To the Editor: Killed oral cholera vaccines (OCVs) are part of the standard response package to a cholera outbreak, although the two-dose regimen of vaccines that has been prequalified by the World Health Organization (WHO) poses challenges to timely and efficient reactive vaccination campaigns. 1 Recent data suggest that the first dose alone provides short-term protection, similar to that of two doses, which may largely dictate the effect of OCVs during epidemics. [2][3][4] A cholera outbreak was detected in Lusaka, Zambia, in February 2016, after a period of 4 years without a reported case of cholera. An emergency reactive vaccination campaign was implemented in April 2016, targeting more than 500,000 persons who were at high risk for cholera in Lusaka (population, >2 million persons). The Ministry of Health, with support from Médecins sans Frontières and the WHO, decided to implement a single-dose campaign to quell the epidemic rapidly, in view of the insufficient number of vaccine doses that were available in the global stockpile to complete a two-dose campaign. In December 2016, when more doses became available, a second round of vaccination was organized and the second vaccine dose was offered to persons at risk.We conducted a matched case-control study to quantify the short-term effectiveness of a single-dose OCV regimen (Shanchol) between April 25, 2016, and June 15, 2016. The study was approved by two institutional review boards, and written informed consent was obtained from all the participants (see the Supplementary Appendix, available with the full text of this letter at NEJM.org). Cases of cholera were confirmed by means of culture, polymerase-chain-reaction as-

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.

BackgroundThe use of novel sepsis biomarkers has increased in recent years. However, their prognostic value with respect to illness severity has not been explored. In this work, we examined the ability of mid-regional proadrenomedullin (MR-proADM) in predicting mortality in sepsis patients with different degrees of organ failure, compared to that of procalcitonin, C-reactive protein and lactate.MethodsThis was a two-centre prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to the ICU. Plasma biomarkers were measured during the first 12 h of admission. The association between biomarkers and 28-day mortality was assessed by Cox regression analysis and Kaplan–Meier curves. Patients were divided into three groups as evaluated by the Sequential Organ Failure Assessment (SOFA) score. The accuracy of the biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis.ResultsA total of 326 patients with severe sepsis (21.7%) or septic shock (79.3%) were enrolled with a 28-day mortality rate of 31.0%. Only MR-proADM and lactate were associated with mortality in the multivariate analysis: hazard ratio 8.5 versus 3.4 (p < 0.001). MR-proADM showed the best AUROC for mortality prediction at 28 days in the analysis over the entire cohort (AUROC [95% CI] 0.79 [0.74–0.84]) (p < 0.001). When patients were stratified by the degree of organ failure, MR-proADM was the only biomarker to predict mortality in all severity groups (SOFA ≤ 6, SOFA = 7–12, and SOFA ≥ 13), AUROC [95% CI] of 0.75 [0.61–0.88], 0.74 [0.66–0.83] and 0.73 [0.59–0.86], respectively (p < 0.05). All patients with MR-proADM concentrations ≤0.88 nmol/L survived up to 28 days. In patients with SOFA ≤ 6, the addition of MR-proADM to the SOFA score increased the ability of SOFA to identify non-survivors, AUROC [95% CI] 0.70 [0.58–0.82] and 0.77 [0.66–0.88], respectively (p < 0.05 for both).ConclusionsThe performance of prognostic biomarkers in sepsis is highly influenced by disease severity. MR-proADM accuracy to predict mortality is not affected by the degree of organ failure. Thus, it is a good candidate in the early identification of sepsis patients with moderate disease severity but at risk of mortality.Electronic supplementary materialThe online version of this article (doi:10.1186/s13613-017-0238-9) contains supplementary material, which is available to authorized users.

Zoonotic hepatitis E, mainly caused by hepatitis E virus (HEV) genotype (gt) 3, is a foodborne disease that has emerged in Europe in recent decades. The main animal reservoir for genotype 3 is domestic pigs. Pig liver and liver derivates are considered the major risk products, and studies focused on the presence of HEV in pig muscles are scarce. The objective of the present study was to evaluate the presence of HEV in different organs and tissues of 45 apparently healthy pigs from nine Spanish slaughterhouses (50% national production) that could enter into the food supply chain. Anti-HEV antibodies were evaluated in serum by an ELISA test. Ten samples from each animal were analyzed for the presence of HEV RNA by reverse transcription realtime PCR (RT-qPCR). The overall seroprevalence obtained was 73.3% (33/45). From the 450 samples analyzed, a total of 26 RT-qPCR positive samples were identified in the liver (7/45), feces (6/45), kidney (5/45), heart (4/45), serum (3/45), and diaphragm (1/45). This is the first report on detection of HEV RNA in kidney and heart samples of naturally infected pigs. HEV RNA detection was negative for rib, bacon, lean ham, and loin samples. These findings indicate that pig meat could be considered as a low risk material for foodborne HEV infection.

The benefit of influenza vaccines is difficult to estimate due to the complexity of accurately assessing the burden of influenza. To improve the efficacy of influenza vaccines, vaccine manufacturers have developed quadrivalent influenza vaccine (QIV) formulations for seasonal vaccination by including both influenza B lineages. Three parallel approaches for producing influenza vaccines are attracting the interest of many vaccine manufacturing companies. The first and oldest is the conventional egg-derived influenza vaccine, which is used by the current licensed influenza vaccines. The second approach is a cell culture-derived influenza vaccine, and the third and most recent is synthetic vaccines. Here, we analyze the difficulties with vaccines production in eggs and compare this to cell culture-derived influenza vaccines and discuss the future of cell culture-derived QIVs.