Characteristics of Microbes Most Likely to Cause Pandemics and Global Catastrophes.

Predicting which pathogen will confer the highest global catastrophic biological risk (GCBR) of a pandemic is a difficult task. Many approaches are retrospective and premised on prior pandemics; however, such an approach may fail to appreciate novel threats that do not have exact historical precedent. In this paper, based on a study and project we undertook, a new paradigm for pandemic preparedness is presented. This paradigm seeks to root pandemic risk in actual attributes possessed by specific classes of microbial organisms and leads to specific recommendations to augment preparedness activities.

Clinical management of potential bioterrorism-related conditions.

The agents most likely to be used in bioterrorism attacks are reviewed, along with the clinical syndromes they produce and their treatment.

Challenges and Opportunities of Nontraditional Approaches to Treating Bacterial Infections.

Due to increasing rates of antimicrobial-resistant infections and the current inadequacy of the antibiotic pipeline, there is increasing interest in nontraditional approaches to antibacterial therapies. We define "traditional" agents as small-molecule agents that directly target bacterial components to exert a bacteriostatic or bactericidal effect, and "nontraditional approaches" as antimicrobial therapeutics that work through other means (ie, not a small molecule and/or utilizes a nontraditional target). Due to their atypical features, such therapies may be less susceptible to the emergence of resistance than traditional antibiotics. They include approaches such as monoclonal antibodies, virulence disruptors, immunomodulators, phage therapies, microbiome-based therapies, antibiotic potentiators, and antisense approaches. This article discusses both the developmental and regulatory advantages and challenges associated with each of these technologies. By identifying existing regulatory and developmental gaps, we hope to provide a sense of where focusing resources may provide the greatest impact on successful product development.

An evaluation of the impact of social and structural determinants of health on forgone care during the COVID-19 pandemic in Baltimore, Maryland.

Evidence suggests that reductions in healthcare utilization, including forgone care, during the COVID-19 pandemic may be contributing towards excess morbidity and mortality. The objective of this study was to describe individual and community-level correlates of forgone care during the COVID-19 pandemic. We conducted a cross-sectional, secondary data analysis of participants (n = 2,003) who reported needing healthcare in two population-representative surveys conducted in Baltimore, MD in 2021 and 2021-2022. Abstracted data included the experience of forgone care, socio-demographic data, comorbidities, financial strain, and community of residence. Participant's community of residence were linked with data acquired from the Baltimore Neighborhood Indicators Alliance relevant to healthcare access and utilization, including walkability and internet access, among others. The data were analyzed using weighted random effects logistic regression. Individual-level factors found to be associated with increased odds for forgone care included individuals age 35-49 (compared to 18-34), female sex, experiencing housing insecurity during the pandemic, and the presence of functional limitations and mental illness. Black/African American individuals were found to have reduced odds of forgone care, compared to any other race. No community-level factors were significant in the multilevel analyses. Moving forward, it will be critical that health systems identify ways to address any barriers to care that populations might be experiencing, such as the use of mobile health services or telemedicine platforms. Additionally, public health emergency preparedness planning efforts must account for the unique needs of communities during future crises, to ensure that their health needs can continue to be met. Finally, additional research is needed to better understand how healthcare access and utilization practices have changed during versus before the pandemic.

Assessment of serosurveys for H5N1.

BACKGROUND: It has been suggested that the true case-fatality rate of human H5N1 influenza infection is appreciably less than the figure of approximately 60% that is based on official World Health Organization (WHO)-confirmed case reports because asymptomatic cases may have been missed. A number of seroepidemiologic studies have been conducted in an attempt to identify such missed cases. METHODS: We conducted a comprehensive literature review of all English-language H5N1 human serology surveys with detailed attention to laboratory methodology used (including whether investigators used criteria set by the WHO to define positive cases), laboratory controls used, and the clades/genotypes involved. RESULTS: Twenty-nine studies were included in the analysis. Few reported using unexposed control groups and one-third did not apply WHO criteria. Of studies that used WHO criteria, only 4 found any seropositive results to clades/genotypes of H5N1 that are currently circulating. No studies reported seropositive results to the clade 2/genotype Z viruses that have spread throughout Eurasia and Africa. CONCLUSIONS: This review suggests that the frequency of positive H5 serology results is likely to be low; therefore, it is essential that future studies adhere to WHO criteria and include unexposed controls in their laboratory assays to limit the likelihood of false-positive results.

Engineered H5N1: a rare time for restraint in science.

Two scientific teams have recently engineered the H5N1 virus to make it readily transmissible between ferrets. Given that ferrets are considered the most reliable animal surrogate for human influenza infection, the newly engineered H5N1 strain is probably transmissible between humans as well. The potential consequences of an engineered human-transmissible H5N1 strain are stunning. Although seasonal flu infects as much as 20% of the world's population-more than 1 billion persons-each year, only a small fraction of those with seasonal flu dies, most often the oldest, youngest, and sickest. If the newly engineered strain were to escape the laboratory (either by design or by accident) and spread as widely as seasonal flu with anywhere near the current confirmed H5N1 human case-fatality rate, it could endanger the lives of hundreds of millions of persons. The possible benefits of this work do not justify taking such risks. As clinicians, we have a stake in this issue with our responsibilities for the diagnosis and treatment of influenza. We embrace the principle of free and open exchange of scientific information, but we also believe in the principle of "first, do no harm." These 2 principles have come into a moment of rare conflict. It seems most reasonable and prudent to request that the involved scientific community and its institutions exercise restraint by restricting dissemination of the experimental results and discontinuing work on the engineered H5N1 strains. If a highly compelling case is made for continued work on this strain despite the risks, the work should be controlled and should merit the greatest scrutiny.

Proposed Changes to U.S. Policy on Potential Pandemic Pathogen Oversight and Implementation.

We propose here changes to the U.S. government policy on potential pandemic pathogen (PPP) oversight and implementation, emphasizing transparency of the review process and the content of the review, publication of the review in advance, responsible publication of enhanced PPP research, high-level signoff on approvals of enhanced PPP experiments, and the need for a significant effort to establish a common international approach to enhanced PPP work. We advocate that the U.S. government recommend, and non-U.S. government funders and journals adopt, a set of best practices that would extend important considerations of biosafety and biosecurity to all work on enhanced potential pandemic pathogens regardless of funding source.

The biosecurity benefits of genetic engineering attribution.

Biology can be misused, and the risk of this causing widespread harm increases in step with the rapid march of technological progress. A key security challenge involves attribution: determining, in the wake of a human-caused biological event, who was responsible. Recent scientific developments have demonstrated a capability for detecting whether an organism involved in such an event has been genetically modified and, if modified, to infer from its genetic sequence its likely lab of origin. We believe this technique could be developed into powerful forensic tools to aid the attribution of outbreaks caused by genetically engineered pathogens, and thus protect against the potential misuse of synthetic biology.

The national disaster medical system: past, present, and suggestions for the future.

This article reviews the history and structure of the National Disaster Medical System (NDMS), with an emphasis on its definitive care component. NDMS's capacity to handle very large mass casualty events, such as those included in the National Planning Scenarios, is examined. Following Hurricane Katrina, Congress called for a reevaluation of NDMS. In that context, we make three key suggestions to improve NDMS's capacity to respond to large mass casualty disasters: (1) increase the level of engagement by the private (i.e., nonfederal) healthcare system in preparedness and response efforts; (2) increase the reliance on regional hospital collaborative networks as part of the backbone of the NDMS system; and (3) develop additional, alternative patient transportation systems, linked to the overall NDMS patient tracking effort, to decrease the sole reliance on DoD long-haul air transport in medical evacuation.

Regional approaches to hospital preparedness.

This article describes issues related to the engagement of hospitals and other community partners in a coordinated regional healthcare preparedness and response effort. The report is based on interviews with public health and hospital representatives from 13 regions or states across the country. It aims to identify key ingredients for building successful regional partnerships for healthcare preparedness as well as critical challenges and policy and practical recommendations for their development and sustainability.

Challenges to global surveillance and response to infectious disease outbreaks of international importance.

This article presents a notional scheme of global surveillance and response to infectious disease outbreaks and reviews 14 international surveillance and response programs. In combination, the scheme and the programs illustrate how, in an ideal world and in the real world, infectious disease outbreaks of public health significance could be detected and contained. Notable practices and achievements of the programs are cited; these may be useful when instituting new programs or redesigning existing ones. Insufficiencies are identified in four critical areas: health infrastructure; scientific methods and concepts of operation; essential human, technical, and financial resources; and international policies. These insufficiencies challenge global surveillance of and response to infectious disease outbreaks of international importance. This article is intended to help policymakers appreciate the complexity of the problem and assess the impact and cost-effectiveness of proposed solutions. An assessment of the potential contribution of appropriate diagnostic tests to surveillance and response is included.

Comments from the Center for Biosecurity of UPMC on proposed revisions to federal quarantine rules.

On November 30, 2005, the U.S. Centers for Disease Control and Prevention (CDC) proposed changes to federal quarantine regulations (42 CFR Parts 70 and 71). As stated in the proposed rules, the intent of changes is "to clarify and strengthen existing procedures to enable CDC to respond more effectively to current and potential communicable disease threats." Parts 70 and 71 of 42 CFR authorize the Secretary of the Department of Health and Human Services (HHS) to make and enforce regulations "as in his judgement are necessary to prevent the introduction, transmission, and spread of communicable diseases" from foreign countries (Part 71) and between states (Part 70). The Center for Biosecurity of UPMC reviewed the proposed revisions to the quarantine regulations and submitted to CDC the following analysis as its official comments on the revised rules.