Explore the vast range of titles available.

A nanopore DNA sequencer is used for real-time genomic surveillance of the Ebola virus epidemic in the field in Guinea; the authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. Ebola virus genomics surveillance This paper reports the use of nanopore DNA sequencers (known as MinIONs) for real-time genomic surveillance of the Ebola virus epidemic, in the field in Guinea. The authors demonstrate that it is possible to pack a genomic surveillance laboratory in a suitcase and transport it to the field for on-site virus sequencing, generating results within 24 hours of sample collection. The Ebola virus disease epidemic in West Africa is the largest on record, responsible for over 28,599 cases and more than 11,299 deaths 1 . Genome sequencing in viral outbreaks is desirable to characterize the infectious agent and determine its evolutionary rate. Genome sequencing also allows the identification of signatures of host adaptation, identification and monitoring of diagnostic targets, and characterization of responses to vaccines and treatments. The Ebola virus (EBOV) genome substitution rate in the Makona strain has been estimated at between 0.87 × 10 −3 and 1.42 × 10 −3 mutations per site per year. This is equivalent to 16–27 mutations in each genome, meaning that sequences diverge rapidly enough to identify distinct sub-lineages during a prolonged epidemic 2 , 3 , 4 , 5 , 6 , 7 . Genome sequencing provides a high-resolution view of pathogen evolution and is increasingly sought after for outbreak surveillance. Sequence data may be used to guide control measures, but only if the results are generated quickly enough to inform interventions 8 . Genomic surveillance during the epidemic has been sporadic owing to a lack of local sequencing capacity coupled with practical difficulties transporting samples to remote sequencing facilities 9 . To address this problem, here we devise a genomic surveillance system that utilizes a novel nanopore DNA sequencing instrument. In April 2015 this system was transported in standard airline luggage to Guinea and used for real-time genomic surveillance of the ongoing epidemic. We present sequence data and analysis of 142 EBOV samples collected during the period March to October 2015. We were able to generate results less than 24 h after receiving an Ebola-positive sample, with the sequencing process taking as little as 15–60 min. We show that real-time genomic surveillance is possible in resource-limited settings and can be established rapidly to monitor outbreaks.

Infection with influenza A viruses (IAV) provokes activation of cellular defence mechanisms contributing to the innate immune and inflammatory response. In this process the cyclooxygenase-2 (COX-2) plays an important role in the induction of prostaglandin-dependent inflammation. While it has been reported that COX-2 is induced upon IAV infection, in the present study we observed a down-regulation at later stages of infection suggesting a tight regulation of COX-2 by IAV. Our data indicate the pattern-recognition receptor RIG-I as mediator of the initial IAV-induced COX-2 synthesis. Nonetheless, during on-going IAV replication substantial suppression of COX-2 mRNA and protein synthesis could be detected, accompanied by a decrease in mRNA half-life. Interestingly, COX-2 mRNA stability was not only imbalanced by IAV replication but also by stimulation of cells with viral RNA. Our results reveal tristetraprolin (TTP), which is known to bind COX-2 mRNA and promote its rapid degradation, as regulator of COX-2 expression in IAV infection. During IAV replication and viral RNA accumulation TTP mRNA synthesis was induced, resulting in reduced COX-2 levels. Accordingly, the down-regulation of TTP resulted in increased COX-2 protein expression after IAV infection. These findings indicate a novel IAV-regulated cellular mechanism, contributing to the repression of host defence and therefore facilitating viral replication.

Fatal Ebola virus disease is characterized by a high proportion of CD4 + and CD8 + T cells expressing the inhibitory molecules CTLA-4 and PD-1, correlating with high virus load; individuals who survive the infection exhibit lower expression of these inhibitory molecules and generate Ebola-specific CD8 + T cells, suggesting that dysregulation of the T cell response is a key component of Ebola virus disease pathophysiology. A marker for fatal Ebola César Muñoz-Fontela and colleagues have tracked the T cell response in individuals infected with Ebola virus in Guinea. Following patients from the time of their admission at the Ebola Treatment Centre in Guinea until their discharge or death, the authors identify an immune signature that is characteristic of fatal Ebola virus disease. In fatal infection, a high proportion of CD4 + and CD8 + cells expressed the inhibitory molecules CTLA-4 and PD-1, correlating with high virus load. By contrast, individuals who survived the infection showed lower expression of these inhibitory molecules, suggesting that dysregulation of the T cell response is a key component of Ebola virus disease pathophysiology. Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD 1 . In particular, very little is known about human immune responses to Ebola virus 2 , 3 . Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4 + and CD8 + T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.

In 2015, the laboratory at the Ebola treatment center in Coyah, Guinea, confirmed Ebola virus disease (EVD) in 286 patients. The cycle threshold (Ct) of an Ebola virus-specific reverse transcription-polymerase chain reaction assay and 13 blood chemistry parameters were measured on admission and during hospitalization. Favipiravir treatment was offered to patients with EVD on a compassionate-use basis. To reduce biases in the raw field data, we carefully selected 163 of 286 patients with EVD for a retrospective study to assess associations between potential risk factors, alterations in blood chemistry findings, favipiravir treatment, and outcome. The case-fatality rate in favipiravir-treated patients was lower than in untreated patients (42.5% [31 of 73] vs 57.8% [52 of 90]; P = .053 by univariate analysis). In multivariate regression analysis, a higher Ct and a younger age were associated with survival (P < .001), while favipiravir treatment showed no statistically significant effect (P = .11). However, Kaplan-Meier analysis indicated a longer survival time in the favipiravir-treated group (P = .015). The study also showed characteristic changes in blood chemistry findings in patients who died, compared with survivors. Consistent with the JIKI trial, this retrospective study revealed a trend toward improved survival in favipiravir- treated patients; however, the effect of treatment was not statistically significant, except for its influence on survival time.

To date there are no approved antiviral drugs for the treatment of Ebola virus disease (EVD). Based on our in vitro evidence of antiviral activity of interferon (IFN)-ß activity against Ebola virus, we conducted a single arm clinical study in Guinea to evaluate the safety and therapeutic efficacy of IFN β-1a treatment for EVD. Nine individuals infected with Ebola virus were treated with IFN β-1a and compared retrospectively with a matched cohort of 21 infected patients receiving standardized supportive care only during the same time period at the same treatment unit. Cognizant of the limitations of having treated only 9 individuals with EVD, the data collected are cautiously considered. When compared to supportive care only, IFN β-1a treatment seemed to facilitate viral clearance from the blood and appeared associated with earlier resolution of disease symptoms. Survival, calculated from the date of consent for those in the trial and date of admission from those in the control cohort, to the date of death, was 19% for those receiving supportive care only, compared to 67% for those receiving supportive care plus IFN β-1a. Given the differences in baseline blood viremia between the control cohort and the IFN-treated cohort, an additional 17 controls were included for a subset analysis, from other treatment units in Guinea, matched with the IFN-treated patients based on age and baseline blood viremia. Subset analyses using this expanded control cohort suggests that patients without IFN β-1a treatment were ~ 1.5–1.9 fold more likely to die than those treated. Viewed altogether the results suggest a rationale for further clinical evaluation of IFN β-1a.

Preterm birth is a highly prevalent phenomenon that was shown to be associated with mental stress during pregnancy (Rich-Edwards and Grizzard in Am J Obstet Gynecol 192(5 Suppl):S30–S35, 2005 ). We aimed to assess the effects of heart rate variability (HRV)-biofeedback in patients with preterm labour. Therefore, we conducted a controlled randomized parallel group study in 48 female patients aged 19–38 years (median = 29) with preterm labour at gestational week 24th–32nd (median = 29th). In this study, one group (n = 24) attended six sessions of HRV-biofeedback over 2 weeks whereas patients of the other group (n = 24) were assigned to control sessions. In the HRV-biofeedback treated group, perception of chronic stress was decreased 4 weeks after completion of training compared to baseline ( p  < 0.05) but there was no change in the control group. In the HRV-biofeedback group, preterm birth was seen in 3 patients (13 %) whereas in the control group, preterm delivery occurred in 8 patients (33 %, p  = n.s.). There was no difference in birth weight between groups and HRV remained unchanged. In conclusion, our study demonstrates that HRV-biofeedback can reduce chronic stress in patients with preterm labour when administered as an adjunct to routine care. However, it remains unclear whether stress reduction through HRV-biofeedback has a beneficial effect on preterm birth.