Introduction: Human host immune response following infection with the new variant of A/H1N1 pandemic influenza virus (nvH1N1) is poorly understood. We utilize here systemic cytokine and antibody levels in evaluating differences in early immune response in both mild and severe patients infected with nvH1N1. Methods: We profiled 29 cytokines and chemokines and evaluated the haemagglutination inhibition activity as quantitative and qualitative measurements of host immune responses in serum obtained during the first five days after symptoms onset, in two cohorts of nvH1N1 infected patients. Severe patients required hospitalization (n = 20), due to respiratory insufficiency (10 of them were admitted to the intensive care unit), while mild patients had exclusively flu-like symptoms (n = 15). A group of healthy donors was included as control (n = 15). Differences in levels of mediators between groups were assessed by using the non parametric U-Mann Whitney test. Association between variables was determined by calculating the Spearman correlation coefficient. Viral load was performed in serum by using real-time PCR targeting the neuraminidase gene. Results: Increased levels of innate-immunity mediators (IP-10, MCP-1, MIP-1β), and the absence of anti-nvH1N1 antibodies, characterized the early response to nvH1N1 infection in both hospitalized and mild patients. High systemic levels of type-II interferon (IFN-γ) and also of a group of mediators involved in the development of T-helper 17 (IL-8, IL-9, IL-17, IL-6) and T-helper 1 (TNF-α, IL-15, IL-12p70) responses were exclusively found in hospitalized patients. IL-15, IL-12p70, IL-6 constituted a hallmark of critical illness in our study. A significant inverse association was found between IL-6, IL-8 and PaO2 in critical patients. Conclusions: While infection with the nvH1N1 induces a typical innate response in both mild and severe patients, severe disease with respiratory involvement is characterized by early secretion of Th17 and Th1 cytokines usually associated with cell mediated immunity but also commonly linked to the pathogenesis of autoimmune/inflammatory diseases. The exact role of Th1 and Th17 mediators in the evolution of nvH1N1 mild and severe disease merits further investigation as to the detrimental or beneficial role these cytokines play in severe illness.
The use of vaccines to prevent and control cholera is currently under debate. Shanchol is one of the two oral cholera vaccines prequalified by the World Health Organization; however, its effectiveness under field conditions and the protection it confers in the first months after administration remain unknown. The main objective of this study was to estimate the short-term effectiveness of two doses of Shanchol used as a part of the integrated response to a cholera outbreak in Africa.
Motivation: The progress of High Throughput Sequencing (HTS) technologies and the reduction in the sequencing costs are such that Whole Genome Sequencing (WGS) could replace many traditional laboratory assays and procedures. Exploiting the volume of data produced by HTS platforms requires substantial computing skills and this is the main bottleneck in the implementation of WGS as a routine laboratory technique. The way in which the vast amount of results are presented to researchers and clinicians with no specialist knowledge of genome sequencing is also a significant issue. Results: Here we present TORMES, a user-friendly pipeline for WGS analysis of bacteria from any origin generated by HTS on Illumina platforms. TORMES is designed for non-bioinformatician users, and automates the steps required for WGS analysis directly from the raw sequence data: sequence quality filtering, de novo assembly, draft genome ordering against a reference, genome annotation, multi-locus sequence typing (MLST), searching for antibiotic resistance and virulence genes, and pangenome comparisons. Once the analysis is finished, TORMES generates and interactive web-like report that can be opened in any web browser and shared and revised by researchers in a simple manner. TORMES can be run by using very simple commands and represent a quick an easy way to perform WGS analysis. Availability and implementation: TORMES is free available at https://github.com/nmquijada/tormes. Supplementary information: Supplementary data are available at Bioinformatics online.