The devastating Haitian cholera outbreak that began in October 2010 is the first known cholera epidemic in this island nation. Epidemiological and genomic data have provided strong evidence that United Nations security forces from Nepal introduced toxigenic Vibrio cholerae O1, the cause of epidemic cholera, to Haiti shortly before the outbreak arose. However, some have contended that indigenous V. cholerae contributed to the outbreak. In a recent paper (mBio 4:e00398-13, 2013), L. S. Katz et al. explored the nature and rate of changes in this ancient pathogen’s genome during an outbreak, based on whole-genome sequencing of 23 Haitian V. cholerae clinical isolates obtained over a 20-month period. Notably, they detected point mutations, deletions, and inversions but found no insertion of horizontally transmitted DNA, arguing strongly against the idea that autochthonous V. cholerae donated DNA to the outbreak strain. Furthermore, they found that Haitian epidemic V. cholerae isolates were virtually untransformable. Comparative genomic analyses revealed that the Haitian isolates were nearly identical to isolates from Nepal and that the Nepalese-Haitian isolates were distinguishable from isolates circulating elsewhere in the world. Reconstruction of the phylogeny of the Haitian isolates was consistent with a single introduction of V. cholerae to Haiti sometime between late July and late October 2010, dates remarkably concordant with epidemiological observations. In aggregate, this paper provides additional compelling evidence that the V. cholerae strain responsible for the Haitian cholera epidemic came from Nepal and illustrates the power of whole-genome-based analyses for epidemiology, pathogen evolution, and forensics.

Regulatory T cells (Tregs) that express the transcription factor Foxp3 are critical for regulating intestinal inflammation. Candidate microbe approaches have identified bacterial species and strain-specific molecules that can affect intestinal immune responses, including species that modulate Treg responses. Because neither all humans nor mice harbor the same bacterial strains, we posited that more prevalent factors exist that regulate the number and function of colonic Tregs. We determined that short-chain fatty acids, gut microbiota-derived bacterial fermentation products, regulate the size and function of the colonic Treg pool and protect against colitis in a Ffar2-dependent manner in mice. Our study reveals that a class of abundant microbial metabolites underlies adaptive immune microbiota coadaptation and promotes colonic homeostasis and health.

Several mitogens such as vascular endothelial growth factor (VEGF) have been implicated in mammalian vascular proliferation and repair. However, the molecular mediators of human blood-nerve barrier (BNB) development and specialization are unknown. Primary human endoneurial endothelial cells (pHEndECs) were expanded in vitro and specific mitogen receptors detected by western blot. pHEndECs were cultured with basal medium containing different mitogen concentrations with or without heparin. Non-radioactive cell proliferation, Matrigel(™)-induced angiogenesis and sterile micropipette injury wound healing assays were performed. Proliferation rates, number and total length of induced microvessels, and rate of endothelial cell monolayer wound healing were determined and compared to basal conditions. VEGF-A165 in the presence of heparin, was the most potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. 1.31 nM VEGF-A165 induced ~110 % increase in cell proliferation relative to basal conditions (∼51 % without heparin). 2.62 pM VEGF-A165 induced a three-fold increase in mean number of microvessels and 3.9-fold increase in total capillary length/field relative to basal conditions. In addition, 0.26 nM VEGF-A165 induced ∼1.3-fold increased average rate of endothelial wound healing 4-18 h after endothelial monolayer injury, mediated by increased cell migration. VEGF-A165 was the only mitogen capable of complete wound closure, occurring within 30 h following injury via increased cell proliferation. This study demonstrates that VEGF-A165, in the presence of heparin, is a potent inducer of pHEndEC proliferation, angiogenesis, and wound healing in vitro. VEGF-A165 may be an important mitogen necessary for human BNB development and recovery in response to peripheral nerve injury.

Millions of dollars are invested annually under the umbrella of national health systems strengthening. Global health initiatives provide funding for low- and middle-income countries through disease-oriented programmes while maintaining that the interventions simultaneously strengthen systems. However, it is as yet unclear which, and to what extent, system-level interventions are being funded by these initiatives, nor is it clear how much funding they allocate to disease-specific activities – through conventional ‘vertical-programming’ approach. Such funding can be channelled to one or more of the health system building blocks while targeting disease(s) or explicitly to system-wide activities.

Turkey has successfully introduced health system changes and provided its citizens with the right to health to achieve universal health coverage, which helped to address inequities in financing, health service access, and health outcomes. We trace the trajectory of health system reforms in Turkey, with a particular emphasis on 2003-13, which coincides with the Health Transformation Program (HTP). The HTP rapidly expanded health insurance coverage and access to health-care services for all citizens, especially the poorest population groups, to achieve universal health coverage. We analyse the contextual drivers that shaped the transformations in the health system, explore the design and implementation of the HTP, identify the factors that enabled its success, and investigate its effects. Our findings suggest that the HTP was instrumental in achieving universal health coverage to enhance equity substantially, and led to quantifiable and beneficial effects on all health system goals, with an improved level and distribution of health, greater fairness in financing with better financial protection, and notably increased user satisfaction. After the HTP, five health insurance schemes were consolidated to create a unified General Health Insurance scheme with harmonised and expanded benefits. Insurance coverage for the poorest population groups in Turkey increased from 2·4 million people in 2003, to 10·2 million in 2011. Health service access increased across the country-in particular, access and use of key maternal and child health services improved to help to greatly reduce the maternal mortality ratio, and under-5, infant, and neonatal mortality, especially in socioeconomically disadvantaged groups. Several factors helped to achieve universal health coverage and improve outcomes. These factors include economic growth, political stability, a comprehensive transformation strategy led by a transformation team, rapid policy translation, flexible implementation with continuous learning, and simultaneous improvements in the health system, on both the demand side (increased health insurance coverage, expanded benefits, and reduced cost-sharing) and the supply side (expansion of infrastructure, health human resources, and health services).