Last data update: May 06, 2024. (Total: 46732 publications since 2009)
Records 1-30 (of 447 Records) |
Query Trace: Lin J[original query] |
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Deployment of the National Notifiable Diseases Surveillance System during the 2022-23 mpox outbreak in the United States-Opportunities and challenges with case notifications during public health emergencies
Rainey JJ , Lin XM , Murphy S , Velazquez-Kronen R , Do T , Hughes C , Harris AM , Maitland A , Gundlapalli AV . PLoS One 2024 19 (4) e0300175 Timely case notifications following the introduction of an uncommon pathogen, such as mpox, are critical for understanding disease transmission and for developing and implementing effective mitigation strategies. When Massachusetts public health officials notified the Centers for Disease Control and Prevention (CDC) about a confirmed orthopoxvirus case on May 17, 2023, which was later confirmed as mpox at CDC, mpox was not a nationally notifiable disease. Because existing processes for new data collections through the National Notifiable Disease Surveillance System were not well suited for implementation during emergency responses at the time of the mpox outbreak, several interim notification approaches were established to capture case data. These interim approaches were successful in generating daily case counts, monitoring disease transmission, and identifying high-risk populations. However, the approaches also required several data collection approvals by the federal government and the Council for State and Territorial Epidemiologists, the use of four different case report forms, and the establishment of complex data management and validation processes involving data element mapping and record-level de-duplication steps. We summarize lessons learned from these interim approaches to inform and improve case notifications during future outbreaks. These lessons reinforce CDC's Data Modernization Initiative to work in close collaboration with state, territorial, and local public health departments to strengthen case-based surveillance prior to the next public health emergency. |
Reducing hospitalizations and multidrug-resistant organisms via regional decolonization in hospitals and nursing homes
Gussin GM , McKinnell JA , Singh RD , Miller LG , Kleinman K , Saavedra R , Tjoa T , Gohil SK , Catuna TD , Heim LT , Chang J , Estevez M , He J , O'Donnell K , Zahn M , Lee E , Berman C , Nguyen J , Agrawal S , Ashbaugh I , Nedelcu C , Robinson PA , Tam S , Park S , Evans KD , Shimabukuro JA , Lee BY , Fonda E , Jernigan JA , Slayton RB , Stone ND , Janssen L , Weinstein RA , Hayden MK , Lin MY , Peterson EM , Bittencourt CE , Huang SS . Jama 2024 IMPORTANCE: Infections due to multidrug-resistant organisms (MDROs) are associated with increased morbidity, mortality, length of hospitalization, and health care costs. Regional interventions may be advantageous in mitigating MDROs and associated infections. OBJECTIVE: To evaluate whether implementation of a decolonization collaborative is associated with reduced regional MDRO prevalence, incident clinical cultures, infection-related hospitalizations, costs, and deaths. DESIGN, SETTING, AND PARTICIPANTS: This quality improvement study was conducted from July 1, 2017, to July 31, 2019, across 35 health care facilities in Orange County, California. EXPOSURES: Chlorhexidine bathing and nasal iodophor antisepsis for residents in long-term care and hospitalized patients in contact precautions (CP). MAIN OUTCOMES AND MEASURES: Baseline and end of intervention MDRO point prevalence among participating facilities; incident MDRO (nonscreening) clinical cultures among participating and nonparticipating facilities; and infection-related hospitalizations and associated costs and deaths among residents in participating and nonparticipating nursing homes (NHs). RESULTS: Thirty-five facilities (16 hospitals, 16 NHs, 3 long-term acute care hospitals [LTACHs]) adopted the intervention. Comparing decolonization with baseline periods among participating facilities, the mean (SD) MDRO prevalence decreased from 63.9% (12.2%) to 49.9% (11.3%) among NHs, from 80.0% (7.2%) to 53.3% (13.3%) among LTACHs (odds ratio [OR] for NHs and LTACHs, 0.48; 95% CI, 0.40-0.57), and from 64.1% (8.5%) to 55.4% (13.8%) (OR, 0.75; 95% CI, 0.60-0.93) among hospitalized patients in CP. When comparing decolonization with baseline among NHs, the mean (SD) monthly incident MDRO clinical cultures changed from 2.7 (1.9) to 1.7 (1.1) among participating NHs, from 1.7 (1.4) to 1.5 (1.1) among nonparticipating NHs (group × period interaction reduction, 30.4%; 95% CI, 16.4%-42.1%), from 25.5 (18.6) to 25.0 (15.9) among participating hospitals, from 12.5 (10.1) to 14.3 (10.2) among nonparticipating hospitals (group × period interaction reduction, 12.9%; 95% CI, 3.3%-21.5%), and from 14.8 (8.6) to 8.2 (6.1) among LTACHs (all facilities participating; 22.5% reduction; 95% CI, 4.4%-37.1%). For NHs, the rate of infection-related hospitalizations per 1000 resident-days changed from 2.31 during baseline to 1.94 during intervention among participating NHs, and from 1.90 to 2.03 among nonparticipating NHs (group × period interaction reduction, 26.7%; 95% CI, 19.0%-34.5%). Associated hospitalization costs per 1000 resident-days changed from $64 651 to $55 149 among participating NHs and from $55 151 to $59 327 among nonparticipating NHs (group × period interaction reduction, 26.8%; 95% CI, 26.7%-26.9%). Associated hospitalization deaths per 1000 resident-days changed from 0.29 to 0.25 among participating NHs and from 0.23 to 0.24 among nonparticipating NHs (group × period interaction reduction, 23.7%; 95% CI, 4.5%-43.0%). CONCLUSIONS AND RELEVANCE: A regional collaborative involving universal decolonization in long-term care facilities and targeted decolonization among hospital patients in CP was associated with lower MDRO carriage, infections, hospitalizations, costs, and deaths. |
Determinants of type-specific human papillomavirus concordance across anatomic sites in young men who have sex with men and transgender women, 3 U.S. Cities, 2016-2018
Shah A , Meites E , Lin J , Hughes JP , Gorbach PM , Mustanski B , Crosby RA , Unger ER , Querec T , Golden M , Markowitz LE , Winer RL . Sex Transm Dis 2024 51 (4) 260-269 BACKGROUND: Among men who have sex with men (MSM) and transgender women (TGW), the dynamics of human papillomavirus (HPV) infections at different anatomical sites are not well understood. Information on HPV concordance between anatomic sites can inform the extent of autoinoculation, and susceptibility of different anatomic areas to HPV infection. We described and assessed correlates of HPV concordance across anal, oral, and genital samples. METHODS: We enrolled 1876 MSM and TGW aged 18 to 26 years in 3 US cities. Oral, genital, and anal samples were self-collected for type-specific HPV DNA testing (37 types). Demographics, sexual behaviors, and health history were self-reported. Kappa statistics based on percent positive agreement (kappa+) and generalized estimating equations were used to describe and identify correlates of HPV type-specific concordance between anatomic sample pairs. RESULTS: Any HPV was detected in 69.9%, 48.6%, and 7.4% of anal, genital, and oral samples, respectively. Detection of any HPV (concurrence) was most common in anal-genital pairs (40.9%) and uncommon in oral-genital and oral-anal pairs (3.4% and 6.5% respectively). Type-specific concordance was poor across all sample pairs (kappa+ <0.20). Younger age and older age at first sex were positively associated with type-concordant anal-genital infections. Sexual behaviors were unassociated with concordance. CONCLUSIONS: Poor oral/anogenital concordance suggests the oral mucosa has different susceptibility to HPV infection, differential clearance and/or autoinoculation between oral and anogenital sites is unlikely. There was some observed concurrence and concordance between anal and genital sites, unassociated with sexual behavior, suggesting autoinoculation. Longitudinal studies are necessary to further elucidate mechanisms of multisite infections. |
Microrna-mediated Krüppel-Like Factor 4 upregulation induces alternatively activated macrophage-associated marker and chemokine transcription in 4,4'-methylene diphenyl diisocyanate exposed macrophages
Lin CC , Law BF , Hettick JM . Xenobiotica 2024 1-22 Occupational exposure to 4,4'-methylene diphenyl diisocyanate (MDI) is associated with occupational asthma (OA) development. Alveolar macrophage-induced recruitment of immune cells to the lung microenvironment plays an important role during asthma pathogenesis. Previous studies identified that MDI/MDI-glutathione (GSH)-exposure downregulates endogenous hsa-miR-206-3p/hsa-miR-381-3p. Our prior report shows that alternatively activated (M2) macrophage-associated markers/chemokines are induced by MDI/MDI-GSH-mediated Krüppel-Like Factor 4 (KLF4) upregulation in macrophages and stimulates immune cell chemotaxis. However, the underlying molecular mechanism(s) by which MDI/MDI-GSH upregulates KLF4 remain unclear.Following MDI-GSH exposure, microRNA(miR)-inhibitors/mimics or plasmid transfection, endogenous hsa-miR-206-3p/hsa-miR-381-3p, KLF4, or M2 macrophage-associated markers (CD206, TGM2), and chemokines (CCL17, CCL22, CCL24) were measured by either RT-qPCR, western blot, or luciferase assay.MDI-GSH exposure downregulates hsa-miR-206-3p/hsa-miR-381-3p by 1.46- to 9.75-fold whereas upregulates KLF4 by 1.68- to 1.99-fold, respectively. In silico analysis predicts binding between hsa-miR-206-3p/hsa-miR-381-3p and KLF4. Gain- and loss-of-function, luciferase reporter assays and RNA-induced silencing complex-immunoprecipitation (RISC-IP) studies confirm the posttranscriptional regulatory roles of hsa-miR-206-3p/hsa-miR-381-3p and KLF4 in macrophages. Furthermore, hsa-miR-206-3p/hsa-miR-381-3p regulate the expression of M2 macrophage-associated markers and chemokines via KLF4.In conclusion, hsa-miR-206-3p/hsa-miR-381-3p play a major role in regulation of MDI/MDI-GSH-induced M2 macrophage-associated markers and chemokines by targeting the KLF4 transcript, and KLF4-mediated regulation in macrophages. |
"Waiving" Goodbye to PE: State Law and School Exemption and Substitution Practices in the United States
Chriqui JF , Leider J , Piekarz-Porter E , Lin W , Turner L , Michael SL , Brener N , Perna F . Transl J Am Coll Sports Med 12/28/2021 6 (2) PURPOSE: The importance of schools providing physical education (PE) and promoting physical activity (PA) and the benefits of PA for children are well documented. However, a majority of students do not get the nationally recommended 60 min of daily PA. Many states grant waivers, substitutions, or exemptions from PE despite national recommendations. This study examined the association between state laws allowing for the use of PE substitutions and exemptions and school-level substitution and exemption practices. METHODS: School-level PE exemption and substitution data from the 2014 School Health Policies and Practices Study were linked to state law data from the National Wellness Policy Study and the National Cancer Institute's 2013 Classification of Laws Associated with School Students. The analytic sample included 320 schools located in 42 states. Separate multivariable logistic regression models linked five types of school PE exemptions/substitutions to corresponding state laws, controlling for school characteristics. RESULTS: Overall, 24 of the 42 states had laws addressing PE waivers, exemptions, or substitutions. Schools had higher odds of allowing PE substitutions for school sports (adjusted odds ratio (AOR), 3.59; 95% confidence interval (CI), 1.33-9.68), other school activities (AOR, 8.52; 95% CI, 2.90-25.03), and community sports (AOR, 4.30; 95% CI, 1.43-12.96) and allowing exemptions for fitness test scores (AOR, 4.67; 95% CI, 1.49-14.62) or vocational training (AOR, 5.92; 95% CI, 1.04-33.68) if state law allowed it, compared with schools in states that did not allow such practices. CONCLUSIONS: Given the connection between PA and beneficial outcomes for children, decision makers, school administrators, practitioners, advocates, and researchers should consider and further examine how PE waiver, exemption, and substitution policies and practices may affect students' PA and related outcomes. |
Heterogeneity in measures of illness among patients with myalgic encephalomyelitis/chronic fatigue syndrome is not explained by clinical practice: A study in seven U.S. Specialty clinics
Unger ER , Lin JMS , Chen Y , Cornelius ME , Helton B , Issa AN , Bertolli J , Klimas NG , Balbin EG , Bateman L , Lapp CW , Springs W , Podell RN , Fitzpatrick T , Peterson DL , Gottschalk CG , Natelson BH , Blate M , Kogelnik AM , Phan CC . J Clin Med 2024 13 (5) Background: One of the goals of the Multi-site Clinical Assessment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (MCAM) study was to evaluate whether clinicians experienced in diagnosing and caring for patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) recognized the same clinical entity. Methods: We enrolled participants from seven specialty clinics in the United States. We used baseline data (n = 465) on standardized questions measuring general clinical characteristics, functional impairment, post-exertional malaise, fatigue, sleep, neurocognitive/autonomic symptoms, pain, and other symptoms to evaluate whether patient characteristics differed by clinic. Results: We found few statistically significant and no clinically significant differences between clinics in their patients’ standardized measures of ME/CFS symptoms and function. Strikingly, patients in each clinic sample and overall showed a wide distribution in all scores and measures. Conclusions: Illness heterogeneity may be an inherent feature of ME/CFS. Presenting research data in scatter plots or histograms will help clarify the challenge. Relying on case–control study designs without subgrouping or stratification of ME/CFS illness characteristics may limit the reproducibility of research findings and could obscure underlying mechanisms. © 2024 by the authors. |
Exploring recent decreases in first molar sealants among US children
Lin M . J Dent Res 2024 220345241231774 Analyses of National Health and Nutrition Examination Survey (NHANES) data suggested a significant decrease in sealant prevalence among children between 2011 to 2014 and 2015 to 2018. We explore whether this decrease could be associated with possible changes in 1) clinical sealant delivery, 2) dental materials (i.e., increased use of glass ionomer [GI] sealants resulting in an inability to detect sealant fragments that still provide preventive benefits or increased use of composite restorations leading to misclassifying sealants as restorations), and 3) examination sensitivity and specificity. We used NHANES data to estimate the prevalences of sealants, untreated caries, and restorations in ≥1 first permanent molar among children aged 7 to 10 y and used Medical Expenditure Panel Survey data to estimate the annual clinical delivery of sealants and fluoride treatments. We examined changes in outcomes between 2 periods (P < 0.05) controlling for selected sociodemographic characteristics. NHANES sealant examination quality was based on the reference examiner's replicate examinations. The adjusted prevalence of sealants decreased relatively by 27.5% (46.6% vs. 33.8%). Overall, untreated caries decreased. Untreated caries and restoration decreased among children without sealants. Annual clinical sealant delivery did not change, whereas fluoride treatment delivery increased. The decrease in sealant prevalence held when assessed for various age ranges and NHANES cycle combinations. While sealant examination specificity remained similar between the periods, sensitivity (weighted by the proportion of exams by each examiner) decreased relatively by 17.4% (0.92 vs. 0.76). These findings suggest that decreased sealant prevalence was not supported by decreased clinical sealant delivery nor increased use of composite restorations. Decreased examination sensitivity, which could be due to an increased use of GI sealants, could contribute to the decrease in sealant prevalence. The decrease in caries among children without sealants could suggest the increased use of GI sealants. However, we could not rule out that the decrease in caries could be attributable to increased fluoride treatment delivery. |
Infectious diseases among people experiencing homelessness: A systematic review of the literature in the United States and Canada, 2003-2022
Waddell CJ , Saldana CS , Schoonveld MM , Meehan AA , Lin CK , Butler JC , Mosites E . Public Health Rep 2024 333549241228525 Homelessness increases the risk of acquiring an infectious disease. We conducted a systematic review of the literature to identify quantitative data related to infectious diseases and homelessness. We searched Google Scholar, PubMed, and SCOPUS for quantitative literature published from January 2003 through December 2022 in English from the United States and Canada. We excluded literature on vaccine-preventable diseases and HIV because these diseases were recently reviewed. Of the 250 articles that met inclusion criteria, more than half were on hepatitis C virus or Mycobacterium tuberculosis. Other articles were on COVID-19, respiratory syncytial virus, Staphylococcus aureus, group A Streptococcus, mpox (formerly monkeypox), 5 sexually transmitted infections, and gastrointestinal or vectorborne pathogens. Most studies showed higher prevalence, incidence, or measures of risk for infectious diseases among people experiencing homelessness as compared with people who are housed or the general population. Although having increased published data that quantify the infectious disease risks of homelessness is encouraging, many pathogens that are known to affect people globally who are not housed have not been evaluated in the United States or Canada. Future studies should focus on additional pathogens and factors leading to a disproportionately high incidence and prevalence of infectious diseases among people experiencing homelessness. |
Subtyping Cryptosporidium ubiquitum,a zoonotic pathogen emerging in humans.
Li N , Xiao L , Alderisio K , Elwin K , Cebelinski E , Chalmers R , Santin M , Fayer R , Kvac M , Ryan U , Sak B , Stanko M , Guo Y , Wang L , Zhang L , Cai J , Roellig D , Feng Y . Emerg Infect Dis 2014 20 (2) 217-24 Cryptosporidium ubiquitum is an emerging zoonotic pathogen. In the past, it was not possible to identify an association between cases of human and animal infection. We conducted a genomic survey of the species, developed a subtyping tool targeting the 60-kDa glycoprotein (gp60) gene, and identified 6 subtype families (XIIa-XIIf) of C. ubiquitum. Host adaptation was apparent at the gp60 locus; subtype XIIa was found in ruminants worldwide, subtype families XIIb-XIId were found in rodents in the United States, and XIIe and XIIf were found in rodents in the Slovak Republic. Humans in the United States were infected with isolates of subtypes XIIb-XIId, whereas those in other areas were infected primarily with subtype XIIa isolates. In addition, subtype families XIIb and XIId were detected in drinking source water in the United States. Contact with C. ubiquitum-infected sheep and drinking water contaminated by infected wildlife could be sources of human infections. |
Evaluation of viral heterogeneity using next-generation sequencing, end-point limiting-dilution and mass spectrometry.
Dimitrova Z , Campo DS , Ramachandran S , Vaughan G , Ganova-Raeva L , Lin Y , Forbi JC , Xia G , Skums P , Pearlman B , Khudyakov Y . In Silico Biol 2011 11 183-92 Hepatitis C Virus sequence studies mainly focus on the viral amplicon containing the Hypervariable region 1 (HVR1) to obtain a sample of sequences from which several population genetics parameters can be calculated. Recent advances in sequencing methods allow for analyzing an unprecedented number of viral variants from infected patients and present a novel opportunity for understanding viral evolution, drug resistance and immune escape. In the present paper, we compared three recent technologies for amplicon analysis: (i) Next-Generation Sequencing; (ii) Clonal sequencing using End-point Limiting-dilution for isolation of individual sequence variants followed by Real-Time PCR and sequencing; and (iii) Mass spectrometry of base-specific cleavage reactions of a target sequence. These three technologies were used to assess intra-host diversity and inter-host genetic relatedness in HVR1 amplicons obtained from 38 patients (subgenotypes 1a and 1b). Assessments of intra-host diversity varied greatly between sequence-based and mass-spectrometry-based data. However, assessments of inter-host variability by all three technologies were equally accurate in identification of genetic relatedness among viral strains. These results support the application of all three technologies for molecular epidemiology and population genetics studies. Mass spectrometry is especially promising given its high throughput, low cost and comparable results with sequence-based methods. |
Some patients with type 2 diabetes may benefit from intensive glycaemic and blood pressure control: A post-hoc machine learning analysis of ACCORD trial data
Jiao T , Kianmehr H , Lin Y , Li P , Singh Ospina N , Ghayee HK , Ruzieh M , Fonseca V , Shi L , Zhang P , Shao H . Diabetes Obes Metab 2024 AIM: The action to control cardiovascular risk in diabetes (ACCORD) trial showed a neutral average treatment effect of intensive blood glucose and blood pressure (BP) controls in preventing major adverse cardiovascular events (MACE) in individuals with type 2 diabetes. Yet, treatment effects across patient subgroups have not been well understood. We aimed to identify patient subgroups that might benefit from intensive glucose or BP controls for preventing MACE. MATERIALS AND METHODS: As a post-hoc analysis of the ACCORD trial, we included 10 251 individuals with type 2 diabetes. We applied causal forest and causal tree models to identify participant characteristics that modify the efficacy of intensive glucose or BP controls from 68 candidate variables (demographics, comorbidities, medications and biomarkers) at the baseline. The exposure was (a) intensive versus standard glucose control [glycated haemoglobin (HbA1c) <6.0% vs. 7.0%-7.9%], and (b) intensive versus standard BP control (systolic BP <120 vs. <140 mmHg). The primary outcome was MACE. RESULTS: Compared with standard glucose control, intensive one reduced MACE in those with baseline HbA1c <8.5% [relative risk (RR): 0.79, 95% confidence interval (CI): 0.67-0.93] and those with estimated glomerular filtration rate ≥106 ml/min/1.73 m(2) (RR: 0.74, 95% CI: 0.55-0.99). Intensive BP control reduced MACE in those with normal high-density lipoprotein levels (women >55 mg/dl, men >45 mg/dl; RR: 0.51, 95% CI: 0.34-0.74). Risk reductions were not significant in other patient subgroups. CONCLUSIONS: Our findings suggest heterogeneous treatment effects of intensive glucose and BP control and could provide biomarkers for future clinical trials to identify more precise HbA1c and BP treatment goals for individualized medicine. |
One Health assessment of persistent organic chemicals and PFAS for consumption of restored anadromous fish
Melnyk LJ , Lazorchak JM , Kusnierz DH , Perlman GD , Lin J , Venkatapathy R , Sundaravadivelu D , Thorn J , Durant J , Pugh K , Stover MA . J Expo Sci Environ Epidemiol 2023 BACKGROUND: Restoration efforts have led to the return of anadromous fish, potential source of food for the Penobscot Indian Nation, to the previously dammed Penobscot River, Maine. OBJECTIVE: U.S. Environmental Protection Agency (EPA), Penobscot Indian Nation's Department of Natural Resources (PINDNR), and Agency for Toxic Substances and Disease Registry (ATSDR), measured contaminants in six species of anadromous fish. Fish tissue concentrations were then used, along with exposure parameters, to evaluate potential human and aquatic-dependent wildlife risk. METHODS: PINDNR collected, filleted, froze, and shipped fish for analysis of polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), dioxins/furans, and per- and polyfluoroalkyl substances (PFAS). Contaminant levels were compared to reference doses (where possible) and wildlife values (WVs). RESULTS: Chemical concentrations ranged from 6.37 nanogram per gram (ng/g) wet weight (ww) in American Shad roe to 100 ng/g ww in Striped Bass for total PCBs; 0.851 ng/g ww in American Shad roe to 5.92 ng/g ww in large Rainbow Smelt for total PBDEs; and 0.037 ng/g ww in American Shad roe to 0.221 ng/g ww in Striped Bass for total dioxin/furans. PFAS concentrations ranged between 0.38 ng/g ww of PFBA in Alewife to 7.86 ng/g ww of PFUnA in Sea Lamprey. Dioxin/furans and PFOS levels indicated that there are potential human health risks. The WV for mink for total PCBs (72 ng/g) was exceeded in Striped Bass and the WV for Kestrel for PBDEs (8.7 ng/g) was exceeded in large Rainbow Smelt. Mammalian wildlife consuming Blueback Herring, Striped Bass, and Sea Lamprey may be at risk based on PFOS WVs from Canada. IMPACT: Anadromous fish returning to the Penobscot River potentially could represent the restoration of a major component of tribal traditional diet. However, information about contaminant levels in these fish is needed to guide the tribe about consumption safety. Analysis of select species of fish and risk calculations demonstrated the need for a protective approach to consumption for both humans and wildlife. This project demonstrates that wildlife can also be impacted by contamination of fish and their risks can be as great or greater than those of humans. A One Health approach addresses this discrepancy and will lead to a healthier ecosystem. |
4,4'-Methylene diphenyl diisocyanate exposure induces expression of alternatively activated macrophage-associated markers and chemokines partially through Krüppel-like factor 4 mediated signaling in macrophages
Lin CC , Law BF , Hettick JM . Xenobiotica 2023 53 (12) 1-17 Occupational exposure to the most widely used monomeric diisocyanate (dNCO), 4,4'-methylene diphenyl diisocyanate (MDI), may lead to the development of occupational asthma (OA). Alveolar macrophages with alternatively activated (M2) phenotype have been implicated in allergic airway responses and the pathogenesis of asthma. Recent in vivo studies demonstrate that M2 macrophage-associated markers and chemokines are induced by MDI-exposure, however, the underlying molecular mechanism(s) by which this proceeds is unclear.Following MDI exposure (in vivo and in vitro) M2 macrophage-associated transcription factors (TFs), markers, and chemokines were determined by RT-qPCR, western blots, and ELISA.Expression of M2 macrophage-associated TFs and markers including Klf4/KLF4, Cd206/CD206, Tgm2/TGM2, Ccl17/CCL17, Ccl22/CCL22, and CCL24 were induced by MDI/MDI-GSH exposure in bronchoalveolar lavage cells (BALCs)/THP-1 macrophages. The expression of CD206, TGM2, CCL17, CCL22, and CCL24 are upregulated by 3.83-, 7.69-, 6.22-, 6.08-, and 1.90-fold in KLF4-overexpressed macrophages, respectively. Endogenous CD206 and TGM2 were downregulated by 1.65-5.17-fold, and 1.15-1.78-fold, whereas CCL17, CCL22, and CCL24 remain unchanged in KLF4-knockdown macrophages. Finally, MDI-glutathione (GSH) conjugate-treated macrophages show increased chemotactic ability to T-cells and eosinophils, which may be attenuated by KLF4 knockdown.Our data suggest that MDI exposure may induce M2 macrophage-associated markers partially through induction of KLF4. |
Monoclonal antibodies as SARS-CoV-2 serology standards: Experimental validation and broader implications for correlates of protection
Wang L , Patrone PN , Kearsley AJ , Izac JR , Gaigalas AK , Prostko JC , Kwon HJ , Tang W , Kosikova M , Xie H , Tian L , Elsheikh EB , Kwee EJ , Kemp T , Jochum S , Thornburg N , McDonald LC , Gundlapalli AV , Lin-Gibson S . Int J Mol Sci 2023 24 (21) COVID-19 has highlighted challenges in the measurement quality and comparability of serological binding and neutralization assays. Due to many different assay formats and reagents, these measurements are known to be highly variable with large uncertainties. The development of the WHO international standard (WHO IS) and other pool standards have facilitated assay comparability through normalization to a common material but does not provide assay harmonization nor uncertainty quantification. In this paper, we present the results from an interlaboratory study that led to the development of (1) a novel hierarchy of data analyses based on the thermodynamics of antibody binding and (2) a modeling framework that quantifies the probability of neutralization potential for a given binding measurement. Importantly, we introduced a precise, mathematical definition of harmonization that separates the sources of quantitative uncertainties, some of which can be corrected to enable, for the first time, assay comparability. Both the theory and experimental data confirmed that mAbs and WHO IS performed identically as a primary standard for establishing traceability and bridging across different assay platforms. The metrological anchoring of complex serological binding and neuralization assays and fast turn-around production of an mAb reference control can enable the unprecedented comparability and traceability of serological binding assay results for new variants of SARS-CoV-2 and immune responses to other viruses. |
Intussusception risk following oral monovalent rotavirus vaccination in 3 Asian countries: A self-control case series evaluation
Burnett E , Riaz A , Anwari P , Myat TW , Chavers TP , Talat N , Safi N , Aung NNT , Cortese MM , Sultana S , Samsor A , Thu HM , Saddal NS , Safi S , Lin H , Qazi SH , Safi H , Ali A , Parashar UD , Tate JE . Vaccine 2023 41 (48) 7220-7225 Rotavirus vaccines have substantially decreased rotavirus hospitalizations in countries where they have been implemented. In some high- and middle-income countries, a low-level of increased risk of intussusception, a type of acute bowel obstruction, has been detected following rotavirus vaccination. However, no increased risk of intussusception was found in India, South Africa, or a network of 7 other African countries. We assessed the association between a 2-dose monovalent rotavirus vaccine (Rotarix) and intussusception in 3 early-adopter low-income Asian countries -- Afghanistan, Myanmar, and Pakistan. Children <12 months of age admitted to a sentinel surveillance hospital with Brighton level 1 intussusception were eligible for enrollment. We collected information about each child's vaccination status and used the self-controlled case series method to calculate the relative incidence of intussusception 1-7 days, 8-21 days, and 1-21 days following each dose of vaccine and derived confidence intervals with bootstrapping. Of the 585 children meeting the analytic criteria, the median age at intussusception symptom onset was 24 weeks (IQR: 19-29). Overall, 494 (84 %) children received the first Rotarix dose and 398 (68 %) received the second dose. There was no increased intussusception risk during any of the risk periods following the first (1-7 days: 1.01 (95 %CI: 0.39, 2.60); 8-21 days: 1.37 (95 %CI: 0.81, 2.32); 1-21 days: 1.28 (95 %CI: 0.78, 2.11)) or second (1-7 days: 0.81 (95 %CI: 0.42, 1.54); 8-21 days: 0.77 (95 %CI: 0.53, 1.16); 1-21 days: 0.78 (95 %CI: 0.53, 1.16)) rotavirus vaccine dose. Our findings are consistent with other data showing no increased intussusception risk with rotavirus vaccination in low-income countries and add to the growing body of evidence demonstrating safety of rotavirus vaccines. |
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. |
Risk factors for heat-related illness resulting in death or hospitalization in the oil and gas extraction industry
Lin NW , Ramirez-Cardenas A , Wingate KC , King BS , Scott K , Hagan-Hayes K . J Occup Environ Hyg 2023 1-14 Many oil and gas extraction (OGE) activities occur in high heat environments, resulting in significant risk of heat-related illness among outdoor workers in this industry. This report highlights cases of occupational heat-related illness that resulted in death and identifies common risk factors for heat-related fatalities and hospitalizations among OGE workers. Two databases maintained by the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA) were reviewed to identify heat-related fatalities, hospitalizations, and associated risk factors among OGE workers. Nine fatalities and associated risk factors were identified during 2014-2019 from NIOSH's Fatalities in Oil and Gas Extraction (FOG) Database. Risk factors identified included those commonly associated with heat-related fatalities: new workers not acclimatized to heat, inadequate heat stress training, and underlying hypertension or cardiovascular disease. Of particular note, substance use was identified as a significant risk factor as more than half of the fatalities included a positive post-mortem test for amphetamines or methamphetamines. Fifty heat-related hospitalizations were identified from OSHA's Severe Injury Report Database during January 2015-May 2021. Heat stress has been and will continue to be an important cause of fatality and adverse health effects in OGE as hot outdoor working conditions become more common and extreme. More emphasis on heat stress training, acclimatization regimens, medical screening, and implementation of workplace supportive recovery programs may reduce heat-related fatalities and injuries in this industry. |
Comparison of demographic characteristics and social determinants of health between adults with diagnosed HIV and all adults in the US
Dasgupta S , McManus T , Tie Y , Lin CY , Yuan X , Sharpe JD , Fletcher KM , Beer L . AJPM Focus 2023 2 (3) 100115 INTRODUCTION: Quantifying disparities in social determinants of health between people with HIV and the total population could help address health inequities, and ensure health and well-being among people with HIV in the U.S., but estimates are lacking. METHODS: Several representative data sources were used to assess differences in social determinants of health between adults with diagnosed HIV (Centers for Disease Control and Prevention Medical Monitoring Project) and the total adult population (U.S. Census Bureau's decennial census, American Community Survey, Household Pulse Survey, the Current Population Survey Annual Social and Economic Supplements; the Department of Housing and Urban Development's point-in-time estimates of homelessness; and the Bureau of Justice Statistics). The differences were quantified using standardized prevalence differences and standardized prevalence ratios, adjusting for differences in age, race/ethnicity, and birth sex between people with HIV and the total U.S. population. RESULTS: Overall, 35.6% of people with HIV were living in a household with an income at or below the federal poverty level, and 8.1% recently experienced homelessness. Additionally, 42.9% had Medicaid and 27.6% had Medicare; 39.7% were living with a disability. Over half (52.3%) lived in large central metropolitan counties and 20.6% spoke English less than very well based on survey responses. After adjustment, poverty (standardized prevalence difference=25.1%, standardized prevalence ratio=3.5), homelessness (standardized prevalence difference=8.5%, standardized prevalence ratio=43.5), coverage through Medicaid (standardized prevalence difference=29.5%, standardized prevalence ratio=3.0) or Medicare (standardized prevalence difference=7.8%), and disability (standardized prevalence difference=30.3%, standardized prevalence ratio=3.0) were higher among people with HIV than the total U.S. population. The percentage of people with HIV living in large central metropolitan counties (standardized prevalence difference=13.4%) or who were recently incarcerated (standardized prevalence ratio=5.9) was higher than the total U.S. population. CONCLUSIONS: These findings provide a baseline for assessing national-level disparities in social determinants of health between people with HIV and the total U.S. population, and it can be used as a model to assess local disparities. Addressing social determinants of health is essential for achieving health equity, requiring a multipronged approach with interventions at the provider, facility, and policy levels. |
A technology-enabled multi-disciplinary team-based care model for the management of Long COVID and other fatiguing illnesses within a federally qualified health center: protocol for a two-arm, single-blind, pragmatic, quality improvement professional cluster randomized controlled trial
Godino JG , Samaniego JC , Sharp SP , Taren D , Zuber A , Armistad AJ , Dezan AM , Leyba AJ , Friedly JL , Bunnell AE , Matthews E , Miller MJ , Unger ER , Bertolli J , Hinckley A , Lin JS , Scott JD , Struminger BB , Ramers C . Trials 2023 24 (1) 524 BACKGROUND: The clinical burden of Long COVID, myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), and other post-infectious fatiguing illnesses (PIFI) is increasing. There is a critical need to advance understanding of the effectiveness and sustainability of innovative approaches to clinical care of patients having these conditions. METHODS: We aim to assess the effectiveness of a Long COVID and Fatiguing Illness Recovery Program (LC&FIRP) in a two-arm, single-blind, pragmatic, quality improvement, professional cluster, randomized controlled trial in which 20 consenting clinicians across primary care clinics in a Federally Qualified Health Center system in San Diego, CA, will be randomized at a ratio of 1:1 to either participate in (1) weekly multi-disciplinary team-based case consultation and peer-to-peer sharing of emerging best practices (i.e., teleECHO (Extension for Community Healthcare Outcomes)) with monthly interactive webinars and quarterly short courses or (2) monthly interactive webinars and quarterly short courses alone (a control group); 856 patients will be assigned to participating clinicians (42 patients per clinician). Patient outcomes will be evaluated according to the study arm of their respective clinicians. Quantitative and qualitative outcomes will be measured at 3- and 6-months post-baseline for clinicians and every 3-months post assignment to a participating clinician for patients. The primary patient outcome is change in physical function measured using the Patient-Reported Outcomes Measurement Information System (PROMIS)-29. Analyses of differences in outcomes at both the patient and clinician levels will include a linear mixed model to compare change in outcomes from baseline to each post-baseline assessment between the randomized study arms. A concurrent prospective cohort study will compare the LC&FIRP patient population to the population enrolled in a university health system. Longitudinal data analysis approaches will allow us to examine differences in outcomes between cohorts. DISCUSSION: We hypothesize that weekly teleECHO sessions with monthly interactive webinars and quarterly short courses will significantly improve clinician- and patient-level outcomes compared to the control group. This study will provide much needed evidence on the effectiveness of a technology-enabled multi-disciplinary team-based care model for the management of Long COVID, ME/CFS, and other PIFI within a federally qualified health center. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05167227 . Registered on December 22, 2021. |
Addressing Personal Protective Equipment (PPE) Decontamination: Methylene Blue and Light Inactivates SARS-CoV-2 on N95 Respirators and Masks with Maintenance of Integrity and Fit (preprint)
Lendvay TS , Chen J , Harcourt BH , Scholte FE , Lin YL , Kilinc-Balci FS , Lamb MM , Homdayjanakul K , Cui Y , Price A , Heyne B , Sahni J , Kabra KB , Lin YC , Evans D , Mores CN , Page K , Chu LF , Haubruge E , Thiry E , Ludwig-Begall LF , Wielick C , Clark T , Wagner T , Timm E , Gallagher T , Faris P , Macia N , Mackie CJ , Simmons SM , Reader S , Malott R , Hope K , Davies JM , Tritsch SR , Dams L , Nauwynck H , Willaert JF , De Jaeger S , Liao L , Zhao M , Laperre J , Jolois O , Smit SJ , Patel AN , Mayo M , Parker R , Molloy-Simard V , Lemyre JL , Chu S , Conly JM , Chu MC . medRxiv 2020 2020.12.11.20236919 Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in severe shortages of personal protective equipment (PPE) necessary to protect front-line healthcare personnel. These shortages underscore the urgent need for simple, efficient, and inexpensive methods to decontaminate SARS-CoV-2-exposed PPE enabling safe reuse of masks and respirators. Efficient decontamination must be available not only in low-resourced settings, but also in well-resourced settings affected by PPE shortages. Methylene blue (MB) photochemical treatment, hitherto with many clinical applications including those used to inactivate virus in plasma, presents a novel approach for widely applicable PPE decontamination. Dry heat (DH) treatment is another potential low-cost decontamination method.Methods MB and light (MBL) and DH treatments were used to inactivate coronavirus on respirator and mask material. We tested three N95 filtering facepiece respirators (FFRs), two medical masks (MMs), and one cloth community mask (CM). FFR/MM/CM materials were inoculated with SARS-CoV-2 (a Betacoronavirus), murine hepatitis virus (MHV) (a Betacoronavirus), or porcine respiratory coronavirus (PRCV) (an Alphacoronavirus), and treated with 10 µM MB followed by 50,000 lux of broad-spectrum light or 12,500 lux of red light for 30 minutes, or with 75°C DH for 60 minutes. In parallel, we tested respirator and mask integrity using several standard methods and compared to the FDA-authorized vaporized hydrogen peroxide plus ozone (VHP+O3) decontamination method. Intact FFRs/MMs/CM were subjected to five cycles of decontamination (5CD) to assess integrity using International Standardization Organization (ISO), American Society for Testing and Materials (ASTM) International, National Institute for Occupational Safety and Health (NIOSH), and Occupational Safety and Health Administration (OSHA) test methods.Findings Overall, MBL robustly and consistently inactivated all three coronaviruses with at least a 4-log reduction. DH yielded similar results, with the exception of MHV, which was only reduced by 2-log after treatment. FFR/MM integrity was maintained for 5 cycles of MBL or DH treatment, whereas one FFR failed after 5 cycles of VHP+O3. Baseline performance for the CM was variable, but reduction of integrity was minimal.Interpretation Methylene blue with light and DH treatment decontaminated masks and respirators by inactivating three tested coronaviruses without compromising integrity through 5CD. MBL decontamination of masks is effective, low-cost and does not require specialized equipment, making it applicable in all-resource settings. These attractive features support the utilization and continued development of this novel PPE decontamination method.Competing Interest StatementAuthors Thomas S. Lendvay, James Chen are Co-Founders and equity owners of Singletto, Inc. (Seattle, WA, USA) Authors Yi Cui and Steven Chu are Co-Founders and equity owners of 4C Air, Inc. (Sunnyvale, CA)Funding StatementThis study was funded by Open Philanthropy; Amazon Inc./University of Washington Catalyst Award; University of Liege (Belgium) and the Walloon Region, Belgium; Li Ka Shing Institute; Alberta Health Services; and an Anonymous donor to the University of Washington, Department of Urology.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:Stanford University and Alberta Health Services/University of Calgary were exempt from IRB as the human fit testing was considered Quality Improvement. ERB for clinical specimen use: A clinical saliva specimen with a SARS-CoV-2 was provided by Dr. John Conly from Calgary, Alberta with Calgary ERB approval (ID# Pro00099761).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 inte ventional 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 will be freely shared post publication on reasonable request by contacting the corresponding author of the study. |
The distribution and spread of susceptible and resistant Neisseria gonorrhoeae across demographic groups in a major metropolitan center (preprint)
Mortimer TD , Pathela P , Crawley A , Rakeman JL , Lin Y , Harris SR , Blank S , Schillinger JA , Grad YH . medRxiv 2020 2020.04.30.20086413 Background Genomic epidemiology studies of gonorrhea in the United States have primarily focused on national surveillance for antibiotic resistance, and patterns of local transmission between demographic groups of resistant and susceptible strains are unknown.Methods We analyzed a convenience sample of genome sequences, antibiotic susceptibility, and patient data from 897 gonococcal isolates cultured at the NYC Public Health Laboratory from NYC Department of Health and Mental Hygiene (DOHMH) Sexual Health Clinic (SHC) patients, primarily in 2012-13. We reconstructed the gonococcal phylogeny, defined transmission clusters using a 10 non-recombinant single nucleotide polymorphism threshold, tested for clustering of demographic groups, and placed NYC isolates in a global phylogenetic context.Results The NYC gonococcal phylogeny reflected global diversity with isolates from 22/23 of the prevalent global lineages (96%). Isolates clustered on the phylogeny by patient sexual behavior (p<0.001) and race/ethnicity (p<0.001).Minimum inhibitory concentrations were higher across antibiotics in isolates from men who have sex with men compared to heterosexuals (p<0.001) and white heterosexuals compared to black heterosexuals (p<0.01). In our dataset, all large transmission clusters (≥10 samples) of N. gonorrhoeae were susceptible to ciprofloxacin, ceftriaxone, and azithromycin and comprised isolates from patients across demographic groups.Conclusions All large transmission clusters were susceptible to gonorrhea therapies, suggesting that resistance to empiric therapy was not a main driver of spread, even as risk for resistance varied across demographic groups. Further study of local transmission networks is needed to identify drivers of transmission.Competing Interest StatementThe authors have declared no competing interest.Funding StatementThis work was supported by the National Institute of Allergy and Infectious Diseases at the National Institutes of Health [R01 AI132606 and 1 F32 AI145157-01] and the Wellcome Trust [098051].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.YesWhole genome sequencing data were deposited in the European Nucleotide Archive (ERA) under study accession PRJEB10016. All additional data and scripts are available at https://github.com/gradlab/GC_NYC. https://www.ebi.ac.uk/ena/data/view/PRJEB10016 https://github.com/gradlab/GC_NYC |
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. |
COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support (preprint)
Shea K , Borchering RK , Probert WJM , Howerton E , Bogich TL , Li S , van Panhuis WG , Viboud C , Aguás R , Belov A , Bhargava SH , Cavany S , Chang JC , Chen C , Chen J , Chen S , Chen Y , Childs LM , Chow CC , Crooker I , Valle SYD , España G , Fairchild G , Gerkin RC , Germann TC , Gu Q , Guan X , Guo L , Hart GR , Hladish TJ , Hupert N , Janies D , Kerr CC , Klein DJ , Klein E , Lin G , Manore C , Meyers LA , Mittler J , Mu K , Núñez RC , Oidtman R , Pasco R , Piontti APY , Paul R , Pearson CAB , Perdomo DR , Perkins TA , Pierce K , Pillai AN , Rael RC , Rosenfeld K , Ross CW , Spencer JA , Stoltzfus AB , Toh KB , Vattikuti S , Vespignani A , Wang L , White L , Xu P , Yang Y , Yogurtcu ON , Zhang W , Zhao Y , Zou D , Ferrari M , Pannell D , Tildesley M , Seifarth J , Johnson E , Biggerstaff M , Johansson M , Slayton RB , Levander J , Stazer J , Salerno J , Runge MC . medRxiv 2020 Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes. |
A Pan-respiratory Antiviral Chemotype Targeting a Transient Host Multiprotein Complex (preprint)
Muller-Schiffmann A , Michon M , Lingappa AF , Yu SF , Du L , Deiter F , Broce S , Mallesh S , Crabtree J , Lingappa UF , Macieik A , Muller L , Ostermann PN , Andree M , Adams O , Schaal H , Hogan RJ , Tripp RA , Appaiah U , Anand SK , Campi TW , Ford MJ , Reed JC , Lin J , Akintunde O , Copeland K , Nichols C , Petrouski E , Moreira AR , Jiang IT , DeYarman N , Brown I , Lau S , Segal I , Goldsmith D , Hong S , Asundi V , Briggs EM , Phyo NS , Froehlich M , Onisko B , Matlack K , Dey D , Lingappa JR , Prasad MD , Kitaygorodskyy A , Solas D , Boushey H , Greenland J , Pillai S , Lo MK , Montgomery JM , Spiropoulou CF , Korth C , Selvarajah S , Paulvannan K , Lingappa VR . bioRxiv 2021 18 We present a small molecule chemotype, identified by an orthogonal drug screen, exhibiting nanomolar activity against members of all the six viral families causing most human respiratory viral disease, with a demonstrated barrier to resistance development. Antiviral activity is shown in mammalian cells, including human primary bronchial epithelial cells cultured to an air-liquid interface and infected with SARS-CoV-2. In animals, efficacy of early compounds in the lead series is shown by survival (for a coronavirus) and viral load (for a paramyxovirus). The drug target is shown to include a subset of the protein 14-3-3 within a transient host multi-protein complex containing components implicated in viral lifecycles and in innate immunity. This multi-protein complex is modified upon viral infection and largely restored by drug treatment. Our findings suggest a new clinical therapeutic strategy for early treatment upon upper respiratory viral infection to prevent progression to lower respiratory tract or systemic disease. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. |
Changes in Transmission and Symptoms of SARS-CoV-2 in United States Households, April 2020-September 2022 (preprint)
Mellis AM , Lauring AS , Talbot HK , McLean HQ , Morrissey KG , Stockwell MS , Bowman NM , Maldonado Y , Ellingson KD , Rao S , Biddle JE , Johnson S , Ogokeh C , Salvatore PP , Reed C , Smith-Jeffcoat SE , Meece JK , Hanson KE , Belongia EA , Bendall EE , Gilbert J , Olivo V , Merrill LS , McLaren SH , Sano E , Vargas CY , Saiman L , Silverio Francisco RA , Bullock A , Lin J , Govindarajan P , Goodman SH , Sarnquist CC , Lutrick K , Ledezma KI , Ramadan FA , Pryor K , Miiro FN , Asturias E , Dominguez S , Olson D , Izurieta HS , Chappell J , Lindsell C , Halasa N , Hart K , Zhu Y , Schmitz J , Rolfes MA , Grijalva CG . medRxiv 2023 19 Background: The natural history of SARS-CoV-2 infection and transmission dynamics may have changed as SARS-CoV-2 has evolved and population immunity has shifted. Method(s): Household contacts, enrolled from two multi-site case-ascertained household transmission studies (April 2020-April 2021 and September 2021-September 2022), were followed for 10-14 days after enrollment with daily collection of nasal swabs and/or saliva for SARS-CoV-2 testing and symptom diaries. SARS-CoV-2 virus lineage was determined by whole genome sequencing, with multiple imputation where sequences could not be recovered. Adjusted infection risks were estimated using modified Poisson regression. Finding(s): 858 primary cases with 1473 household contacts were examined. Among unvaccinated household contacts, the infection risk adjusted for presence of prior infection and age was 58% (95% confidence interval [CI]: 49-68%) in households currently exposed to pre-Delta lineages and 90% (95% CI: 74-100%) among those exposed to Omicron BA.5 (detected May - September 2022). The fraction of infected household contacts reporting any symptom was similarly high between pre-Delta (86%, 95% CI: 81-91%) and Omicron lineages (77%, 70-85%). Among Omicron BA.5-infected contacts, 48% (41-56%) reported fever, 63% (56-71%) cough, 22% (17-28%) shortness of breath, and 20% (15-27%) loss of/change in taste/smell. Interpretation(s): The risk of infection among household contacts exposed to SARS-CoV-2 is high and increasing with more recent SARS-CoV-2 lineages. This high infection risk highlights the importance of vaccination to prevent severe disease. Funding(s): Funded by the Centers for Disease Control and Prevention and the Food and Drug Administration. 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. |
Non-falciparum malaria infections are as prevalent as P. falciparum among Tanzanian schoolchildren (preprint)
Sendor R , Mitchell CL , Chacky F , Mohamed A , Mhamilawa LE , Molteni F , Nyinondi S , Kabula B , Mkali H , Reaves EJ , Serbantez N , Kitojo C , Makene T , Kyaw T , Muller M , Mwanza A , Eckert EL , Parr JB , Lin JT , Juliano JJ , Ngasala B . medRxiv 2022 08 Efforts to achieve malaria elimination need to consider both falciparum and nonfalciparum infections. The prevalence and geographic distribution of four Plasmodium species were determined by real-time PCR using dried blood spots collected during the 2017 School Malaria Parasitological Survey of eight regions of Tanzania. Among 3,456 schoolchildren, 22% had P. falciparum, 24% P. ovale spp., 4% P. malariae, and 0.3% P. vivax. Ninety-one percent of P. ovale infections had very low parasite densities, based on amplification at later cycle thresholds. Sixty-four percent of P. ovale infections were single-species, and 35% of these were detected in low malaria endemicity regions. P. malariae infections were predominantly co-infections with P. falciparum (73%). P. vivax was largely detected in northern and eastern regions. Overall, 43% of children with P. falciparum were co-infected with at least one nonfalciparum species. A large, previously under-appreciated burden of P. ovale spp. infection exists among Tanzanian schoolchildren. Copyright The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission. |
Bivalent mRNA vaccine improves antibody-mediated neutralization of many SARS-CoV-2 Omicron lineage variants (preprint)
Jiang N , Wang L , Hatta M , Feng C , Currier M , Lin X , Hossain J , Cui D , Mann BR , Kovacs NA , Wang W , Atteberry G , Wilson M , Chau R , Lacek KA , Paden CR , Hassell N , Rambo-Martin B , Barnes JR , Kondor RJ , Self WH , Rhoads JP , Baughman A , Chappell JD , Shapiro NI , Gibbs KW , Hager DN , Lauring AS , Surie D , McMorrow ML , Thornburg NJ , Wentworth DE , Zhou B . bioRxiv 2023 09 The early Omicron lineage variants evolved and gave rise to diverging lineages that fueled the COVID-19 pandemic in 2022. Bivalent mRNA vaccines, designed to broaden protection against circulating and future variants, were authorized by the U.S. Food and Drug Administration (FDA) in August 2022 and recommended by the U.S. Centers for Disease Control and Prevention (CDC) in September 2022. The impact of bivalent vaccination on eliciting neutralizing antibodies against homologous BA.4/BA.5 viruses as well as emerging heterologous viruses needs to be analyzed. In this study, we analyze the neutralizing activity of sera collected after a third dose of vaccination (2-6 weeks post monovalent booster) or a fourth dose of vaccination (2-7 weeks post bivalent booster) against 10 predominant/recent Omicron lineage viruses including BA.1, BA.2, BA.5, BA.2.75, BA.2.75.2, BN.1, BQ.1, BQ.1.1, XBB, and XBB.1. The bivalent booster vaccination enhanced neutralizing antibody titers against all Omicron lineage viruses tested, including a 10-fold increase in neutralization of BQ.1 and BQ.1.1 viruses that predominated in the U.S. during the last two months of 2022. Overall, the data indicate the bivalent vaccine booster strengthens protection against Omicron lineage variants that evolved from BA.5 and BA.2 progenitors. Copyright The copyright holder for this preprint is the author/funder, who has granted bioRxiv 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. |
Differential neutralization and inhibition of SARS-CoV-2 variants by antibodies elicited by COVID-19 mRNA vaccines (preprint)
Wang L , Kainulainen MH , Jiang N , Di H , Bonenfant G , Mills L , Currier M , Shrivastava-Ranjan P , Calderon BM , Sheth M , Hossain J , Lin X , Lester S , Pusch E , Jones J , Cui D , Chatterjee P , Jenks HM , Morantz E , Larson G , Hatta M , Harcourt J , Tamin A , Li Y , Tao Y , Zhao K , Burroughs A , Wong T , Tong S , Barnes JR , Tenforde MW , Self WH , Shapiro NI , Exline MC , Files DC , Gibbs KW , Hager DN , Patel M , Laufer Halpin AS , Lee JS , Xie X , Shi PY , Davis CT , Spiropoulou CF , Thornburg NJ , Oberste MS , Dugan V , Wentworth DE , Zhou B , Batra D , Beck A , Caravas J , Cintron-Moret R , Cook PW , Gerhart J , Gulvik C , Hassell N , Howard D , Knipe K , Kondor RJ , Kovacs N , Lacek K , Mann BR , McMullan LK , Moser K , Paden CR , Martin BR , Schmerer M , Shepard S , Stanton R , Stark T , Sula E , Tymeckia K , Unoarumhi Y . bioRxiv 2021 30 The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted in the emergence of many new variant lineages that have exacerbated the COVID-19 pandemic. Some of those variants were designated as variants of concern/interest (VOC/VOI) by national or international authorities based on many factors including their potential impact on vaccines. To ascertain and rank the risk of VOCs and VOIs, we analyzed their ability to escape from vaccine-induced antibodies. The variants showed differential reductions in neutralization and replication titers by post-vaccination sera. Although the Omicron variant showed the most escape from neutralization, sera collected after a third dose of vaccine (booster sera) retained moderate neutralizing activity against that variant. Therefore, vaccination remains the most effective strategy to combat the COVID-19 pandemic. |
Constructing state and national estimates of vaccination rates from immunization information systems
Raghunathan T , Kirtland K , Li J , White K , Murthy B , Lin XM , Harris L , Gibbs-Scharf L , Zell E . J Surv Stat Methodol 2023 11 (3) 688-712 Immunization Information Systems are confidential computerized population-based systems that collect data from vaccination providers on individual vaccinations administered along with limited patient-level characteristics. Through a data use agreement, Centers for Disease Control and Prevention obtains the individual-level data and aggregates the number of vaccinations for geographical statistical areas defined by the US Census Bureau (counties or equivalent statistical entities) for each vaccine included in system. Currently, 599 counties, covering 11 states, collect and report data using a uniform protocol. We combine these data with inter-decennial population counts from the Population Estimates Program in the US Census Bureau and several covariates from a variety of sources to develop model-based estimates for each of the 3,142 counties in 50 states and the District of Columbia and then aggregate to the state and national levels. We use a hierarchical Bayesian model and Markov Chain Monte Carlo methods to obtain draws from the posterior predictive distribution of the vaccination rates. We use posterior predictive checks and cross-validation to assess the goodness of fit and to validate the models. We also compare the model-based estimates to direct estimates from the National Immunization Surveys. © 2023 The Author(s). Published by Oxford University Press on behalf of the American Association for Public Opinion Research. All rights reserved. |
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