Antibiotic-resistant Staphylococcus aureus remains a leading cause of antibiotic resistance-associated mortality in the United States. Given the reality of multi-drug resistant infections, it is imperative that we establish and maintain a pipeline of new compounds to replace or supplement our current antibiotics. A first step towards this goal is to prioritize targets by identifying the genes most consistently required for survival across the S. aureus phylogeny. Here we report the first direct comparison of multiple strains of S. aureus via transposon sequencing. We show that mutant fitness varies by strain in key pathways, underscoring the importance of using more than one strain to differentiate between core and strain-dependent essential genes. We treated the libraries with daptomycin to assess whether the strain-dependent differences impact pathways important for survival. Despite baseline differences in gene importance, several pathways, including the lipoteichoic acid pathway, consistently promote survival under daptomycin exposure, suggesting core vulnerabilities that can be exploited to resensitize daptomycin-nonsusceptible isolates. We also demonstrate the merit of using transposons with outward-facing promoters capable of overexpressing nearby genes for identifying clinically-relevant gain-of-function resistance mechanisms. Together, the daptomycin vulnerabilities and resistance mechanisms support a mode of action with wide-ranging effects on the cell envelope and cell division. This work adds to a growing body of literature demonstrating the nuanced insights gained by comparing Tn-Seq results across multiple bacterial strains.

The legend of the Figure currently reads: “A formula for advancing surgical system strengthening and World Health Assembly resolution 68.15 through the World Health Organization’s thirteenth General Programme of Work (GPW-13). This graphic depicts the three strategic shifts outlined in GPW-13 and ties them to specific avenues for surgical system strengthening to achieve overarching goals. GPW-13 = Thirteenth General Programme of Work; NSOAPs = National Surgical, Obstetric, and Anesthesia Plans; PHC = primary healthcare; SDG 3 = Sustainable Development Goal 3; UHC = universal health coverage; WHA 68.18 = World Health Assembly resolution 68.15. ” The corrected Figure legend should read: A formula for advancing surgical system strengthening and World Health Assembly resolution 68.15 through the World Health Organization’s thirteenth General Programme of Work (GPW-13). This graphic depicts the three strategic shifts outlined in GPW-13 and ties them to specific avenues for surgical system strengthening to achieve overarching goals. GPW-13 = Thirteenth General Programme of Work; NSOAPs = National Surgical, Obstetric, and Anesthesia Plans; PHC = primary healthcare; SDG 3 = Sustainable Development Goal 3; UHC = universal health coverage; WHA 68.15 = World Health Assembly resolution 68.15.

An excise tax of 1 peso per liter on sugar-sweetened beverages was implemented in Mexico in 2014. We estimated the cost-effectiveness of this tax and an alternative tax scenario of 2 pesos per liter. We developed a cohort simulation model calibrated for Mexico to project the impact of the tax over ten years. The current tax is projected to prevent 239,900 cases of obesity, 39 percent of which would be among children. It could also prevent 61,340 cases of diabetes, lead to gains of 55,300 quality-adjusted life-years, and avert 5,840 disability-adjusted life-years. The tax is estimated to save $3.98 per dollar spent on its implementation. Doubling the tax to 2 pesos per liter would nearly double the cost savings and health impact. Countries with comparable conditions could benefit from implementing a similar tax.

The sexually transmitted pathogen Neisseria gonorrhoeae is regarded as being on the way to becoming an untreatable superbug. Despite its clinical importance, little is known about its emergence and evolution, and how this corresponds with the introduction of antimicrobials. We present a genome-based phylogeographical analysis of 419 gonococcal isolates from across the globe. Results indicate that modern gonococci originated in Europe or Africa, possibly as late as the sixteenth century and subsequently disseminated globally. We provide evidence that the modern gonococcal population has been shaped by antimicrobial treatment of sexually transmitted infections as well as other infections, leading to the emergence of two major lineages with different evolutionary strategies. The well-described multidrug-resistant lineage is associated with high rates of homologous recombination and infection in high-risk sexual networks. A second, multisusceptible lineage is more associated with heterosexual networks, with potential implications for infection control.

In recent years, several large studies have assessed the costs of national infant immunization programs, and the results of these studies are used to support planning and budgeting in low- and middle-income countries. However, few studies have addressed the costs and cost-effectiveness of interventions to improve immunization coverage, despite this being a major focus of policy attention. Without this information, countries and international stakeholders have little objective evidence on the efficiency of competing interventions for improving coverage.

Eating disorders (EDs) are common psychiatric disorders associated with high mortality. However, data on ED disease dynamics and treatment coverage are sparse.

In low- and middle-income countries, multisite costing studies are increasingly used to estimate healthcare program costs. These studies have employed a variety of estimators to summarize sample data and make inferences about overall program costs.

Viral hepatitis is a leading cause of morbidity and mortality worldwide, but has long been neglected by national and international policymakers. Recent modelling studies suggest that investing in the global elimination of viral hepatitis is feasible and cost-effective. In 2016, all 194 member states of the World Health Organization endorsed the goal to eliminate viral hepatitis as a public health threat by 2030, but complex systemic and social realities hamper implementation efforts. This paper presents eight case studies from a diverse range of countries that have invested in responses to viral hepatitis and adopted innovative approaches to tackle their respective epidemics. Based on an investment framework developed to build a global investment case for the elimination of viral hepatitis by 2030, national activities and key enablers are highlighted that showcase the feasibility and impact of concerted hepatitis responses across a range of settings, with different levels of available resources and infrastructural development. These case studies demonstrate the utility of taking a multipronged, public health approach to: (a) evidence-gathering and planning; (b) implementation; and (c) integration of viral hepatitis services into the Agenda for Sustainable Development. They provide models for planning, investment and implementation strategies for other countries facing similar challenges and resource constraints.