Open data for COVID-19 policy analysis and mapping.

As the COVID-19 pandemic unfolded in the spring of 2020, governments around the world began to implement policies to mitigate and manage the outbreak. Significant research efforts were deployed to track and analyse these policies in real-time to better inform the response. While much of the policy analysis focused narrowly on social distancing measures designed to slow the spread of disease, here, we present a dataset focused on capturing the breadth of policy types implemented by jurisdictions globally across the whole-of-government. COVID Analysis and Mapping of Policies (COVID AMP) includes nearly 50,000 policy measures from 150 countries, 124 intermediate areas, and 235 local areas between January 2020 and June 2022. With up to 40 structured and unstructured characteristics encoded per policy, as well as the original source and policy text, this dataset provides a uniquely broad capture of the governance strategies for pandemic response, serving as a critical data source for future work in legal epidemiology and political science.

The World Health Organization's Disease Outbreak News: A retrospective database.

The World Health Organization (WHO) notifies the global community about disease outbreaks through the Disease Outbreak News (DON). These online reports tell important stories about both outbreaks themselves and the high-level decision making that governs information sharing during public health emergencies. However, they have been used only minimally in global health scholarship to date. Here, we collate all 2,789 of these reports from their first use through the start of the Covid-19 pandemic (January 1996 to December 2019), and develop an annotated database of the subjective and often inconsistent information they contain. We find that these reports are dominated by a mix of persistent worldwide threats (particularly influenza and cholera) and persistent epidemics (like Ebola virus disease in Africa or MERS-CoV in the Middle East), but also document important periods in history like the anthrax bioterrorist attacks at the turn of the century, the spread of chikungunya and Zika virus to the Americas, or even recent lapses in progress towards polio elimination. We present three simple vignettes that show how researchers can use these data to answer both qualitative and quantitative questions about global outbreak dynamics and public health response. However, we also find that the retrospective value of these reports is visibly limited by inconsistent reporting (e.g., of disease names, case totals, mortality, and actions taken to curtail spread). We conclude that sharing a transparent rubric for which outbreaks are considered reportable, and adopting more standardized formats for sharing epidemiological metadata, might help make the DON more useful to researchers and policymakers.

Emergency Department and Intensive Care Unit Overcrowding and Ventilator Shortages in US Hospitals During the COVID-19 Pandemic, 2020-2021.

OBJECTIVE: In 2020, the COVID-19 pandemic overburdened the US health care system because of extended and unprecedented patient surges and supply shortages in hospitals. We investigated the extent to which several US hospitals experienced emergency department (ED) and intensive care unit (ICU) overcrowding and ventilator shortages during the COVID-19 pandemic. METHODS: We analyzed Health Pulse data to assess the extent to which US hospitals reported alerts when experiencing ED overcrowding, ICU overcrowding, and ventilator shortages from March 7, 2020, through April 30, 2021. RESULTS: Of 625 participating hospitals in 29 states, 393 (63%) reported at least 1 hospital alert during the study period: 246 (63%) reported ED overcrowding, 239 (61%) reported ICU overcrowding, and 48 (12%) reported ventilator shortages. The number of alerts for overcrowding in EDs and ICUs increased as the number of COVID-19 cases surged. CONCLUSIONS: Timely assessment and communication about critical factors such as ED and ICU overcrowding and ventilator shortages during public health emergencies can guide public health response efforts in supporting federal, state, and local public health agencies.

Fifteen days in December: capture and analysis of Omicron-related travel restrictions.

Following the identification of the Omicron variant of the SARS-CoV-2 virus in late November 2021, governments worldwide took actions intended to minimise the impact of the new variant within their borders. Despite guidance from the WHO advising a risk-based approach, many rapidly implemented stringent policies focused on travel restrictions. In this paper, we capture 221 national-level travel policies issued during the 3 weeks following publicisation of the Omicron variant. We characterise policies based on whether they target travellers from specific countries or focus more broadly on enhanced screening, and explore differences in approaches at the regional level. We find that initial reactions almost universally focused on entry bans and flight suspensions from Southern Africa, and that policies continued to target travel from these countries even after community transmission of the Omicron variant was detected elsewhere in the world. While layered testing and quarantine requirements were implemented by some countries later in this 3-week period, these enhanced screening policies were rarely the first response. The timing and conditionality of quarantine and testing requirements were not coordinated between countries or regions, creating logistical complications and burdening travellers with costs. Overall, response measures were rarely tied to specific criteria or adapted to match the unique epidemiology of the new variant.

Investing in global health security: Estimating cost requirements for country-level capacity building.

The COVID-19 pandemic has highlighted critical gaps in global capacity to prevent, detect, and respond to infectious diseases. To effectively allocate investments that address these gaps, it is first necessary to quantify the extent of the need, evaluate the types of resources and activities that require additional support, and engage the global community in ongoing assessment, planning, and implementation. Which investments are needed, where, to strengthen health security? This work aims to estimate costs to strengthen country-level health security, globally and identify associated cost drivers. The cost of building public health capacity is estimated based on investments needed, per country, to progress towards the benchmarks identified by the World Health Organization's Joint External Evaluation (JEE). For each country, costs are estimated to progress to a score of "demonstrated capacity" (4) across indicators. Over five years, an estimated US$124 billion is needed to reach "demonstrated capacity" on each indicator of the JEE for each of the 196 States Parties to the International Health Regulations (IHR). Personnel costs, including skilled health, public health, and animal health workers, are the single most influential cost driver, comprising 66% of total costs. These findings, and the data generated by this effort, provide cost estimates to inform ongoing health security financing discussions at the global level. The results highlight the significant need for sustainable financing mechanisms for both workforce development and ongoing support for the health and public health workforce.

Law, criminalisation and HIV in the world: have countries that criminalise achieved more or less successful pandemic response?

How do choices in criminal law and rights protections affect disease-fighting efforts? This long-standing question facing governments around the world is acute in the context of pandemics like HIV and COVID-19. The Global AIDS Strategy of the last 5 years sought to prevent mortality and HIV transmission in part through ensuring people living with HIV (PLHIV) knew their HIV status and could suppress the HIV virus through antiretroviral treatment. This article presents a cross-national ecological analysis of the relative success of national AIDS responses under this strategy, where laws were characterised by more or less criminalisation and with varying rights protections. In countries where same-sex sexual acts were criminalised, the portion of PLHIV who knew their HIV status was 11% lower and viral suppression levels 8% lower. Sex work criminalisation was associated with 10% lower knowledge of status and 6% lower viral suppression. Drug use criminalisation was associated with 14% lower levels of both. Criminalising all three of these areas was associated with approximately 18%-24% worse outcomes. Meanwhile, national laws on non-discrimination, independent human rights institutions and gender-based violence were associated with significantly higher knowledge of HIV status and higher viral suppression among PLHIV. Since most countries did not achieve 2020 HIV goals, this ecological evidence suggests that law reform may be an important tool in speeding momentum to halt the pandemic.

Understanding and comparing HIV-related law and policy environments: cross-national data and accountability for the global AIDS response.

Law and policy differences help explain why, as HIV-related science has advanced swiftly, some countries have realised remarkable progress on AIDS while others see expanding epidemics. We describe the structure and findings of a new dataset and research platform, the HIV Policy Lab, which fills an important knowledge gap by measuring the HIV-related policy environment across 33 indicators and 194 countries over time, with online access and visualisation. Cross-national indicators can be critical tools in international governance-building social power to monitor state behaviour with the potential to change policy and improve domestic accountability. This new and evolving effort collects data about policy through review of legal documents, official government reports and systematic review of secondary sources. Alignment between national policy environments and global norms is demonstrated through comparison with international public health guidance and agreements. We demonstrate substantial variation in the content of law and policies between countries, regions and policy areas. Given progress in basic and implementation science, it would be tempting to believe most countries have adopted policies aligned with global norms, with a few outliers. Data show this is not the case. Globally, alignment is higher on clinical and treatment policies than on prevention, testing and structural policies. Policy-makers, researchers, civil society, finance agencies and others can use these data to better understand the policy environment within and across countries and support reform. Longitudinal analysis enables evaluation of the impact of laws and policies on HIV outcomes and research about the political drivers of policy choice.

CDC's Flu on Call Simulation: Testing a National Helpline for Use During an Influenza Pandemic.

During an influenza pandemic, healthcare facilities are likely to be filled to capacity, leading to delays in seeing a provider and obtaining treatment. Flu on Call is a collaborative effort between the US Centers for Disease Control and Prevention and partners to develop a toll-free telephone helpline to reduce the burden on healthcare facilities and improve access to antivirals for people who are ill during an influenza pandemic. This study tested the feasibility of Flu on Call during a 1-day simulation using a severe pandemic scenario. Trained volunteer actors placed calls to the helpline using prepared scripts that were precoded for an expected outcome ("disposition") of the call. Scripts represented callers who were ill, those calling for someone else who was ill, and callers who were only seeking information. Information specialists and medical professionals managed the calls. Results demonstrated that Flu on Call may effectively assist callers during a pandemic, increase access to antiviral prescriptions, and direct patients to the appropriate level of care. Overall, 84% of calls exactly matched the expected call disposition; few calls (2%) were undermanaged (eg, the caller was ill but not transferred to a medical professional or received advice from the medical professional that was less intensive than what was warranted). Callers indicated a high level of satisfaction (83% reported their needs were met). Because of the high volume of calls that may be received during a severe pandemic, the Flu on Call platform should evolve to include additional triage channels (eg, through internet, chat, and/or text access).

Tracking the Flow of Funds in Global Health Security.

Countries, philanthropies, and private sector organizations have been actively investing in global health security around the world. However, despite the coordinated approach to funding within the Global Health Security Agenda, there is currently no well-established method to track the commitment and disbursal of funds for global health security from funders to recipients or to identify the activities supported by existing funding initiatives. To address this need, we developed the Global Health Security Tracking Dashboard. This interactive, publicly available, Web-based dashboard maps the flow of funds from funder to recipient and categorizes the target efforts of those funds, allowing users to identify patterns of influence and success in health security funding implementation. The dashboard provides an evidence-based approach for defining targets for future funding by identifying the areas in which funds have not yet been effectively allocated, showcasing successes, and providing a source of information to promote mutual accountability.

Basal constriction during midbrain-hindbrain boundary morphogenesis is mediated by Wnt5b and focal adhesion kinase.

Basal constriction occurs at the zebrafish midbrain-hindbrain boundary constriction (MHBC) and is likely a widespread morphogenetic mechanism. 3D reconstruction demonstrates that MHBC cells are wedge-shaped, and initially constrict basally, with subsequent apical expansion. wnt5b is expressed in the MHB and is required for basal constriction. Consistent with a requirement for this pathway, expression of dominant negative Gsk3ß overcomes wnt5b knockdown. Immunostaining identifies focal adhesion kinase (Fak) as active in the MHB region, and knockdown demonstrates Fak is a regulator of basal constriction. Tissue specific knockdown further indicates that Fak functions cell autonomously within the MHBC. Fak acts downstream of wnt5b, suggesting that Wnt5b signals locally as an early step in basal constriction and acts together with more widespread Fak activation. This study delineates signaling pathways that regulate basal constriction during brain morphogenesis.

Strengthening health security: an intuitive and user-friendly tool to estimate country-level costs.

Member States of the WHO working to build capacity under the International Health Regulations (IHR) are advised to develop prioritised, costed plans to implement improvements based on the results of voluntary external assessments. Defining the costs associated with capacity building under the IHR, however, has challenged nations, funders and supporting organisations. Most current efforts to develop costed national action plans involve long-term engagements that may take weeks or months to complete. While these efforts have value in and of themselves, there is an urgent need for a rapid-use tool to provide cost estimates regardless of the level of expertise of the personnel assigned to the task. In this paper, we describe a tool that can-in a matter of hours-provide country-level cost estimates for capacity building under the IHR. This paper also describes how the tool can be used in countries, as well as the challenges inherent in any costing process.

Decision support for evidence-based integration of disease control: A proof of concept for malaria and schistosomiasis.

AUTHOR SUMMARY: Designing and implementing effective programs for infectious disease control requires complex decision-making, informed by an understanding of the diseases, the types of disease interventions and control measures available, and the disease-relevant characteristics of the local community. Though disease modeling frameworks have been developed to address these questions and support decision-making, the complexity of current models presents a significant barrier to on-the-ground end users. The picture is further complicated when considering approaches for integration of different disease control programs, where co-infection dynamics, treatment interactions, and other variables must also be taken into account. Here, we describe the development of an application available on the internet with a simple user interface, to support on-the-ground decision-making for integrating disease control, given local conditions and practical constraints. The model upon which the tool is built provides predictive analysis for the effectiveness of integration of schistosomiasis and malaria control, two diseases with extensive geographical and epidemiological overlap. This proof-of-concept method and tool demonstrate significant progress in effectively translating the best available scientific models to support pragmatic decision-making on the ground, with the potential to significantly increase the impact and cost-effectiveness of disease control.

Mapping stakeholders and policies in response to deliberate biological events.

BACKGROUND: Recent infectious disease outbreaks have brought increased attention to the need to strengthen global capacity to prevent, detect, and respond to natural biological threats. However, deliberate biological events also represent a significant global threat, but have received relatively little attention. While the Biological Weapons Convention provides a foundation for the response to deliberate biological events, the political mechanisms to respond to and recover from such an event are poorly defined. METHODS: We performed an analysis of the epidemiological timeline, the international policies triggered as a notional deliberate biological event unfolds, and the corresponding stakeholders and mandates assigned by each policy. FINDINGS: The results of this analysis identify a significant gap in both policy and stakeholder mandates: there is no single policy nor stakeholder mandate for leading and coordinating response activities associated with a deliberate biological event. These results were visualized using an open source web-based tool published at https://dbe.talusanalytics.com. INTERPRETATION: While there are organizations and stakeholders responsible for leading security or public health response, these roles are non-overlapping and are led by organizations not with limited interaction outside such events. The lack of mandates highlights a gap in the mechanisms available to coordinate response and a gap in guidance for managing the response. The results of the analysis corroborate anecdotal evidence from stakeholder meetings and highlight a critical need and gap in deliberate biological response policy.

Public health and medical preparedness for a nuclear detonation: the nuclear incident medical enterprise.

Resilience and the ability to mitigate the consequences of a nuclear incident are enhanced by (1) effective planning, preparation and training; (2) ongoing interaction, formal exercises, and evaluation among the sectors involved; (3) effective and timely response and communication; and (4) continuous improvements based on new science, technology, experience, and ideas. Public health and medical planning require a complex, multi-faceted systematic approach involving federal, state, local, tribal, and territorial governments; private sector organizations; academia; industry; international partners; and individual experts and volunteers. The approach developed by the U.S. Department of Health and Human Services Nuclear Incident Medical Enterprise (NIME) is the result of efforts from government and nongovernment experts. It is a "bottom-up" systematic approach built on the available and emerging science that considers physical infrastructure damage, the spectrum of injuries, a scarce resources setting, the need for decision making in the face of a rapidly evolving situation with limited information early on, timely communication, and the need for tools and just-in-time information for responders who will likely be unfamiliar with radiation medicine and uncertain and overwhelmed in the face of the large number of casualties and the presence of radioactivity. The components of NIME can be used to support planning for, response to, and recovery from the effects of a nuclear incident. Recognizing that it is a continuous work-in-progress, the current status of the public health and medical preparedness and response for a nuclear incident is provided.

Modeling the Effect of Herd Immunity and Contagiousness in Mitigating a Smallpox Outbreak.

The smallpox antiviral tecovirimat has recently been purchased by the U.S. Strategic National Stockpile. Given significant uncertainty regarding both the contagiousness of smallpox in a contemporary outbreak and the efficiency of a mass vaccination campaign, vaccine prophylaxis alone may be unable to control a smallpox outbreak following a bioterror attack. Here, we present the results of a compartmental epidemiological model that identifies conditions under which tecovirimat is required to curtail the epidemic by exploring how the interaction between contagiousness and prophylaxis coverage of the affected population affects the ability of the public health response to control a large-scale smallpox outbreak. Each parameter value in the model is based on published empirical data. We describe contagiousness parametrically using a novel method of distributing an assumed R-value over the disease course based on the relative rates of daily viral shedding from human and animal studies of cognate orthopoxvirus infections. Our results suggest that vaccination prophylaxis is sufficient to control the outbreak when caused either by a minimally contagious virus or when a very high percentage of the population receives prophylaxis. As vaccination coverage of the affected population decreases below 70%, vaccine prophylaxis alone is progressively less capable of controlling outbreaks, even those caused by a less contagious virus (R0 less than 4). In these scenarios, tecovirimat treatment is required to control the outbreak (total number of cases under an order of magnitude more than the number of initial infections). The first study to determine the relative importance of smallpox prophylaxis and treatment under a range of highly uncertain epidemiological parameters, this work provides public health decision-makers with an evidence-based guide for responding to a large-scale smallpox outbreak.

Live imaging of the zebrafish embryonic brain by confocal microscopy.

In this video, we demonstrate the method our lab has developed to analyze the cell shape changes and rearrangements required to bend and fold the developing zebrafish brain (Gutzman et al, 2008). Such analysis affords a new understanding of the underlying cell biology required for development of the 3D structure of the vertebrate brain, and significantly increases our ability to study neural tube morphogenesis. The embryonic zebrafish brain is shaped beginning at 18 hours post fertilization (hpf) as the ventricles within the neuroepithelium inflate. By 24 hpf, the initial steps of neural tube morphogenesis are complete. Using the method described here, embryos at the one cell stage are injected with mRNA encoding membrane-targeted green fluorescent protein (memGFP). After injection and incubation, the embryo, now between 18 and 24 hpf, is mounted, inverted, in agarose and imaged by confocal microscopy. Notably, the zebrafish embryo is transparent making it an ideal system for fluorescent imaging. While our analyses have focused on the midbrain-hindbrain boundary and the hindbrain, this method could be extended for analysis of any region in the zebrafish to a depth of 80-100 microm.