In the United States (US), biosafety and biosecurity oversight of research on viruses is being reappraised. Safety in virology research is paramount and oversight frameworks should be reviewed periodically. Changes should be made with care, however, to avoid impeding science that is essential for rapidly reducing and responding to pandemic threats as well as addressing more common challenges caused by infectious diseases. Decades of research uniquely positioned the US to be able to respond to the COVID-19 crisis with astounding speed, delivering life-saving vaccines within a year of identifying the virus. We should embolden and empower this strength, which is a vital part of protecting the health, economy, and security of US citizens. Herein, we offer our perspectives on priorities for revised rules governing virology research in the US.
Hospital-acquired infections, caused by ESKAPE bacteria, are a challenging global public health concern, in part due to the emergence of drug-resistant strains. While profiling a diverse set of compounds for in vitro activity versus this class of bacteria, we noted that the benzothiophene JSF-2827 exhibited promising antibacterial activity against Enterococcus faecium. A hit evolution campaign ensued, involving the design, synthesis, and biological assay of analogues designed to address early issues such as a short mouse liver microsome half-life and a modest mouse pharmacokinetic profile. Among these derivatives, JSF-3269 was found to exhibit an enhanced profile and in vivo efficacy in an immunocompetent mouse model of acute, drug-resistant E. faecium infection. The findings suggest a rationale for the further evolution of this promising series to afford a novel therapeutic strategy to treat drug-resistant E. faecium infection.
Chapter 19 Where Is the Governance of Dual-Use Science Going? Nancy Connell, Nancy Connell Rutgers New Jersey Medical School, Newark, NJ, USASearch for more papers by this authorGigi Gronvall, Gigi Gronvall Center for Health Security, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USASearch for more papers by this author Nancy Connell, Nancy Connell Rutgers New Jersey Medical School, Newark, NJ, USASearch for more papers by this authorGigi Gronvall, Gigi Gronvall Center for Health Security, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USASearch for more papers by this author Book Editor(s):Lijun Shang, Lijun Shang Biological Security Research Centre, School of Human Sciences, London Metropolitan University, London, UKSearch for more papers by this authorWeiwen Zhang, Weiwen Zhang Center for Biosafety Research and Strategy, Tianjin University, Tianjin, ChinaSearch for more papers by this authorMalcolm Dando, Malcolm Dando School of Social Sciences, University of Bradford, Bradford, UKSearch for more papers by this author First published: 01 March 2024 https://doi.org/10.1002/9781394189045.ch19 AboutPDFPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShareShare a linkShare onEmailFacebookTwitterLinkedInRedditWechat Summary Governance is the mechanism to ensure accountability, providing oversight to ensure that risks are adequately prevented and mitigated. Thus, biosafety and biosecurity are central to the mechanism of governance. This chapter begins with a brief discussion of rapidly emerging technologies such as genetic manipulation and artificial intelligence. The collective process of creating an international governance mechanism for dual-use research requires standardisation of language and concepts. The chapter describes the value of frameworks to help clarify and standardise the approach being used. International, national and local oversight mechanisms, including monitoring of advancing technologies, have begun to populate agencies and institutions whose remit covers dual-use governance. The collective process of creating an international governance mechanism for dual-use research requires standardisation of language and concepts. Applied research into biosafety and biosecurity practices can be used to standardise methodologies across regions as appropriate and progress our ability to appropriately manage risks. References Center for AI Safety . ( 2023 ) Statement on AI Risk . https://www.safe.ai/statement-on-ai-risk . Google Scholar US Department of Energy. ( 2023 ) Manhattan Project Background Information and Preservation Work . https://www.energy.gov/lm/manhattan-project-background-information-and-preservation-work . Google Scholar US Department of Health and Human Services, N.I.o.H . ( 2019 ). NIH Guidelines for Research Involving Recombiannt or Synthetic Nucleic Acid Molecules . https://osp.od.nih.gov/wp-content/uploads/NIH_Guidelines.pdf . Google Scholar Kwik , G. et al ( 2003 ) Biosecurity: responsible stewardship of bioscience in an age of catastrophic terrorism . Biosecurity and Bioterrorism: Biodefense Strategy, Practice, and Science , 1 ( 1 ), 27 – 35 . 10.1089/15387130360514805 PubMedGoogle Scholar Bowman , K. et al ( 2020 ) Assessing the risks and benefits of advances in science and technology: exploring the potential of qualitative frameworks . Health Secure , 18 ( 3 ), 186 – 194 . 10.1089/hs.2019.0134 PubMedWeb of Science®Google Scholar Office for Disarmament Affairs . ( 2023 ) Biological Weapons Convention , United Nations , New York . Google Scholar Pugwash Council . ( 2023 ) Pugwash Conferences on Science and World Affairs , Pugwash , Rome . Google Scholar Agency , I. A. E. ( 2023 ) International Atomic Energy Agency , IAEA , Vienna . Google Scholar World Health Organization . ( 2022 ) The Global Guidance for the Responsible Use of the Life Sciences: Mitigating Biorisks and Governing Dual-Use Research , WHO , Geneva . Google Scholar iGEM Foundation . ( 2023 ) The International Genetic Engineering Machine Competition . https://IGEM.ORG . Google Scholar Sundaram , L. S. ( 2021 ) Biosafety in DIY-bio laboratories: from hype to policy: discussions about regulating DIY biology tend to ignore the extent of self-regulation and oversight of DIY laboratories . EMBO Reports , 22 ( 4 ), e52506 . 10.15252/embr.202152506 CASPubMedWeb of Science®Google Scholar Voeneky , S. et al ( 2018 ) Human rights and legitimate governance of existential and global catastrophic risks , Human Rights, Democracy, and Legitimacy in a World of Disorder , Cambridge University Press , Cambridge , 139 – 162 . Google Scholar Jasanoff , S. ( 2015 ) Dreamscapes of Modernity: Sociotechnical Imaginaries and the Fabrication of Power , University of Chicago Press , Chicago . 10.7208/chicago/9780226276663.001.0001 Google Scholar National Academies of Sciences, Engineering, and Medicine . ( 2018 ) Governance of Dual Use Research in the Life Sciences: Advancing Global Consensus on Research Oversight: Proceedings of a Workshop , The National Academies Press , Washington . Google Scholar US Departmenrt of Health and Human Services . ( 2023 ) National Scientific Advisory Board on Biosecurity , Washington, D.C , National Institutes of Health (Office of Science Policy) . Google Scholar Himmel , M. and EU Non-proliferation and Disarmament Consortium . ( 2019 ) Emerging Dual-Use Technologies in the Life Scinces: Challenges and Policy Recommendations on Expeort Control , Stockholm International Peace Research Institute , Solna . Google Scholar Government of Canada, P.H.A.o.C . ( 2018 ) Canadian Biosafety Guideline – Dual-Use in Life Science Research , Public Health Agency of Canada , Ottawa . Google Scholar Bipartisan Commission on Biodefense . ( 2023 ) Pathogens Project: Creating the Framework for Tomorrow's Pathogen Research , Bulletin of the Atomic Scientists , Geneva . Google Scholar Lowen , A. C. et al ( 2023 ) Oversight of pathogen research must be carefully calibrated and clearly defined . mSphere , 8 ( 2 ), e0006623 . 10.1128/msphere.00066-23 PubMedWeb of Science®Google Scholar Evans , S. W. et al ( 2020 ) Embrace experimentation in biosecurity governance . Science , 368 ( 6487 ), 138 – 140 . 10.1126/science.aba2932 CASPubMedWeb of Science®Google Scholar Essentials of Biological Security: A Global Perspective ReferencesRelatedInformation
How have biosecurity and biosafety developed during the twenty-first century – the “Century of Biosecurity” – and how can oversight and governance of this field be improved? This chapter describes rapid advances in biology and how they can lead to misapplication, from the anthrax biohazard, to the availability of DNA studies on a large scale, to AI’s use of big data today.
Rickettsia is a genus of Gram-negative bacteria that has for centuries caused large-scale morbidity and mortality. In recent years, the resurgence of rickettsial diseases as a major cause of pyrexias of unknown origin, bioterrorism concerns, vector movement, and concerns over drug resistance is driving a need to identify novel treatments for these obligate intracellular bacteria. Utilizing an uvGFP plasmid reporter, we developed a screen for identifying anti-rickettsial small molecule inhibitors using Rickettsia canadensis as a model organism. The screening data were utilized to train a Bayesian model to predict growth inhibition in this assay. This two-pronged methodology identified anti-rickettsial compounds, including duartin and JSF-3204 as highly specific, efficacious, and noncytotoxic compounds. Both molecules exhibited in vitro growth inhibition of R. prowazekii, the causative agent of epidemic typhus. These small molecules and the workflow, featuring a high-throughput phenotypic screen for growth inhibitors of intracellular Rickettsia spp. and machine learning models for the prediction of growth inhibition of an obligate intracellular Gram-negative bacterium, should prove useful in the search for new therapeutic strategies to treat infections from Rickettsia spp. and other obligate intracellular bacteria.
Health SecurityVol. 19, No. 4 CommentaryBiosafety Professionals: A Role in the Pandemic Response TeamKelsey Lane Warmbrod, Jennifer Cole, C. Matthew Sharkey, Aparupa Sengupta, Nancy Connell, Rocco Casagrande, and Patricia DelarosaKelsey Lane WarmbrodKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, Jennifer ColeKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, C. Matthew SharkeyKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, Aparupa SenguptaKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, Nancy ConnellAddress correspondence to: Nancy Connell, PhD, Contributing Scholar, Johns Hopkins Center for Health Security, 621 East Pratt St, Suite 210, Baltimore, MD 21202 E-mail Address: NancyConnell@jhu.eduKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, Rocco CasagrandeKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this author, and Patricia DelarosaKelsey Lane Warmbrod, MS, MPH, is a Senior Analyst and Nancy Connell, PhD, is a Contributing Scholar; both at the Johns Hopkins Center for Health Security, Baltimore, MD. Jennifer Cole, PhD, is a Research Fellow, Department of Geography, Centre for Research into Sustainability, Royal Holloway University of London, Egham, UK. C. Matthew Sharkey, PhD, is a Biologist, Office of the Assistant Secretary for Preparedness and Response, US Department of Health and Human Services, Washington, DC. Aparupa Sengupta, PhD, MS, MSc, RBP (ABSA), is Assistant Director and Campus Biosafety-Biosecurity Officer, Environmental Health and Safety, University of California Merced, Merced, CA. Rocco Casagrande, PhD, is Director, Gryphon Scientific, Takoma Park, MD. Patricia Delarosa, PhD, CBSP (ABSA), CTM (ATAP), is an Adjunct Associate Professor, Department of Microbiology and Immunology, Center for Global Health Science and Security, Georgetown University, Washington, DC. The findings and conclusions in this publication are those of the authors and should not be construed to represent any official US Department of Health and Human Services or US government determination or policy.Search for more papers by this authorPublished Online:16 Aug 2021https://doi.org/10.1089/HS.2021.0015AboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View articleFiguresReferencesRelatedDetailsCited byConcepts to Bolster Biorisk Management Robert August Dettmann, Ryan Ritterson, Erin Lauer, and Rocco Casagrande17 October 2022 | Health Security, Vol. 20, No. 5Experiences During the COVID-19 Pandemic: A Survey of Biosafety Professionals David Gillum, Henry Wyneken, Jennifer Fletcher, Karl Nubbe, and Kathleen M. Vogel14 September 2022 | Applied Biosafety, Vol. 27, No. 3 Volume 19Issue 4Aug 2021 InformationCopyright 2021, Mary Ann Liebert, Inc., publishersTo cite this article:Kelsey Lane Warmbrod, Jennifer Cole, C. Matthew Sharkey, Aparupa Sengupta, Nancy Connell, Rocco Casagrande, and Patricia Delarosa.Biosafety Professionals: A Role in the Pandemic Response Team.Health Security.Aug 2021.454-458.http://doi.org/10.1089/HS.2021.0015Published in Volume: 19 Issue 4: August 16, 2021KeywordsCOVID-19Biosafety protectionEpidemic management/responseFirst respondersNational strategy/policyRisk communicationPDF download
One of the lessons learned from the coronavirus disease 2019 (COVID-19) pandemic is the utility of an early, flexible, and rapidly deployable disease screening and detection response. The largely uncontrolled spread of the pandemic in the United States exposed a range of planning and implementation shortcomings, which, if they had been in place before the pandemic emerged, may have changed the trajectory. Disease screening by detection dogs show great promise as a noninvasive, efficient, and cost-effective screening method for COVID-19 infection. We explore evidence of their use in infectious and chronic diseases; the training, oversight, and resources required for implementation; and potential uses in various settings. Disease detection dogs may contribute to the current and future public health pandemics; however, further research is needed to extend our knowledge and measurement of their effectiveness and feasibility as a public health intervention tool, and efforts are needed to ensure public and political support.
Antibody tests for detecting past infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have many uses for public health decision making, but demand has largely come from individual consumers. This review focuses on the individual relevance of antibody tests: their accuracy in detecting prior infection, what past SARS-CoV-2 infection can currently infer about future immunity or possible medical sequelae, and the potential future importance of antibody tests for vaccine selection and medical screening. Given uncertainty about the antibody tests (quality, accuracy level, positive predictive value) and what those tests might indicate immunologically (durability of antibodies and necessity for protection from reinfection), seropositive test results should not be used to inform individual decision making, and antibody testing should remain a tool of public health at this time.
We present the application of Bayesian modeling to identify chemical tools and/or drug discovery entities pertinent to drug-resistant Staphylococcus aureus infections. The quinoline JSF-3151 was predicted by modeling and then empirically demonstrated to be active against in vitro cultured clinical methicillin- and vancomycin-resistant strains while also exhibiting efficacy in a mouse peritonitis model of methicillin-resistant S. aureus infection. We highlight the utility of an intrabacterial drug metabolism (IBDM) approach to probe the mechanism by which JSF-3151 is transformed within the bacteria. We also identify and then validate two mechanisms of resistance in S. aureus: one mechanism involves increased expression of a lipocalin protein, and the other arises from the loss of function of an azoreductase. The computational and experimental approaches, discovery of an antibacterial agent, and elucidated resistance mechanisms collectively hold promise to advance our understanding of therapeutic regimens for drug-resistant S. aureus.
Serology (antibody) tests to detect previous SARS-CoV-2 infection have been in high demand from the beginning of the COVID-19 pandemic. The initial shortage of diagnostic tests coupled with asymptomatic infections led to a significant demand for serology tests to identify past infections.
Health SecurityVol. 18, No. 6 CommentaryFree AccessGeoffrey Rose's Strategy of Prevention Applied to COVID-19William Halperin, Michel A. Ibrahim, and Nancy ConnellWilliam HalperinWilliam Halperin, MD, DrPH, MPH, is a Professor, Rutgers Biomedical and Health Science, Biostatistics and Epidemiology, Rutgers School of Public Health, Newark, NJ. Michel A. Ibrahim, MD, is a Professor Emeritus and Nancy Connell, PhD, is a Senior Scientist, Center for Health Security, and a Professor, Department of Environmental Health and Engineering; both at the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.Search for more papers by this author, Michel A. IbrahimWilliam Halperin, MD, DrPH, MPH, is a Professor, Rutgers Biomedical and Health Science, Biostatistics and Epidemiology, Rutgers School of Public Health, Newark, NJ. Michel A. Ibrahim, MD, is a Professor Emeritus and Nancy Connell, PhD, is a Senior Scientist, Center for Health Security, and a Professor, Department of Environmental Health and Engineering; both at the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.Search for more papers by this author, and Nancy ConnellAddress correspondence to: Nancy Connell, PhD, Senior Scholar, Professor, Johns Hopkins Center for Health Security, 621 East Pratt Street, Suite 210, Baltimore, MD 21202 E-mail Address: [email protected]William Halperin, MD, DrPH, MPH, is a Professor, Rutgers Biomedical and Health Science, Biostatistics and Epidemiology, Rutgers School of Public Health, Newark, NJ. Michel A. Ibrahim, MD, is a Professor Emeritus and Nancy Connell, PhD, is a Senior Scientist, Center for Health Security, and a Professor, Department of Environmental Health and Engineering; both at the Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.Search for more papers by this authorPublished Online:14 Dec 2020https://doi.org/10.1089/hs.2020.0037AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookXLinked InRedditEmail While there is consensus for the use of personal protective equipment and other measures for the prevention of transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in high-risk situations, such as aerosol-generating medical procedures, there is a divergence of opinion and enthusiasm for measures such as social distancing, cloth masks, and other recommendations in low-risk situations. The insights of epidemiologist Geoffrey Rose1 on sick and high-risk populations may be helpful. In its simplest form, his concept can be explained as follows: the high-risk subpopulation—such as elderly people with preexisting cardiac or pulmonary conditions—may contribute a lesser share to the outcome (eg, infection, death) than a low-risk subpopulation would. This is simply because of the sheer larger number of persons in the low-risk subpopulation. Consider, for example, a population of 1,000 persons, with 100 in a high-risk subpopulation and 900 in a low-risk subpopulation, and a rate of infection 4 times as high in the high-risk subpopulation as in the low-risk subpopulation; their rates of infection are 20% and 5%, respectively. In this hypothetical scenario, the high-risk subpopulation contributes 20 cases to the outcome compared to 45 cases from the low-risk subpopulation.Similarly, epidemiologist Leon Gordis2 demonstrated that for a typical risk factor, hypertension, that expresses itself on a continuum from the lowest to the highest rather than a dichotomy of high and low risk, that a large fraction of a population with moderate elevation of blood pressure accounts for more adverse outcomes than the small fraction of the population with higher blood pressures. These concepts represent an intellectual bridge between risk assessment and risk management. Rose also believed that the same levels of resources dedicated to individuals at high risk cannot be provided to a much larger population of individuals at low risk. His solution is a population-based preventive medicine approach for the larger low-risk subpopulation of the population to supplement the more intensive interventions commonly used for the high-risk subpopulation of the population. An example of a population-based approach is media advertising for smoking cessation.Like the noncommunicable diseases previously mentioned, COVID-19 infection rates vary depending on high or low risk of exposure. An example of high-risk exposure is healthcare workers exposed to aerosol-generating procedures commonly used in intensive care units and emergency departments. In contrast, an example of low-risk exposure is senior citizens shopping in a market at an early hour designated for them. Respiratory protection similarly varies in effectiveness and cost, depending on the type of mask used. The effectiveness of respiratory protection ranges from homemade masks3 to surgical masks, N-95 respirators (that capture 95% of droplets), N-99s, powered-air purifying respirators used in biosafety level 3 laboratories, and, finally, the highest level of containment, the full-body, air-supplied positive-pressure suits that use an external air source and are used in biosafety level 4 laboratories. Similarly, intensity of social distancing may range from individual quarantine to quarantine in group or family settings.To elucidate the concepts of Rose applied to COVID-19, since actual data are not available, we imagined the following hypothetical scenario, illustrated in Figures 1, 2, and 3. We propose that a population of 5.5 million has 10 levels of exposure to SARS-CoV-2, and we can divide the entire population into 10 groups (Figure 1). The highest-level exposure group, Group 10, comprises healthcare workers involved in high-risk procedures and is the smallest group, which we set to 100,000. Each successive level of exposure adds an additional 100,000 members. The entire population is 5.5 million. Group 1, the largest group, is the lowest-risk group. If we assume that low levels of exposure correlate with infection levels, we can then assign an arbitrary risk of infection to the lowest of 1 per 100 population, as illustrated in Figure 2. As we move through the exposure levels from low to high, we can assume that each higher level of exposure adds an additional risk of 1 per 100 population, resulting in populations at risk of infection of 2 per 100, 3 per 100, and so on. As the numbers at risk in each level of exposure (Figure 1) is multiplied by the rate of infection in that exposure group (Figure 2), we can predict in Figure 3 the distribution of new infections across the 10 levels of exposure.Figure 1. Distribution of population by 10 levels of exposure (1 = low; 10 = high).Figure 2. Relative rate of infection by 10 levels of exposure.Figure 3. Distribution of new infections by 10 levels of exposure.In this simulation, half of the new infections are in the top half of exposure groups, which have the smallest number of people. But, what may be surprising to some, half of new infections are also found in the bottom half of categories of exposure, which have the largest number of people. The implications of this exercise are as follows: to protect individuals in the subpopulation at high risk, we should use of the most effective interventions; however, to prevent a large number of cases and starve the epidemic of new sources of infection, we should also reduce exposure to those at lower levels of exposure through methods such as social distancing, somewhat effective personal protective equipment, and other measures.References1. Rose G. Sick individuals, sick populations. Int J Epidemiol. 1985;14(1):32-38. Crossref, Medline, Google Scholar2. Gordis L. Epidemiology. 5th ed. Philadelphia, PA: Elsevier Saunders; 2014. Google Scholar3. Davies A, Thompson K-A, Giri K, Kafatos G, Walker J, Bennet A. (2013) Testing the efficacy of homemade masks: would they protect in an influenza pandemic? Disaster Med Public Health Prep. 2013;7(4):413-418. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited bySARS-CoV-2: An Empirical Investigation of Rose's Population-based Logic3 August 2021 | Epidemiology, Vol. 32, No. 6 Volume 18Issue 6Dec 2020 InformationCopyright 2020, Mary Ann Liebert, Inc., publishersTo cite this article:William Halperin, Michel A. Ibrahim, and Nancy Connell.Geoffrey Rose's Strategy of Prevention Applied to COVID-19.Health Security.Dec 2020.502-504.http://doi.org/10.1089/hs.2020.0037Published in Volume: 18 Issue 6: December 14, 2020Online Ahead of Print:September 22, 2020 TopicsCoronavirusesCOVID-19Disease management programs PDF download
Continuing rapid advances in science and technology both pose potential risks and offer potential benefits for the effective implementation of the Biological Weapons Convention (BWC). The lack of commonly accepted methods for assessing relevant risks and benefits present significant challenges to building common understandings that could support policy choices. This article argues that qualitative frameworks can provide the basis to structure BWC discussions about potential risks and benefits, reveal areas of agreement and disagreement, and provide a basis for continuing dialogue. It draws on the results of a workshop held in Geneva during the 2019 BWC Meetings of Experts. A diverse group of international experts were given the opportunity to apply 2 qualitative frameworks developed specifically to assess potential biosecurity concerns arising from emerging science and technology to BWC-relevant case examples. Participants discussed how such frameworks might be adapted and put into action to help support the BWC. They also began a discussion of how a comparable framework to assess potential benefits could be developed.
This report outlines a number of trends that are facilitating advances in different areas of the life sciences, including immunology, neuroscience, human genetics and reproductive science, agriculture and infectious disease. Research and development in these fields is overwhelmingly undertaken for peaceful purposes and potentially provides many benefits to society, the global economy, and future generations. However, the same areas of research raise a number of ethical, legal, safety and security concerns, including concerns that developments therein could feed into of new forms of biological weapons with different and potentially more damaging effects to those of the past.
We report the heterologous expression, structure, and antimicrobial activity of a lasso peptide, ubonodin, encoded in the genome of Burkholderia ubonensis . The topology of ubonodin is unprecedented amongst lasso peptides, with 18 of its 28 amino acids found in the mechanically bonded loop segment. Ubonodin inhibits RNA polymerase in vitro and has potent antimicrobial activity against several pathogenic members of the Burkholderia genus, most notably B. cepacia and B. multivorans , causative agents of lung infections in cystic fibrosis patients.
Enantiopure compounds with a strategically incorporated fluorine atom intended to enhance LpxC inhibition have been synthesized using an organocascade fluorination reaction as the key step. These are the first low molecular weight LpxC inhibitors to contain a fluorine atom on a critically important chiral center that is substituted with two pharmacophoric moieties, and were thusly designed to provide new SAR data for this class of compounds. Fluorinated compounds were evaluated against ESKAPE pathogens and exhibited MICs of ≤12.5 μg mL-1 against Pseudomonas aeruginosa.
Filamenting temperature sensitive protein Z (FtsZ) is an essential bacterial cell division protein and a promising target for the development of new antibacterial therapeutics.