Last data update: Dec 02, 2024. (Total: 48272 publications since 2009)
Records 1-24 (of 24 Records) |
Query Trace: Whittaker B[original query] |
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Antigenic drift and subtype interference shape A(H3N2) epidemic dynamics in the United States
Perofsky AC , Huddleston J , Hansen CL , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Lewis N , Whittaker L , Ermetal B , Harvey R , Galiano M , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Sullivan SG , Barr IG , Subbarao K , Krammer F , Bedford T , Viboud C . Elife 2024 13 Influenza viruses continually evolve new antigenic variants, through mutations in epitopes of their major surface proteins, hemagglutinin (HA) and neuraminidase (NA). Antigenic drift potentiates the reinfection of previously infected individuals, but the contribution of this process to variability in annual epidemics is not well understood. Here, we link influenza A(H3N2) virus evolution to regional epidemic dynamics in the United States during 1997-2019. We integrate phenotypic measures of HA antigenic drift and sequence-based measures of HA and NA fitness to infer antigenic and genetic distances between viruses circulating in successive seasons. We estimate the magnitude, severity, timing, transmission rate, age-specific patterns, and subtype dominance of each regional outbreak and find that genetic distance based on broad sets of epitope sites is the strongest evolutionary predictor of A(H3N2) virus epidemiology. Increased HA and NA epitope distance between seasons correlates with larger, more intense epidemics, higher transmission, greater A(H3N2) subtype dominance, and a greater proportion of cases in adults relative to children, consistent with increased population susceptibility. Based on random forest models, A(H1N1) incidence impacts A(H3N2) epidemics to a greater extent than viral evolution, suggesting that subtype interference is a major driver of influenza A virus infection ynamics, presumably via heterosubtypic cross-immunity. | Seasonal influenza (flu) viruses cause outbreaks every winter. People infected with influenza typically develop mild respiratory symptoms. But flu infections can cause serious illness in young children, older adults and people with chronic medical conditions. Infected or vaccinated individuals develop some immunity, but the viruses evolve quickly to evade these defenses in a process called antigenic drift. As the viruses change, they can re-infect previously immune people. Scientists update the flu vaccine yearly to keep up with this antigenic drift. The immune system fights flu infections by recognizing two proteins, known as antigens, on the virus’s surface, called hemagglutinin (HA) and neuraminidase (NA). However, mutations in the genes encoding these proteins can make them unrecognizable, letting the virus slip past the immune system. Scientists would like to know how these changes affect the size, severity and timing of annual influenza outbreaks. Perofsky et al. show that tracking genetic changes in HA and NA may help improve flu season predictions. The experiments compared the severity of 22 flu seasons caused by the A(H3N2) subtype in the United States with how much HA and NA had evolved since the previous year. The A(H3N2) subtype experiences the fastest rates of antigenic drift and causes more cases and deaths than other seasonal flu viruses. Genetic changes in HA and NA were a better predictor of A(H3N2) outbreak severity than the blood tests for protective antibodies that epidemiologists traditionally use to track flu evolution. However, the prevalence of another subtype of influenza A circulating in the population, called A(H1N1), was an even better predictor of how severe A(H3N2) outbreaks would be. Perofsky et al. are the first to show that genetic changes in NA contribute to the severity of flu seasons. Previous studies suggested a link between genetic changes in HA and flu season severity, and flu vaccines include the HA protein to help the body recognize new influenza strains. The results suggest that adding the NA protein to flu vaccines may improve their effectiveness. In the future, flu forecasters may want to analyze genetic changes in both NA and HA to make their outbreak predictions. Tracking how much of the A(H1N1) subtype is circulating may also be useful for predicting the severity of A(H3N2) outbreaks. | eng |
Visualizing the NIOSH Pocket Guide: open-source web application for accessing and exploring the NIOSH Pocket Guide to Chemical Hazards
Lucas L , Whittaker C , Bailer AJ . J Occup Environ Hyg 2023 1-11 The NIOSH Pocket Guide to Chemical Hazards is a trusted resource that displays key information for a collection of chemicals commonly encountered in the workplace. Entries contain chemical structures, occupational exposure limit information ranging from limits based on full-shift time-weighted averages to acute limits such as short-term exposure limits and immediately dangerous to life or health values, as well as a variety of other data such as chemical-physical properties and symptoms of exposure. The NIOSH Pocket Guide (NPG) is available as a printed, hardcopy book, a PDF version, an electronic database, and a downloadable application for mobile phones. All formats of the NIOSH Pocket Guide allow users to access the data for each chemical separately, however, the guide does not support data analytics or visualization across chemicals. This project reformatted existing data in the NPG to make it searchable and compatible with exploration and analysis using a web application. The resulting application allows users to investigate the relationships between occupational exposure limits, the range and distribution of occupational exposure limits, and specialized sorting of chemicals by health endpoint or to summarize information of particular interest. These tasks would have previously required manual extraction of the data and analysis. The usability of this application was evaluated among industrial hygienists and researchers and while the existing application seems most relevant to researchers, the open-source code and data are amenable to modification by users to increase customization. |
Seasonal trends in emergency department visits for mental and behavioral health conditions among children and adolescents aged 5-17 years - United States, January 2018-June 2023
Radhakrishnan L , Carey K , Pell D , Ising A , Brathwaite D , Waller A , Gay J , Watson-Smith H , Person M , Zamore K , Brumsted T , Price C , Clark PM , Haas GA , Gracy L , Johnston S , Chen Y , Muñoz K , Henry M , Willis B , Nevels D , Asaolu I , Lee S , Wilkins NJ , Bacon S , Sheppard M , Kite-Powell A , Blau G , King M , Whittaker M , Leeb RT . MMWR Morb Mortal Wkly Rep 2023 72 (38) 1032-1040 Mental and behavioral health conditions among school-aged children, including substance use disorders and overall emotional well-being, are a public health concern in the United States. Timely data on seasonal patterns in child and adolescent conditions can guide optimal timing of prevention and intervention strategies. CDC examined emergency department (ED) visit data from the National Syndromic Surveillance Program for 25 distinct conditions during January 2018-June 2023 among U.S. children and adolescents aged 5-17 years, stratified by age group. Each year, during 2018-2023, among persons aged 10-14 and 15-17 years, the number and proportion of weekly ED visits for eight conditions increased in the fall school semester and remained elevated throughout the spring semester; ED visits were up to twice as high during school semesters compared with the summer period. Among children aged 5-9 years, the number and proportion of visits increased for five mental and behavioral health conditions. Seasonal increases in ED visits for some conditions among school-aged children warrant enhanced awareness about mental distress symptoms and the challenges and stressors in the school environment. Systemic changes that prioritize protective factors (e.g., physical activity; nutrition; sleep; social, community, or faith-based support; and inclusive school and community environments) and incorporate preparedness for increases in conditions during back-to-school planning might improve child and adolescent mental health. |
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution (preprint)
Huddleston J , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Whittaker L , Ermetal B , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Barr I , Subbarao K , Neher RA , Bedford T . bioRxiv 2020 2020.06.12.145151 Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence-only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth.Competing Interest StatementThe authors have declared no competing interest. |
Social Contact Patterns and Implications for Infectious Disease Transmission: A Systematic Review and Meta-Analysis of Contact Surveys (preprint)
Mousa A , Winskill P , Watson OJ , Ratmann O , Monod M , Ajelli M , Diallo A , Dodd PJ , Grijalva CG , Kiti MC , Krishnan A , Kumar R , Kumar S , Kwok KO , Lanata CF , Le Polain de Waroux O , Leung K , Mahikul W , Melegaro A , Morrow CD , Mossong J , Neal EF , Nokes DJ , Pan-Ngum W , Potter GE , Russell FM , Saha S , Sugimoto JD , Wei WI , Wood RR , Wu JT , Zhang J , Walker PG , Whittaker C . medRxiv 2021 BACKGROUND: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. METHODS: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. RESULTS: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, but low-income settings were characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. CONCLUSIONS: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. FUNDING: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1). |
Using mortuary and burial data to place COVID-19 in Lusaka, Zambia within a global context
Sheppard RJ , Watson OJ , Pieciak R , Lungu J , Kwenda G , Moyo C , Chanda SL , Barnsley G , Brazeau NF , Gerard-Ursin ICG , Olivera Mesa D , Whittaker C , Gregson S , Okell LC , Ghani AC , MacLeod WB , Del Fava E , Melegaro A , Hines JZ , Mulenga LB , Walker PGT , Mwananyanda L , Gill CJ . Nat Commun 2023 14 (1) 3840 Reported COVID-19 cases and associated mortality remain low in many sub-Saharan countries relative to global averages, but true impact is difficult to estimate given limitations around surveillance and mortality registration. In Lusaka, Zambia, burial registration and SARS-CoV-2 prevalence data during 2020 allow estimation of excess mortality and transmission. Relative to pre-pandemic patterns, we estimate age-dependent mortality increases, totalling 3212 excess deaths (95% CrI: 2104-4591), representing an 18.5% (95% CrI: 13.0-25.2%) increase relative to pre-pandemic levels. Using a dynamical model-based inferential framework, we find that these mortality patterns and SARS-CoV-2 prevalence data are in agreement with established COVID-19 severity estimates. Our results support hypotheses that COVID-19 impact in Lusaka during 2020 was consistent with COVID-19 epidemics elsewhere, without requiring exceptional explanations for low reported figures. For more equitable decision-making during future pandemics, barriers to ascertaining attributable mortality in low-income settings must be addressed and factored into discourse around reported impact differences. |
Results from the second WHO external quality assessment for the molecular detection of respiratory syncytial virus, 2019-2020.
Williams T , Jackson S , Barr I , Bi S , Bhiman J , Ellis J , von Gottberg A , Lindstrom S , Peret T , Rughooputh S , Viegas M , Hirve S , Zambon M , Zhang W , Dia N , Razanazatovo N , Al-Nabet Admh , Abubakar A , Tivane A , Barakat A , Naguib A , Aziz A , Vicari A , Moen A , Govindakarnavar A , Hall A , Darmaa B , Nathalie B , Herring B , Caetano BC , Whittaker B , Baumeister E , Nakouné E , Guthrie E , Inbanathan F , Nair H , Campbell H , Kadjo HA , Oumzil H , Heraud JM , Mott JA , Namulondo J , Leite J , Nahapetyan K , Al Ariqi L , Gazo MHI , Chadha M , Pisareva M , Venter M , Siqueira MM , Lumandas M , Niang M , Albuaini M , Salman M , Oberste S , Srikantiah P , Tang P , Couto P , Smith P , Coyle PV , Dussart P , Nguyen PN , Okada PA , Wijesinghe PR , Samuel R , Brown R , Pebody R , Fasce R , Jha R , Lindstrom S , Gerber S , Potdar V , Dong X , Deng YM . Influenza Other Respir Viruses 2023 17 (1) e13073 Background: External quality assessments (EQAs) for the molecular detection of human respiratory syncytial virus (RSV) are necessary to ensure the standardisation of reliable results. The Phase II, 2019–2020 World Health Organization (WHO) RSV EQA included 28 laboratories in 26 countries. The EQA panel evaluated performance in the molecular detection and subtyping of RSV-A and RSV-B. This manuscript describes the preparation, distribution, and analysis of the 2019–2020 WHO RSV EQA. Methods: Panel isolates underwent whole genome sequencing and in silico primer matching. The final panel included nine contemporary, one historical virus and two negative controls. The EQA panel was manufactured and distributed by the UK National External Quality Assessment Service (UK NEQAS). National laboratories used WHO reference assays developed by the United States Centers for Disease Control and Prevention, an RSV subtyping assay developed by the Victorian Infectious Diseases Reference Laboratory (Australia), or other in-house or commercial assays already in use at their laboratories. Results: An in silico analysis of isolates showed a good match to assay primer/probes. The panel was distributed to 28 laboratories. Isolates were correctly identified in 98% of samples for detection and 99.6% for subtyping. Conclusions: The WHO RSV EQA 2019–2020 showed that laboratories performed at high standards. Updating the composition of RSV molecular EQAs with contemporary strains to ensure representation of circulating strains, and ensuring primer matching with EQA panel viruses, is advantageous in assessing diagnostic competencies of laboratories. Ongoing EQAs are recommended because of continued evolution of mismatches between current circulating strains and existing primer sets. © 2023 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd. |
Impacts of risk assessment data, assumptions, and methods: Considering the evidence for diacetyl and 2,3-pentanedione
Johns DO , Whittaker C , Cox-Ganser JM . Front Public Health 2022 10 972136 The articles published as part of the Frontiers in Public Health research topic, "Investigating exposures and respiratory health in coffee workers" present research findings that better characterize exposures to diacetyl and 2,3-pentanedione and inform our understanding of the health risks posed by these exposures. Although various research groups and organizations have conducted risk assessments to derive occupational exposure limits (OELs) for diacetyl, differences in the data used and assumptions made in these efforts have resulted in a wide range of recommended OELs designed to protect human health. The primary drivers of these differences include the decision to use data from human or animal studies in conducting a quantitative risk assessment, and the application of uncertainty factors (UF) to derive an OEL. This Perspectives paper will discuss the practical implications of these decisions, and present additional commentary on the potential role that the recent investigation of human exposures to relatively low concentrations of α-diketones, specifically diacetyl and 2,3-pentanedione, may play in supporting qualitative or quantitative human health risk assessments. |
Social contact patterns and implications for infectious disease transmission: a systematic review and meta-analysis of contact surveys.
Mousa A , Winskill P , Watson OJ , Ratmann O , Monod M , Ajelli M , Diallo A , Dodd PJ , Grijalva CG , Kiti MC , Krishnan A , Kumar R , Kumar S , Kwok KO , Lanata CF , le Polain de Waroux O , Leung K , Mahikul W , Melegaro A , Morrow CD , Mossong J , Neal EF , Nokes DJ , Pan-Ngum W , Potter GE , Russell FM , Saha S , Sugimoto JD , Wei WI , Wood RR , Wu J , Zhang J , Walker P , Whittaker C . Elife 2021 10 Background: Transmission of respiratory pathogens such as SARS-CoV-2 depends on patterns of contact and mixing across populations. Understanding this is crucial to predict pathogen spread and the effectiveness of control efforts. Most analyses of contact patterns to date have focussed on high-income settings. Methods: Here, we conduct a systematic review and individual-participant meta-analysis of surveys carried out in low- and middle-income countries and compare patterns of contact in these settings to surveys previously carried out in high-income countries. Using individual-level data from 28,503 participants and 413,069 contacts across 27 surveys we explored how contact characteristics (number, location, duration and whether physical) vary across income settings. Results: Contact rates declined with age in high- and upper-middle-income settings, but not in low-income settings, where adults aged 65+ made similar numbers of contacts as younger individuals and mixed with all age-groups. Across all settings, increasing household size was a key determinant of contact frequency and characteristics, with low-income settings characterised by the largest, most intergenerational households. A higher proportion of contacts were made at home in low-income settings, and work/school contacts were more frequent in high-income strata. We also observed contrasting effects of gender across income-strata on the frequency, duration and type of contacts individuals made. Conclusions: These differences in contact patterns between settings have material consequences for both spread of respiratory pathogens, as well as the effectiveness of different non-pharmaceutical interventions. Funding: This work is primarily being funded by joint Centre funding from the UK Medical Research Council and DFID (MR/R015600/1). |
Perchloroethylene and dry cleaning: It's time to move the industry to safer alternatives
Ceballos DM , Fellows KM , Evans AE , Janulewicz PA , Lee EG , Whittaker SG . Front Public Health 2021 9 638082 Perchloroethylene (PERC) is the most common solvent used for dry cleaning in the United States. PERC is a reproductive toxicant, neurotoxicant, potential human carcinogen, and a persistent environmental pollutant. The Environmental Protection Agency is evaluating PERC under the Frank R. Lautenberg Chemical Safety for the 21st Century Act, which amended the Toxic Substances Control Act (amended TSCA), and has mandated that PERC dry cleaning machines be removed from residential buildings. Some local and state programs are also requiring or facilitating transitions to alternative cleaning technologies. However, the potential for these alternatives to harm human health and the environment is not well-understood. This review describes the issues surrounding the use of PERC and alternative solvents for dry cleaning while highlighting the lessons learned from a local government program that transitioned PERC dry cleaners to the safest current alternative: professional wet cleaning. Implications for future public health research and policy are discussed: (1) we must move away from PERC, (2) any transition must account for the economic instability and cultural aspects of the people who work in the industry, (3) legacy contamination must be addressed even after safer alternatives are adopted, and (4) evaluations of PERC alternatives are needed to determine their implications for the long-term health and sustainability of the people who work in the industry. |
Integrating genotypes and phenotypes improves long-term forecasts of seasonal influenza A/H3N2 evolution.
Huddleston J , Barnes JR , Rowe T , Xu X , Kondor R , Wentworth DE , Whittaker L , Ermetal B , Daniels RS , McCauley JW , Fujisaki S , Nakamura K , Kishida N , Watanabe S , Hasegawa H , Barr I , Subbarao K , Barrat-Charlaix P , Neher RA , Bedford T . Elife 2020 9 Seasonal influenza virus A/H3N2 is a major cause of death globally. Vaccination remains the most effective preventative. Rapid mutation of hemagglutinin allows viruses to escape adaptive immunity. This antigenic drift necessitates regular vaccine updates. Effective vaccine strains need to represent H3N2 populations circulating one year after strain selection. Experts select strains based on experimental measurements of antigenic drift and predictions made by models from hemagglutinin sequences. We developed a novel influenza forecasting framework that integrates phenotypic measures of antigenic drift and functional constraint with previously published sequence-only fitness estimates. Forecasts informed by phenotypic measures of antigenic drift consistently outperformed previous sequence- only estimates, while sequence-only estimates of functional constraint surpassed more comprehensive experimentally-informed estimates. Importantly, the best models integrated estimates of both functional constraint and either antigenic drift phenotypes or recent population growth. |
Outbreak of norovirus illness among wildfire evacuation shelter populations - Butte and Glenn Counties, California, November 2018
Karmarkar E , Jain S , Higa J , Fontenot J , Bertolucci R , Huynh T , Hammer G , Brodkin A , Thao M , Brousseau B , Hopkins D , Kelly E , Sheffield M , Henley S , Whittaker H , Herrick RL , Pan CY , Chen A , Kim J , Schaumleffel L , Khwaja Z , Epson E , Chai SJ , Wadford D , Vugia D , Lewis L . MMWR Morb Mortal Wkly Rep 2020 69 (20) 613-617 The Camp Fire, California's deadliest wildfire, began November 8, 2018, and was extinguished November 25 (1). Approximately 1,100 evacuees from the fire sought emergency shelter. On November 10, acute gastroenteritis (AGE) was reported in two evacuation shelters; norovirus illness was suspected, because it is commonly detected in shelter-associated AGE outbreaks. Norovirus is highly contagious and resistant to several disinfectants. Butte County Public Health Department (BCPHD), assisted by the California Department of Public Health (CDPH), initiated active surveillance to identify cases, confirm the etiology, and assess shelter infection prevention and control (IPC) practices to guide recommendations. During November 8-30, a total of 292 patients with AGE were identified among nine evacuation shelters; norovirus was detected in 16 of 17 unique patient stool specimens. Shelter IPC assessments revealed gaps in illness surveillance, isolation practices, cleaning, disinfection, and handwashing. CDPH and BCPHD collaborated with partner agencies to implement AGE screening, institute isolation protocols and 24-hour cleaning services, and promote proper hand hygiene. During disasters with limited resources, damaged infrastructure, and involvement of multiple organizations, establishing shelter disease surveillance and IPC is difficult. However, prioritizing effective surveillance and IPC at shelter activation is necessary to prevent, identify, and contain outbreaks. |
Application of the draft NIOSH Occupational Exposure Banding Process to Bisphenol A: A case study
Hines CJ , Lentz TJ , McKernan L , Rane P , Whittaker C . J Occup Environ Hyg 2018 16 (2) 1-20 Bisphenol A is a commercially important chemical used to make polycarbonate plastic, epoxy resins and other specialty products. Despite an extensive body of in vitro, animal and human observational studies on the effects of exposure to bisphenol A, no authoritative bodies in the U.S. have adopted or recommended occupational exposure limits for bisphenol A. In 2017, the National Institute for Occupational Safety and Health published a Draft process for assigning health-protective occupational exposure bands, i.e. an airborne concentration range, to chemicals lacking an occupational exposure limit. Occupational exposure banding is a systematic process that uses both quantitative and qualitative toxicity information on selected health effect endpoints to assign an occupational exposure band for a chemical. The Draft process proposes three methodological tiers of increasing complexity for assigning an occupational exposure band. We applied Tier 1 (based on the Globally Harmonized System of Classification and Labelling) and Tier 2 (based on authoritative sources/reviews) to assign an occupational exposure band to bisphenol A. Under both Tier 1 and 2, the occupational exposure band for bisphenol A was "E" (<0.01 mg/m(3)), an assignment based on eye damage. "E" is the lowest exposure concentration range, reserved for chemicals with high potential toxicity. If eye damage was excluded in assigning an air concentration exposure range, then bisphenol A would band as "D" (>0.01 to 0.1 mg/m(3)) under Tier 1 (based on reproductive toxicity and respiratory/skin sensitization) and under Tier 2 (based on specific target organ toxicity-repeated exposure). In summary, Tiers 1 and 2 gave the same occupational exposure band for bisphenol A when eye damage was included ("E") or excluded ("D") as an endpoint. |
Pulmonary impairment and risk assessment in a diacetyl-exposed population: Microwave popcorn workers
Park RM , Gilbert SJ , Whittaker C . J Occup Environ Med 2018 60 (6) 496-506 OBJECTIVES: The butter flavoring additive, diacetyl (DA), can cause bronchiolitis obliterans (BO) by inhalation. A risk assessment was performed using data from a microwave popcorn manufacturing plant. METHODS: Current employees' medical history and pulmonary function tests together with air sampling over a 2.7 yr period were used to analyze FEV1 and FEV1/FVC. The exposure responses for declining pulmonary function and for possible early onset of BO were estimated using multiple regression methods. Several exposure metrics were investigated; benchmark dose and excess lifetime risk of impairment were calculated. RESULTS: Forty-six percent of the population had less than 6 mo exposure to DA. Percent-of-predicted FEV1 declined with cumulative exposure (0.40 per ppm-yr, p < 10) and as did percent FEV1/FVC (0.13 per ppm-yr, p = 0.0004). Lifetime respiratory impairment prevalence of one per thousand resulted from 0.005 ppm DA and one per thousand lifetime incidence of impairment was predicted for 0.002 ppm DA. CONCLUSION: DA exposures, often exceeding 1 ppm in the past, place workers at high risk of pulmonary impairment. |
Safe recombinant outer membrane vesicles that display M2e elicit heterologous influenza protection
Watkins HC , Rappazzo CG , Higgins JS , Sun X , Brock N , Chau A , Misra A , Cannizzo JP , King MR , Maines TR , Leifer CA , Whittaker GR , DeLisa MP , Putnam D . Mol Ther 2017 25 (4) 989-1002 Recombinant, Escherichia coli-derived outer membrane vesicles (rOMVs), which display heterologous protein subunits, have potential as a vaccine adjuvant platform. One drawback to rOMVs is their lipopolysaccharide (LPS) content, limiting their translatability to the clinic due to potential adverse effects. Here, we explore a unique rOMV construct with structurally remodeled lipids containing only the lipid IVa portion of LPS, which does not stimulate human TLR4. The rOMVs are derived from a genetically engineered B strain of E. coli, ClearColi, which produces lipid IVa, and which was further engineered in our laboratory to hypervesiculate and make rOMVs. We report that rOMVs derived from this lipid IVa strain have substantially attenuated pyrogenicity yet retain high levels of immunogenicity, promote dendritic cell maturation, and generate a balanced Th1/Th2 humoral response. Additionally, an influenza A virus matrix 2 protein-based antigen displayed on these rOMVs resulted in 100% survival against a lethal challenge with two influenza A virus strains (H1N1 and H3N2) in mice with different genetic backgrounds (BALB/c, C57BL/6, and DBA/2J). Additionally, a two-log reduction of lung viral titer was achieved in a ferret model of influenza infection with human pandemic H1N1. The rOMVs reported herein represent a potentially safe and simple subunit vaccine delivery platform. |
Occupational Exposures to New Drycleaning Solvents: High-flashpoint Hydrocarbons and Butylal
Ceballos DM , Whittaker SG , Lee EG , Roberts J , Streicher R , Gong FN , Broadwater W , Broadwater K . J Occup Environ Hyg 2016 13 (10) 0 The drycleaning industry is moving away from using perchloroethylene. Occupational exposures to two alternative drycleaning solvents, butylal and high-flashpoint hydrocarbons, have not been well-characterized. We evaluated four drycleaning shops that used these alternative solvents. The shops were staffed by Korean- and Cantonese-speaking owners, and Korean-, Cantonese-, and Spanish-speaking employees. Because most workers had limited English proficiency we used language services in our evaluations. In two shops we collected personal and area air samples for butylal. We also collected air samples for formaldehyde and butanol, potential hydrolysis products of butylal. Because there are no occupational exposure limits for butylal, we assessed employee health risks using control banding tools. In the remaining two shops we collected personal and area air samples for high-flashpoint hydrocarbon solvents. In all shops the highest personal airborne exposures occurred when workers loaded and unloaded the drycleaning machines and pressed drycleaned fabrics. The air concentrations of formaldehyde and butanol in the butylal shops were well below occupational exposure limits. Likewise, the air concentrations of high-flashpoint hydrocarbons were also well below occupational exposure limits. However, we saw potential skin exposures to these chemicals. We provided recommendations on appropriate work practices and the selection and use of personal protective equipment. These recommendations were consistent with those derived using control banding tools for butylal. However, there is insufficient toxicological and health information to determine the safety of butylal in occupational settings. Independent evaluation of the toxicological properties of these alternative drycleaning solvents, especially butylal, is urgently needed. |
The Next Generation of Risk Assessment Multiyear Study- Highlights of Findings, Applications to Risk Assessment and Future Directions.
Cote I , Andersen ME , Ankley GT , Barone S , Birnbaum LS , Boekelheide K , Bois FY , Burgoon LD , Chiu WA , Crawford-Brown D , Crofton KM , DeVito M , Devlin RB , Edwards SW , Guyton KZ , Hattis D , Judson RS , Knight D , Krewski D , Lambert J , Maull EA , Mendrick D , Paoli GM , Patel CJ , Perkins EJ , Poje G , Portier CJ , Rusyn I , Schulte PA , Simeonov A , Smith MT , Thayer KA , Thomas RS , Thomas R , Tice RR , Vandenberg JJ , Villeneuve DL , Wesselkamper S , Whelan M , Whittaker C , White R , Xia M , Yauk C , Zeise L , Zhao J , DeWoskin RS . Environ Health Perspect 2016 124 (11) 1671-1682 BACKGROUND: The Next Generation (NexGen) of Risk Assessment effort is a multiyear collaboration among several organizations evaluating new, potentially more efficient molecular, computational and systems biology approaches to risk assessment. This paper summarizes our findings, suggests applications to risk assessment, and identifies strategic research directions. OBJECTIVE: Our specific objectives were to test whether advanced biological data and methods could better inform our understanding of public health risks posed by environmental exposures. METHODS: New data and methods were applied and evaluated for use in hazard identification and dose-response assessment. Biomarkers of exposure and effect, and risk characterization were also examined. Consideration was given to various decision contexts with increasing regulatory and public health impacts. Data types included transcriptomics, genomics, and proteomics; methods included molecular epidemiology and clinical studies, bioinformatic knowledge mining, pathway and network analyses, short-duration in vivo and in vitro bioassays, and quantitative structure activity relationship modeling. DISCUSSION: NexGen has advanced our ability to apply new science by more rapidly identifying chemicals and exposures of potential concern, helping characterize mechanisms of action that influence conclusions about causality, exposure-response relationships, susceptibility and cumulative risk, and by elucidating new biomarkers of exposure and effects. Additionally, NexGen has fostered extensive discussion among risk scientists and managers and improved confidence in interpreting and applying new data streams. CONCLUSIONS: While considerable uncertainties remain, thoughtful application of new knowledge to risk assessment appears reasonable for augmenting major scope assessments, forming the basis for or augmenting limited scope assessments, and for prioritization and screening of very data limited chemicals. |
Strategies and approaches to vector control in nine malaria-eliminating countries: a cross-case study analysis
Smith Gueye C , Newby G , Gosling RD , Whittaker MA , Chandramohan D , Slutsker L , Tanner M . Malar J 2016 15 (1) 2 BACKGROUND: There has been progress towards malaria elimination in the last decade. In response, WHO launched the Global Technical Strategy (GTS), in which vector surveillance and control play important roles. Country experiences in the Eliminating Malaria Case Study Series were reviewed to identify success factors on the road to elimination using a cross-case study analytic approach. METHODS: Reports were included in the analysis if final English language draft reports or publications were available at the time of analysis (Bhutan, Cape Verde, Malaysia, Mauritius, Namibia, Philippines, Sri Lanka, Turkey, Turkmenistan). A conceptual framework for vector control in malaria elimination was developed, reviewed, formatted as a matrix, and case study data was extracted and entered into the matrix. A workshop was convened during which participants conducted reviews of the case studies and matrices and arrived at a consensus on the evidence and lessons. The framework was revised and a second round of data extraction, synthesis and summary of the case study reports was conducted. RESULTS: Countries implemented a range of vector control interventions. Most countries aligned with integrated vector management, however its impact was not well articulated. All programmes conducted entomological surveillance, but the response (i.e., stratification and targeting of interventions, outbreak forecasting and strategy) was limited or not described. Indoor residual spraying (IRS) was commonly used by countries. There were several examples of severe reductions or halting of IRS coverage and subsequent resurgence of malaria. Funding and operational constraints and poor implementation had roles. Bed nets were commonly used by most programmes; coverage and effectiveness were either not measured or not articulated. Larval control was an important intervention for several countries, preventing re-introduction, however coverage and impact on incidence were not described. Across all interventions, coverage indicators were incomparable, and the rationale for which tools were used and which were not used appeared to be a function of the availability of funding, operational issues and cost instead of evidence of effectiveness to reduce incidence. CONCLUSIONS: More work is required to fill gaps in programme guidance, clarify the best methods for choosing and targeting vector control interventions, and support to measure cost, cost-effectiveness and cost-benefit of vector surveillance and control interventions. |
State-of-the-science: the evolution of occupational exposure limit derivation and application
Maier A , Lentz TJ , MacMahon KL , McKernan LT , Whittaker C , Schulte PA . J Occup Environ Hyg 2015 12 Suppl 1 S4-6 Occupational exposure limits (OELs) are a critical component of the risk assessment and risk management process and their use remains a staple of occupational hygiene practice. There are dozens of organizations and agencies that derive OELs worldwide. Yet, while most of these groups describe their administrative procedures as well as the rationale for the derivation of OELs for individual substances, few provide equally complete documentation of the underlying scientific methodology for conducting the quantitative risk assessment employed in OEL development. The paucity of written descriptions of OEL development methodology has resulted in a lack of transparency related to implementation of important scientific principles for OEL development and inconsistent practices for OEL development within and among organizations. The absence of such transparency limits the opportunities for international harmonization of existing values and OEL setting practices among organizations. | Given these and other challenges, the National Institute for Occupational Safety and Health (NIOSH) began an effort to identify and characterize leading issues pertaining to OELs and their development through research which culminated in a collection of articles focused on each key issue. Those articles and the key issues they explore comprise this supplement of the Journal of Occupational and Environmental Hygiene. Utilizing subject matter expertise from researchers and thought leaders in the occupational hygiene profession and affiliated fields of environmental public health, the goal of this effort is to describe the issues related to education and communication of science principles and to understand how they can be incorporated into (and thereby impact) the practices of OEL development and interpretation. Focusing specifically on the state-of-the-science in the fields of exposure science, occupational hygiene, risk assessment, and toxicology this effort sought to provide a clear description of how advances in these research areas can contribute to the practice of OEL setting—by reviewing the methods used for most OELs that are currently available as well as new methods that are actively being incorporated in the OEL process. An essential topic included within the set of complementary and interrelated articles dedicated to this pursuit is the consideration and interpretation of OELs in the context of evolving risk management practices. The articles are intended to serve as a current critical review of occupational risk assessment methods that will enable occupational hygiene professionals to have a clear understanding of the science methods incorporated in the OELs they develop or use. A brief introduction to each article in this collection is provided in the following paragraphs. |
Considerations for Using Genetic and Epigenetic Information in Occupational Health Risk Assessment and Standard Setting.
Schulte PA , Whittaker C , Curran CP . J Occup Environ Hyg 2015 12 Suppl 1 S69-81 Risk assessment forms the basis for both occupational health decision-making and the development of occupational exposure limits (OELs). Although genetic and epigenetic data have not been widely used in risk assessment and ultimately, standard setting, it is possible to envision such uses. A growing body of literature demonstrates that genetic and epigenetic factors condition biological responses to occupational and environmental hazards or serve as targets of them. This presentation addresses the considerations for using genetic and epigenetic information in risk assessments, provides guidance on using this information within the classic risk assessment paradigm, and describes a framework to organize thinking about such uses. The framework is a 4 x 4 matrix involving the risk assessment functions (hazard identification, dose-response modeling, exposure assessment, and risk characterization) on one axis and inherited and acquired genetic and epigenetic data on the other axis. The cells in the matrix identify how genetic and epigenetic data can be used for each risk assessment function. Generally, genetic and epigenetic data might be used as endpoints in hazard identification, as indicators of exposure, as effect modifiers in exposure assessment and dose-response modeling, as descriptors of mode of action, and to characterize toxicity pathways. Vast amounts of genetic and epigenetic data may be generated by high-throughput technologies. These data can be useful for assessing variability and reducing uncertainty in extrapolations, and they may serve as the foundation upon which identification of biological perturbations would lead to a new paradigm of toxicity pathway-based risk assessments. |
Historical context and recent advances in exposure-response estimation for deriving occupational exposure limits
Wheeler MW , Park RM , Bailer AJ , Whittaker C . J Occup Environ Hyg 2015 12 Suppl 1 0 Virtually no occupational exposure standards specify the level of risk for the prescribed exposure, and most occupational exposure limits are not based on quantitative risk assessment (QRA) at all. Wider use of QRA could improve understanding of occupational risks while increasing focus on identifying exposure concentrations conferring acceptably low levels of risk to workers. Exposure-response modeling between a defined hazard and the biological response of interest is necessary to provide a quantitative foundation for risk-based occupational exposure limits; and there has been considerable work devoted to establishing reliable methods quantifying the exposure-response relationship including methods of extrapolation below the observed responses. We review of several exposure-response modeling methods available for QRA, and demonstrate their utility with simulated data sets. |
The challenge of artemisinin resistance can only be met by eliminating Plasmodium falciparum malaria across the Greater Mekong subregion
Smith Gueye C , Newby G , Hwang J , Phillips AA , Whittaker M , MacArthur JR , Gosling RD , Feachem RG . Malar J 2014 13 286 Artemisinin-based combinations are currently the most effective anti-malarials and, in addition to vector control, have led to significant declines in malaria morbidity and mortality. However, foci of artemisinin drug resistance have been identified in the Greater Mekong subregion (GMS) of the Asia Pacific, threatening the major gains made in malaria control and potentially creating a parasite pool that is more difficult to treat and eliminate. Efforts are underway to halt the spread of artemisinin resistance, including coordination of activities and funding, and identification of areas of suspected artemisinin resistance, now using a newly identified molecular marker. However, targeting resources to the containment of resistant parasites is likely inefficient and monitoring impact is challenging. A more sustainable solution is the rapid elimination of all Plasmodium falciparum parasites from the GMS. This strategy is more efficient for several reasons. First, a subregional strategy is in line with current commitment to elimination and will build upon the existing national political support for elimination as well as enhancing collaboration among countries. Second, the challenge of human mobility in the GMS is subregional in scope and requires a harmonized elimination strategy. Third, countries will need to improve and intensify malaria operations to reach elimination, and this will be a singular goal across the subregion. Rallying around the goal of P. falciparum elimination will not only utilize existing regional bodies to catalyze political and funding support, but will also leverage the funding already in place to achieve this subregional goal. |
Association between alcohol and cardiovascular disease: Mendelian randomisation analysis based on individual participant data.
Holmes MV , Dale CE , Zuccolo L , Silverwood RJ , Guo Y , Ye Z , Prieto-Merino D , Dehghan A , Trompet S , Wong A , Cavadino A , Drogan D , Padmanabhan S , Li S , Yesupriya A , Leusink M , Sundstrom J , Hubacek JA , Pikhart H , Swerdlow DI , Panayiotou AG , Borinskaya SA , Finan C , Shah S , Kuchenbaecker KB , Shah T , Engmann J , Folkersen L , Eriksson P , Ricceri F , Melander O , Sacerdote C , Gamble DM , Rayaprolu S , Ross OA , McLachlan S , Vikhireva O , Sluijs I , Scott RA , Adamkova V , Flicker L , Bockxmeer FM , Power C , Marques-Vidal P , Meade T , Marmot MG , Ferro JM , Paulos-Pinheiro S , Humphries SE , Talmud PJ , Mateo Leach I , Verweij N , Linneberg A , Skaaby T , Doevendans PA , Cramer MJ , Harst Pv , Klungel OH , Dowling NF , Dominiczak AF , Kumari M , Nicolaides AN , Weikert C , Boeing H , Ebrahim S , Gaunt TR , Price JF , Lannfelt L , Peasey A , Kubinova R , Pajak A , Malyutina S , Voevoda MI , Tamosiunas A , Maitland-van der Zee AH , Norman PE , Hankey GJ , Bergmann MM , Hofman A , Franco OH , Cooper J , Palmen J , Spiering W , Jong PA , Kuh D , Hardy R , Uitterlinden AG , Ikram MA , Ford I , Hypponen E , Almeida OP , Wareham NJ , Khaw KT , Hamsten A , Husemoen LL , Tjonneland A , Tolstrup JS , Rimm E , Beulens JW , Verschuren WM , Onland-Moret NC , Hofker MH , Wannamethee SG , Whincup PH , Morris R , Vicente AM , Watkins H , Farrall M , Jukema JW , Meschia J , Cupples LA , Sharp SJ , Fornage M , Kooperberg C , LaCroix AZ , Dai JY , Lanktree MB , Siscovick DS , Jorgenson E , Spring B , Coresh J , Li YR , Buxbaum SG , Schreiner PJ , Ellison RC , Tsai MY , Patel SR , Redline S , Johnson AD , Hoogeveen RC , Hakonarson H , Rotter JI , Boerwinkle E , Bakker PI , Kivimaki M , Asselbergs FW , Sattar N , Lawlor DA , Whittaker J , Davey Smith G , Mukamal K , Psaty BM , Wilson JG , Lange LA , Hamidovic A , Hingorani AD , Nordestgaard BG , Bobak M , Leon DA , Langenberg C , Palmer TM , Reiner AP , Keating BJ , Dudbridge F , Casas JP . BMJ 2014 349 g4164 OBJECTIVE: To use the rs1229984 variant in the alcohol dehydrogenase 1B gene (ADH1B) as an instrument to investigate the causal role of alcohol in cardiovascular disease. DESIGN: Mendelian randomisation meta-analysis of 56 epidemiological studies. PARTICIPANTS: 261 991 individuals of European descent, including 20 259 coronary heart disease cases and 10 164 stroke events. Data were available on ADH1B rs1229984 variant, alcohol phenotypes, and cardiovascular biomarkers. MAIN OUTCOME MEASURES: Odds ratio for coronary heart disease and stroke associated with the ADH1B variant in all individuals and by categories of alcohol consumption. RESULTS: Carriers of the A-allele of ADH1B rs1229984 consumed 17.2% fewer units of alcohol per week (95% confidence interval 15.6% to 18.9%), had a lower prevalence of binge drinking (odds ratio 0.78 (95% CI 0.73 to 0.84)), and had higher abstention (odds ratio 1.27 (1.21 to 1.34)) than non-carriers. Rs1229984 A-allele carriers had lower systolic blood pressure (-0.88 (-1.19 to -0.56) mm Hg), interleukin-6 levels (-5.2% (-7.8 to -2.4%)), waist circumference (-0.3 (-0.6 to -0.1) cm), and body mass index (-0.17 (-0.24 to -0.10) kg/m(2)). Rs1229984 A-allele carriers had lower odds of coronary heart disease (odds ratio 0.90 (0.84 to 0.96)). The protective association of the ADH1B rs1229984 A-allele variant remained the same across all categories of alcohol consumption (P=0.83 for heterogeneity). Although no association of rs1229984 was identified with the combined subtypes of stroke, carriers of the A-allele had lower odds of ischaemic stroke (odds ratio 0.83 (0.72 to 0.95)). CONCLUSIONS: Individuals with a genetic variant associated with non-drinking and lower alcohol consumption had a more favourable cardiovascular profile and a reduced risk of coronary heart disease than those without the genetic variant. This suggests that reduction of alcohol consumption, even for light to moderate drinkers, is beneficial for cardiovascular health. |
Text4baby: development and implementation of a national text messaging health information service
Whittaker R , Matoff-Stepp S , Meehan J , Kendrick J , Jordan E , Stange P , Cash A , Meyer P , Baitty J , Johnson P , Ratzan S , Rhee K . Am J Public Health 2012 102 (12) 2207-13 Text4baby is the first free national health text messaging service in the United States that aims to provide timely information to pregnant women and new mothers to help them improve their health and the health of their babies. Here we describe the development of the text messages and the large public-private partnership that led to the national launch of the service in 2010. Promotion at the local, state, and national levels produced rapid uptake across the United States. More than 320,000 people enrolled with text4baby between February 2010 and March 2012. Further evaluations of the effectiveness of the service are ongoing; however, important lessons can be learned from its development and uptake. (Am J Public Health. Published online ahead of print October 18, 2012: e1-e7. doi:10.2105/AJPH.2012.300736). |
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