Estimating the impact of city-wide Aedes aegypti population control: An observational study in Iquitos, Peru.

During the last 50 years, the geographic range of the mosquito Aedes aegypti has increased dramatically, in parallel with a sharp increase in the disease burden from the viruses it transmits, including Zika, chikungunya, and dengue. There is a growing consensus that vector control is essential to prevent Aedes-borne diseases, even as effective vaccines become available. What remains unclear is how effective vector control is across broad operational scales because the data and the analytical tools necessary to isolate the effect of vector-oriented interventions have not been available. We developed a statistical framework to model Ae. aegypti abundance over space and time and applied it to explore the impact of citywide vector control conducted by the Ministry of Health (MoH) in Iquitos, Peru, over a 12-year period. Citywide interventions involved multiple rounds of intradomicile insecticide space spray over large portions of urban Iquitos (up to 40% of all residences) in response to dengue outbreaks. Our model captured significant levels of spatial, temporal, and spatio-temporal variation in Ae. aegypti abundance within and between years and across the city. We estimated the shape of the relationship between the coverage of neighborhood-level vector control and reductions in female Ae. aegypti abundance; i.e., the dose-response curve. The dose-response curve, with its associated uncertainties, can be used to gauge the necessary spraying effort required to achieve a desired effect and is a critical tool currently absent from vector control programs. We found that with complete neighborhood coverage MoH intra-domicile space spray would decrease Ae. aegypti abundance on average by 67% in the treated neighborhood. Our framework can be directly translated to other interventions in other locations with geolocated mosquito abundance data. Results from our analysis can be used to inform future vector-control applications in Ae. aegypti endemic areas globally

Micro-RNA-155 inhibits IFN-γ signaling in CD4+ T cells

Micro-RNA (miR) are increasingly recognized as critical regulators of tissue-specific patterns of gene expression. CD4+ T cells lacking miR-155, for example, exhibit bias towards Th2 differentiation, indicating that the absence of individual miR could alter CD4+ T cell differentiation. We now show that MiR-155 is induced upon T cell activation and that it promotes Th1 differentiation when over-expressed in activated CD4+ T cells. Antagonism of miR-155 leads to induction of IFN-γRα, and a functional miR-155 target site is identified within the 3′ UTR of IFN-γRα. These results identify IFN-γRα as a second miR-155 target in T cells and suggest that miR-155 contributes to Th1 differentiation in CD4+ T cells by inhibiting IFN-γ signaling

Induction of Cytotoxic T Lymphocyte Antigen 4 (Ctla-4) Restricts Clonal Expansion of Helper T Cells

Cytotoxic T lymphocyte antigen (CTLA)-4 plays an essential role in immunologic homeostasis. How this negative regulator of T cell activation executes its functions has remained controversial. We now provide evidence that CTLA-4 mediates a cell-intrinsic counterbalance to restrict the clonal expansion of proliferating CD4+ T cells. The regulation of CTLA-4 expression and function ensures that, after ∼3 cell divisions of expansion, most progeny will succumb to either proliferative arrest or death over the ensuing three cell divisions. The quantitative precision of the counterbalance hinges on the graded, time-independent induction of CTLA-4 expression during the first three cell divisions. In contrast to the limits imposed on unpolarized cells, T helper type 1 (Th1) and Th2 effector progeny may be rescued from proliferative arrest by interleukin (IL)-12 and IL-4 signaling, respectively, allowing appropriately stimulated progeny to proceed to the stage of tissue homing. These results suggest that the cell-autonomous regulation of CTLA-4 induction may be a central checkpoint of clonal expansion of CD4+ T cells, allowing temporally and spatially restricted growth of progeny to be dictated by the nature of the threat posed to the host

Requirement for T-bet in the aberrant differentiation of unhelped memory CD8+ T cells

Immunity to intracellular pathogens requires dynamic balance between terminal differentiation of short-lived, cytotoxic effector CD8+ T cells and self-renewal of central–memory CD8+ T cells. We now show that T-bet represses transcription of IL-7Rα and drives differentiation of effector and effector–memory CD8+ T cells at the expense of central–memory cells. We also found T-bet to be overexpressed in CD8+ T cells that differentiated in the absence of CD4+ T cell help, a condition that is associated with defective central–memory formation. Finally, deletion of T-bet corrected the abnormal phenotypic and functional properties of “unhelped” memory CD8+ T cells. T-bet, thus, appears to function as a molecular switch between central– and effector–memory cell differentiation. Antagonism of T-bet may, therefore, represent a novel strategy to offset dysfunctional programming of memory CD8+ T cells

Assessment of a Districtwide Policy on Availability of Competitive Beverages in Boston Public Schools, Massachusetts, 2013

Introduction: Competitive beverages are drinks sold outside of the federally reimbursable school meals program and include beverages sold in vending machines, a la carte lines, school stores, and snack bars. Competitive beverages include sugar-sweetened beverages, which are associated with overweight and obesity. We described competitive beverage availability 9 years after the introduction in 2004 of district-wide nutrition standards for competitive beverages sold in Boston Public Schools. Methods: In 2013, we documented types of competitive beverages sold in 115 schools. We collected nutrient data to determine compliance with the standards. We evaluated the extent to which schools met the competitive-beverage standards and calculated the percentage of students who had access to beverages that met or did not meet the standards. Results: Of 115 schools, 89.6% met the competitive beverage nutrition standards; 88.5% of elementary schools and 61.5% of middle schools did not sell competitive beverages. Nutrition standards were met in 79.2% of high schools; 37.5% did not sell any competitive beverages, and 41.7% sold only beverages meeting the standards. Overall, 85.5% of students attended schools meeting the standards. Only 4.0% of students had access to sugar-sweetened beverages. Conclusion: A comprehensive, district-wide competitive beverage policy with implementation support can translate into a sustained healthful environment in public schools