An Analysis of International Health Regulations Emergency Committees and Public Health Emergency of International Concern Designations

Nine public health events have been assessed for the potential declaration of a Public Health Emergency of International Concern (PHEIC). According to the World Health Organization (WHO) International Health Regulations (IHR), a PHEIC is defined as an extraordinary event that constitutes a public health risk to other states through international spread and requires a coordinated international response. The WHO Director-General convenes Emergency Committees (ECs) to provide their advice on whether an event constitutes a PHEIC. The EC rationales have been continuously criticised for being non-transparent and contradictory to the IHR. This first comprehensive analysis of EC rationale provides recommendations to increase clarity of EC decisions which will strengthen the IHR and WHO’s legitimacy in future outbreaks. A total of 66 EC statements were reviewed from the nine public health outbreaks of influenza A, Middle East respiratory syndrome coronavirus, polio, Ebola virus disease, Zika, yellow fever and coronavirus disease-2019 (COVID-19). Statements were analysed to determine which of the three IHR criteria were noted as contributing towards the EC’s justification on whether to recommend to the WHO Director-General that a PHEIC be declared and what language was used to explain their decision. Interpretation of the criteria were often vague and applied inconsistently. ECs often failed to describe and justify which criteria had been satisfied. Guidelines must be developed for the standardised interpretation of IHR core criteria. The ECs must clearly identify and justify which criteria have contributed to their rationale for or against PHEIC declaration. Striving for more consistency and transparency in EC justifications would benefit future deliberations and provide more understanding and support for the process

The Value Proposition of the Global Health Security Index

Infectious disease outbreaks pose major threats to human health and security. Countries with robust capacities for preventing, detecting and responding to outbreaks can avert many of the social, political, economic and health system costs of such crises. The Global Health Security Index (GHS Index)—the first comprehensive assessment and benchmarking of health security and related capabilities across 195 countries—recently found that no country is sufficiently prepared for epidemics or pandemics. The GHS Index can help health security stakeholders identify areas of weakness, as well as opportunities to collaborate across sectors, collectively strengthen health systems and achieve shared public health goals. Some scholars have recently offered constructive critiques of the GHS Index’s approach to scoring and ranking countries; its weighting of select indicators; its emphasis on transparency; its focus on biosecurity and biosafety capacities; and divergence between select country scores and corresponding COVID-19-associated caseloads, morbidity, and mortality. Here, we (1) describe the practical value of the GHS Index; (2) present potential use cases to help policymakers and practitioners maximise the utility of the tool; (3) discuss the importance of scoring and ranking; (4) describe the robust methodology underpinning country scores and ranks; (5) highlight the GHS Index’s emphasis on transparency and (6) articulate caveats for users wishing to use GHS Index data in health security research, policymaking and practice

Redox proteomics of the inflammatory secretome identifies a common set of redoxins and other glutathionylated proteins released in inflammation, influenza virus infection and oxidative stress

Protein cysteines can form transient disulfides with glutathione (GSH), resulting in the production of glutathionylated proteins, and this process is regarded as a mechanism by which the redox state of the cell can regulate protein function. Most studies on redox regulation of immunity have focused on intracellular proteins. In this study we have used redox proteomics to identify those proteins released in glutathionylated form by macrophages stimulated with lipopolysaccharide (LPS) after pre-loading the cells with biotinylated GSH. Of the several proteins identified in the redox secretome, we have selected a number for validation. Proteomic analysis indicated that LPS stimulated the release of peroxiredoxin (PRDX) 1, PRDX2, vimentin (VIM), profilin1 (PFN1) and thioredoxin 1 (TXN1). For PRDX1 and TXN1, we were able to confirm that the released protein is glutathionylated. PRDX1, PRDX2 and TXN1 were also released by the human pulmonary epithelial cell line, A549, infected with influenza virus. The release of the proteins identified was inhibited by the anti-inflammatory glucocorticoid, dexamethasone (DEX), which also inhibited tumor necrosis factor (TNF)-α release, and by thiol antioxidants (N-butanoyl GSH derivative, GSH-C4, and N-acetylcysteine (NAC), which did not affect TNF-α production. The proteins identified could be useful as biomarkers of oxidative stress associated with inflammation, and further studies will be required to investigate if the extracellular forms of these proteins has immunoregulatory functions

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements