected in humans, bats, bovine, and deer. Further characterization showed that these four MRV strains replicated efficiently on human, canine, monkey, ferret and swine cell lines. The 40/Bat/USA/2018 strain belonging to the serotype 1 demonstrated the ability to infect and transmit in pigs without prior adaptation. Taken together, this is evidence for different genotypes and serotypes of MRVs circulating in U.S. bats, which can be a mixing vessel of MRVs that may spread to other species, including humans, resulting in cross-species infections. This article is protected by copyright. All rights reserved. |
Correction: Comparative outcomes for mature T and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomas
Koh MJ , Merrill MH , Koh MJ , Stuver R , Alonso CD , Foss FM , Mayor AM , Gill J , Epeldegui M , Cachay E , Thorne JE , Silverberg MJ , Horberg MA , Atlhoff KN , Nijhawan AE , McGinnis KA , Lee JS , Rabkin CS , Napravnik S , Li J , Castilho JL , Shen C , Jain S . Blood Adv 2022 6 (15) 4436 An author's name was misspelled in the byline on page 1420. “Keri N. Atlhoff” should read “Keri N. Althoff.” The error has been corrected in the published article. |
An improved workflow for accurate and robust healthcare environmental surveillance using metagenomics.
Shen J , McFarland AG , Blaustein RA , Rose LJ , Perry-Dow KA , Moghadam AA , Hayden MK , Young VB , Hartmann EM . Microbiome 2022 10 (1) 206 ![]() ![]() ![]() BACKGROUND: Effective surveillance of microbial communities in the healthcare environment is increasingly important in infection prevention. Metagenomics-based techniques are promising due to their untargeted nature but are currently challenged by several limitations: (1) they are not powerful enough to extract valid signals out of the background noise for low-biomass samples, (2) they do not distinguish between viable and nonviable organisms, and (3) they do not reveal the microbial load quantitatively. An additional practical challenge towards a robust pipeline is the inability to efficiently allocate sequencing resources a priori. Assessment of sequencing depth is generally practiced post hoc, if at all, for most microbiome studies, regardless of the sample type. This practice is inefficient at best, and at worst, poor sequencing depth jeopardizes the interpretation of study results. To address these challenges, we present a workflow for metagenomics-based environmental surveillance that is appropriate for low-biomass samples, distinguishes viability, is quantitative, and estimates sequencing resources. RESULTS: The workflow was developed using a representative microbiome sample, which was created by aggregating 120 surface swabs collected from a medical intensive care unit. Upon evaluating and optimizing techniques as well as developing new modules, we recommend best practices and introduce a well-structured workflow. We recommend adopting liquid-liquid extraction to improve DNA yield and only incorporating whole-cell filtration when the nonbacterial proportion is large. We suggest including propidium monoazide treatment coupled with internal standards and absolute abundance profiling for viability assessment and involving cultivation when demanding comprehensive profiling. We further recommend integrating internal standards for quantification and additionally qPCR when we expect poor taxonomic classification. We also introduce a machine learning-based model to predict required sequencing effort from accessible sample features. The model helps make full use of sequencing resources and achieve desired outcomes. Video Abstract CONCLUSIONS: This workflow will contribute to more accurate and robust environmental surveillance and infection prevention. Lessons gained from this study will also benefit the continuing development of methods in relevant fields. |
The effect of the body wake and operator motion on the containment of nanometer-scale airborne substances using a conventional fume hood and specially designed enclosing hood: a comparison using computational fluid dynamics
Shen C , Dunn KH , Woskie SR , Bennett JS , Ellenbecker MJ , Dandy DS , Tsai CSJ . J Nanopart Res 2022 24 (4) Airborne substances in the nanoparticle size range would mostly follow the primary airflow patterns, which emphasizes the importance of understanding the airflow dynamics to effectively control exposures to toxic airborne substances such as nanometer-sized particles. Chemical fume hoods are being utilized as primary controls for worker exposure to airborne substances including nanometer-scale materials due to their overall availability and history of effective contaminant. This study evaluates the impact of the body wake on the containment performance of a conventional constant air volume (CAV) and a new “nano” ventilated enclosing hood using numerical methods. Numerical studies have been performed to predict leaks of nanomaterials handled inside the hood. We further performed experiments in this study to validate the velocity fields predicted by the computational fluid dynamic (CFD) models and to provide a basis for evaluating the impact of the human body on fume hood containment performance. Using these validated models, the effects of the motion of the arms moving out of the hood were simulated using CFD to assess how one of the common actions of an operator/user may affect containment. Results of our simulations show that areas near the hood side airfoils and directly behind the sash are more likely to concentrate contaminants released inside the hood and potentially result in leakage based on internal airflow patterns. These areas are key to monitor when assessing fume hood containment along with the operator/mannequin breathing zone to get an understanding of potential leak areas which might contribute to operator exposure as well as exposure to others inside the laboratory. © 2022, The Author(s), under exclusive licence to Springer Nature B.V. |
Defining the risk of SARS-CoV-2 variants on immune protection.
DeGrace MM , Ghedin E , Frieman MB , Krammer F , Grifoni A , Alisoltani A , Alter G , Amara RR , Baric RS , Barouch DH , Bloom JD , Bloyet LM , Bonenfant G , Boon ACM , Boritz EA , Bratt DL , Bricker TL , Brown L , Buchser WJ , Carreo JM , Cohen-Lavi L , Darling TL , Davis-Gardner ME , Dearlove BL , Di H , Dittmann M , Doria-Rose NA , Douek DC , Drosten C , Edara VV , Ellebedy A , Fabrizio TP , Ferrari G , Florence WC , Fouchier RAM , Franks J , Garca-Sastre A , Godzik A , Gonzalez-Reiche AS , Gordon A , Haagmans BL , Halfmann PJ , Ho DD , Holbrook MR , Huang Y , James SL , Jaroszewski L , Jeevan T , Johnson RM , Jones TC , Joshi A , Kawaoka Y , Kercher L , Koopmans MPG , Korber B , Koren E , Koup RA , LeGresley EB , Lemieux JE , Liebeskind MJ , Liu Z , Livingston B , Logue JP , Luo Y , McDermott AB , McElrath MJ , Meliopoulos VA , Menachery VD , Montefiori DC , Mhlemann B , Munster VJ , Munt JE , Nair MS , Netzl A , Niewiadomska AM , O'Dell S , Pekosz A , Perlman S , Pontelli MC , Rockx B , Rolland M , Rothlauf PW , Sacharen S , Scheuermann RH , Schmidt SD , Schotsaert M , Schultz-Cherry S , Seder RA , Sedova M , Sette A , Shabman RS , Shen X , Shi PY , Shukla M , Simon V , Stumpf S , Sullivan NJ , Thackray LB , Theiler J , Thomas PG , Trifkovic S , Treli S , Turner SA , Vakaki MA , vanBakel H , VanBlargan LA , Vincent LR , Wallace ZS , Wang L , Wang M , Wang P , Wang W , Weaver SC , Webby RJ , Weiss CD , Wentworth DE , Weston SM , Whelan SPJ , Whitener BM , Wilks SH , Xie X , Ying B , Yoon H , Zhou B , Hertz T , Smith DJ , Diamond MS , Post DJ , Suthar MS . Nature 2022 605 (7911) 640-652 ![]() The global emergence of many severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants jeopardizes the protective antiviral immunity induced following infection or vaccination. To address the public health threat caused by the increasing SARS-CoV-2 genomic diversity, the National Institute of Allergy and Infectious Diseases (NIAID) within the National Institutes of Health (NIH) established the SARS-CoV-2 Assessment of Viral Evolution (SAVE) program. This effort was designed to provide a real-time risk assessment of SARS-CoV-2 variants potentially impacting transmission, virulence, and resistance to convalescent and vaccine-induced immunity. The SAVE program serves as a critical data-generating component of the United States Government SARS-CoV-2 Interagency Group to assess implications of SARS-CoV-2 variants on diagnostics, vaccines, and therapeutics and for communicating public health risk. Here we describe the coordinated approach used to identify and curate data about emerging variants, their impact on immunity, and effects on vaccine protection using animal models. We report the development of reagents, methodologies, models, and pivotal findings facilitated by this collaborative approach and identify future challenges. This program serves as a template for the response against rapidly evolving pandemic pathogens by monitoring viral evolution in the human population to identify variants that could erode the effectiveness of countermeasures. |
Comparative outcomes for mature T and NK/T-cell lymphomas in people with and without HIV and to AIDS-defining lymphomas
Koh MJ , Merrill MH , Koh MJ , Stuver R , Alonso CD , Foss FM , Mayor AM , Gill J , Epeldegui M , Cachay E , Thorne JE , Silverberg MJ , Horberg MA , Atlhoff KN , Nijhawan AE , McGinnis KA , Lee JS , Rabkin CS , Napravnik S , Li J , Castilho JL , Shen C , Jain S . Blood Adv 2022 6 (5) 1420-1431 There are no studies comparing the prognosis for mature T-cell lymphoma (TCL) in people with human immunodeficiency virus (PWH) to people without HIV (PWoH) and to AIDS-defining B-cell lymphomas (A-BCL) in the modern antiretroviral therapy (ART) era. NA-ACCORD and COMPLETE are cohorts that enroll patients diagnosed with HIV and TCL, respectively. In our study 52, 64, 101, 500 and 246 PWH with histological confirmation of TCL, primary CNS, Burkitt's, diffuse large B-cell lymphoma (DLBCL) and Hodgkin's lymphoma (HL) respectively and 450 TCL without HIV were eligible for analysis. At the time of TCL diagnosis, Anaplastic large-cell lymphoma (ALCL) was the most common TCL subtype within PWH. While PWH with TCL diagnosed between 1996-2009, experienced a low 5-year survival probability at 0.23 (95% CI: 0.13, 0.41), we observed a marked improvement in their survival when diagnosed between 2010-2016 (0.69; 95% CI: 0.48, 1; p=0.04) in contrast to TCL among PWoH (0.45; 95% CI: 0.41, 0.51; p=0.53). Similarly, PWH with ALCL diagnosed between 1996-2009 were associated with a conspicuously inferior 5-year survival probability (0.17; 95% CI: 0.07, 0.42) and consistently lagged behind A-BCL subtypes such as Burkitt's (0.43; 95% CI:0.33, 0.57; p=0.09) and DLBCL (0.17; 95% CI: 0.06, 0.46; p=0.11) and behind HL (0.57; 95% CI: 0.50, 0.65; p <0.0001). Despite a small number, those diagnosed between 2010-2016, experienced a remarkable improvement in survival (0.67; 95% CI: 0.3, 1) in comparison to PWoH (0.76; 95% CI: 0.66, 0.87; p=0.58). Thus, our analysis confirms improved overall survival for aggressive B and T-cell malignancies among PWH in the last decade. |
Microbial signatures in the lower airways of mechanically ventilated COVID-19 patients associated with poor clinical outcome.
Sulaiman I , Chung M , Angel L , Tsay JJ , Wu BG , Yeung ST , Krolikowski K , Li Y , Duerr R , Schluger R , Thannickal SA , Koide A , Rafeq S , Barnett C , Postelnicu R , Wang C , Banakis S , Pérez-Pérez L , Shen G , Jour G , Meyn P , Carpenito J , Liu X , Ji K , Collazo D , Labarbiera A , Amoroso N , Brosnahan S , Mukherjee V , Kaufman D , Bakker J , Lubinsky A , Pradhan D , Sterman DH , Weiden M , Heguy A , Evans L , Uyeki TM , Clemente JC , de Wit E , Schmidt AM , Shopsin B , Desvignes L , Wang C , Li H , Zhang B , Forst CV , Koide S , Stapleford KA , Khanna KM , Ghedin E , Segal LN . Nat Microbiol 2021 6 (10) 1245-1258 ![]() Respiratory failure is associated with increased mortality in COVID-19 patients. There are no validated lower airway biomarkers to predict clinical outcome. We investigated whether bacterial respiratory infections were associated with poor clinical outcome of COVID-19 in a prospective, observational cohort of 589 critically ill adults, all of whom required mechanical ventilation. For a subset of 142 patients who underwent bronchoscopy, we quantified SARS-CoV-2 viral load, analysed the lower respiratory tract microbiome using metagenomics and metatranscriptomics and profiled the host immune response. Acquisition of a hospital-acquired respiratory pathogen was not associated with fatal outcome. Poor clinical outcome was associated with lower airway enrichment with an oral commensal (Mycoplasma salivarium). Increased SARS-CoV-2 abundance, low anti-SARS-CoV-2 antibody response and a distinct host transcriptome profile of the lower airways were most predictive of mortality. Our data provide evidence that secondary respiratory infections do not drive mortality in COVID-19 and clinical management strategies should prioritize reducing viral replication and maximizing host responses to SARS-CoV-2. |
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