Gold Standard Cholera Diagnostics Are Tarnished by Lytic Bacteriophage and Antibiotics.

A fundamental, clinical, and scientific concern is how lytic bacteriophage, as well as antibiotics, impact diagnostic positivity. Cholera was chosen as a model disease to investigate this important question, because cholera outbreaks enable large enrollment, field methods are well established, and the predatory relationship between lytic bacteriophage and the etiologic agent Vibrio cholerae share commonalities across bacterial taxa. Patients with diarrheal disease were enrolled at two remote hospitals in Bangladesh. Diagnostic performance was assessed as a function of lytic bacteriophage detection and exposure to the first-line antibiotic azithromycin, detected in stool samples by mass spectrometry. Among diarrheal samples positive by nanoliter quantitative PCR (qPCR) for V. cholerae (n = 78/849), the odds that a rapid diagnostic test (RDT) or qPCR was positive was reduced by 89% (odds ratio [OR], 0.108; 95% confidence interval [CI], 0.002 to 0.872) and 87% (OR, 0.130; 95% CI, 0.022 to 0.649), respectively, when lytic bacteriophage were detected. The odds that an RDT or qPCR was positive was reduced by more than 99% (OR, 0.00; 95% CI, 0.00 to 0.28) and 89% (OR, 0.11; 95% CI, 0.03 to 0.44), respectively, when azithromycin was detected. Analysis of additional samples from South Sudan found similar phage effects on RDTs; antibiotics were not assayed. Cholera burden estimates may improve by accommodating for the negative effects of lytic bacteriophage and antibiotic exposure on diagnostic positivity. One accommodation is using bacteriophage detection as a proxy for pathogen detection. These findings have relevance for other diagnostic settings where bacterial pathogens are vulnerable to lytic bacteriophage predation.

The contribution of neighbours to an individual's risk of typhoid outcome.

An individual's risk of infection from an infectious agent can depend on both the individual's own risk and protective factors and those of individuals in the same community. We hypothesize that an individual's exposure to an infectious agent is associated with the risks of infection of those living nearby, whether their risks are modified by pharmaceutical interventions or by other factors, because of the potential for transmission from them. For example, unvaccinated individuals living in a highly vaccinated community can benefit from indirect protection, or living near more children in a typhoid-endemic region (where children are at highest risk) might result in more exposure to typhoid. We tested this hypothesis using data from a cluster-randomized typhoid vaccine trial. We first estimated each individual's relative risk of confirmed typhoid outcome using their vaccination status and age. We defined a new covariate, potential exposure, to be the sum of the relative risks of all who live within 100 m of each person. We found that potential exposure was significantly associated with an individual's typhoid outcome, and adjusting for potential exposure affected estimates of vaccine efficacy. We suggest that it is useful and feasible to adjust for spatially heterogeneous distributions of individual-level risk factors, but further work is required to develop and test such approaches.

Assessing the impact of travel restrictions on international spread of the 2014 West African Ebola epidemic.

The quick spread of an Ebola outbreak in West Africa has led a number of countries and airline companies to issue travel bans to the affected areas. Considering data up to 31 Aug 2014, we assess the impact of the resulting traffic reductions with detailed numerical simulations of the international spread of the epidemic. Traffic reductions are shown to delay by only a few weeks the risk that the outbreak extends to new countries.

Neuroprotection by the stable nitroxide Tempol during reperfusion in a rat model of transient focal ischemia.

OBJECT: The use of thrombolytic agents in the treatment of stroke has yielded surprisingly modest success, possibly because of reperfusion injury mediated by reactive oxygen species (ROS). Therefore, scavenging ROS may be of therapeutic value in the treatment of stroke. Nitroxides are low-weight superoxide dismutase mimics, which allows them to act as cell-permeable antioxidants. In this study the nitroxide 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol) is investigated to determine its ability to reduce reperfusion injury. METHODS: Male Sprague-Dawley rats weighing between 280 g and 350 g underwent middle cerebral artery occlusion with an intraluminal suture for 60 minutes. Regional cerebral blood flow, blood pressure, cerebral temperature, and rectal temperature were monitored during the procedure. After reperfusion, the animals were randomized to groups receiving blinded intravenous administration of either Tempol (10 mg/kg; eight animals) or vehicle (eight animals) over the first 20 minutes of reperfusion (Study I). In a second study to determine dose dependency, animals were randomized to groups receiving Tempol (20 mg/kg; eight animals), low-dose Tempol (5 mg/kg; eight animals), or vehicle (eight animals; Study II). The rats were killed after 4 hours of reperfusion, and brain sections were stained with 2,3,5 triphenyltetrazolium chloride. Infarct volumes were measured using digital imaging. Animals receiving Tempol had significantly reduced infarct volumes at doses of 20 mg/kg and 10 mg/kg compared with controls (49.01+/-18.22% reduction [p = 0.003] and 47.47+/-34.57 [p = 0.02], respectively). No significant differences in the physiological variables measured were observed between groups. CONCLUSIONS: Tempol provides significant neuroprotection after reperfusion in a rat model of transient focal ischemia. These results support the importance of ROS in reperfusion injury and encourage further study of this molecule as a therapeutic agent following thrombolysis.

Inhibition of Deamination of Arabinosylcytosine (NSC-63878) by Rhodium(II) Acetate.

The nobel metal "cage" complex, rhodium(II) acetate, was found to inhibit the deamination of the fraudulent nucleoside, arabinosylcytosine. Potent inhibition of a purified cytidine deaminase from mouse kidney was observed when either cytidine or arabinosylcytosine was used as substrate.

High-Density Er-Implanted GaN Optical Memory Devices.

Upconversion emission has been obtained from Er-focused ion-beam (FIB) implanted GaN. Visible green emission at the 522- and 546-nm range were excited with infrared (IR) laser sources at either 840 or 1000 nm, or with both lasers simultaneously. By implanting closely spaced patterns with the FIB, we demonstrated the concept of storing data in Er-implanted GaN. Information stored as data bits consists of patterns of implanted locations as logic 1 and unimplanted locations as logic 0. The photon upconversion process in Er ions is utilized to read the stored information. This process makes use of the IR lasers to excite visible emission. The integrated upconversion emission power was measured to be ~40 pW when pumped by a 840-nm laser at 265 mW and by a 1000-nm laser at 208 mW. Patterns as small as 0.5 mum were implanted and read. Three-dimensional optical memory based on rare-earth-doped semiconductors could in theory approach a storage capacity of 10(12) bits/cm(3).