Estimating true incidence of O157 and non-O157 Shiga toxin-producing Escherichia coli illness in Germany based on notification data of haemolytic uraemic syndrome.

Shiga toxin-producing Escherichia coli (STEC) is an important cause of gastroenteritis (GE) and haemolytic uraemic syndrome (HUS). Incidence of STEC illness is largely underestimated in notification data, particularly of serogroups other than O157 ('non-O157'). Using HUS national notification data (2008-2012, excluding 2011), we modelled true annual incidence of STEC illness in Germany separately for O157 and non-O157 STEC, taking into account the groups' different probabilities of causing bloody diarrhoea and HUS, and the resulting difference in their under-ascertainment. Uncertainty of input parameters was evaluated by stochastic Monte Carlo simulations. Median annual incidence (per 100 000 population) of STEC-associated HUS and STEC-GE was estimated at 0·11 [95% credible interval (CrI) 0·08-0·20], and 35 (95% CrI 12-145), respectively. German notification data underestimated STEC-associated HUS and STEC-GE incidences by factors of 1·8 and 32·3, respectively. Non-O157 STEC accounted for 81% of all STEC-GE, 51% of all bloody STEC-GE and 32% of all STEC-associated HUS cases. Non-O157 serogroups dominate incidence of STEC-GE and contribute significantly to STEC-associated HUS in Germany. This might apply to many other countries considering European surveillance data on HUS. Non-O157 STEC should be considered in parallel with STEC O157 when searching aetiology in patients with GE or HUS, and accounted for in modern surveillance systems.

Polyglycidol-based metal adhesion promoters.

Hydrophilic adhesion promoters that facilitate intimate binding between metals and polymers are an important class of materials with a wide variety of applications in biomedical coatings. Currently, non-poly(meth-)acrylate based hydrophilic polymeric adhesives are unavailable. Here, we report the preparation of such adhesion-promoters based on linear polyglycidol for biomedical applications. The adhesion promoting polymer is prepared from partly phosphonoethylated polyglycidol in three steps. First, the remaining hydroxyl groups of the polyglycidol backbone are reacted with acryloyl chloride; secondly, the phosphonate groups are chemoselectively dealkylated using bromotrimethylsilane. Finally, the bis(trimethylsilyl)phosphonate intermediate is converted to the phosphonic acid through ethanolysis. The reaction conditions of each synthetic step are optimized individually and the products are characterized by 1H, 31P NMR and SEC analysis. The optimized reaction conditions are applied to establish a straightforward one-pot reaction, resulting in an ethanolic formulation of the adhesion promoter, which can be used immediately for the coating application. Special attention is paid to the stability of the intermediates, the chemoselectivity of the reactions and the shelf-life of the product. 1H NMR spectroscopy reveals hydrolytic instability of the product under ambient conditions; however, the polymers are sufficiently stable in dry ethanol for at least 14 days. The combination of this hydrophilic polymer with acrylate and phosphonic acid groups constitutes a versatile platform technology for the preparation of thin primer coatings on metal substrates for biomedical applications. The phosphonic acid residues assure strong binding to stainless steel wires and the acrylates can be addressed by UV light to enable crosslinking, thus improving mechanical stability and adhesion between the substrate and a biomedical hydrogel coating. The quality of the adhesion promotion to stainless steel wires is verified by using a lubricious, hydrogel top coat and by evaluating friction and wear resistance of this total coating system. Constant values for friction and wear are obtained, proving the applicability of phosphonic acid-functionalized polyglycidols as metal adhesion promoters for biomedical applications.

Hybrid GaN/organic microstructured light-emitting devices via ink-jet printing.

We report what we believe to be the first use of organic nanostructures for efficient colour conversion of gallium nitride light emitting diodes (LEDs). The particular nanomaterials, based on star-shaped truxene oligofluorenes, offer an attractive alternative to inorganic colloidal quantum dots in the search for novel and functional 'nanophosphors'. The truxenes have been formed into a composite with photoresist and ink-jet printed onto microstructured gallium nitride LEDs, resulting in a demonstrator hybrid microdisplay technology with pixel size approximately 32 microm. The output power density of the hybrid device was measured to be approximately 8.4 mW/cm(2) per pixel at driving current density of 870.8A/cm(2) and the efficiency of colour conversion at drive current of 7 mA was estimated to be approximately 50%.

Integration by self-aligned writing of nanocrystal/epoxy composites on InGaN micro-pixelated light-emitting diodes.

We report on the integration of monodisperse semiconductor nanocrystal (NC) color converters onto gallium nitride ultraviolet micro-pixelated light-emitting diodes ('micro-LEDs'). Integration is achieved in a 'self-aligned' process by forming a nanocomposite of the respective NCs in a photocurable epoxy polymer. Blue, green, yellow and red NC/epoxy blend microstructures have been successfully integrated onto micro-pixelated LEDs by this technique and utilised for color conversion, resulting in a five color emission single chip. Optical output power density of up to about 166 mW/cm2 is measured; spectral emission at 609 nm gives an estimated optical-to-optical conversion as high as 18.2% at 30 mA driving current.

Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey.

BACKGROUND: Antibodies to glycoprotein (GP) IIb-IIIa and/or HLA may render platelet transfusions ineffective to stop bleeding or to cover surgery in patients with Glanzmann's thrombasthenia (GT). Anecdotal reports suggest recombinant factor (rF)VIIa might be a therapeutic alternative in these situations. OBJECTIVES: An international survey was conducted to evaluate further the efficacy and safety of rFVIIa in GT patients. PATIENTS: We analyzed the use of rFVIIa during 34 surgical/invasive procedures and 108 bleeding episodes in 59 GT patients including 29 with current or previous antiplatelet antibodies, and 23 with a history of refractoriness to platelet transfusion. RESULTS: rFVIIa was effective in 29 of the 31 evaluable procedures, and in 77 of the 103 evaluable bleeding episodes of which eight had a recurrence. A significantly higher success rate was observed in severe bleeding episodes when an arbitrarily defined 'optimal regimen' derived from the Canadian pilot study results (> or = 80 micro g kg(-1) rFVIIa/injection, dosing interval < or = 2.5 h, three or more doses before failure declaration) was used compared with other regimens (77%; 24/31 vs. 48%, 19/40; chi(2), P = 0.010). Patients given maintenance doses had significantly fewer recurrences within 48 h of bleed cessation compared with those not given any (Fisher's exact test, P = 0.022). One thromboembolic event and one blood clot in the ureter occurring in surgical patients following prolonged continuous infusion of high-dose rFVIIa and antifibrinolytic drug use have been previously reported. CONCLUSION: rFVIIa seems a potential alternative to platelet transfusion in GT patients, particularly in those with antiplatelet antibodies and/or platelet refractoriness.

Ebola virus glycoprotein demonstrates differential cellular localization in infected cell types of nonhuman primates and guinea pigs.

BACKGROUND: In vitro studies have previously shown that Ebola virus glycoprotein (GP) is rapidly processed and largely released from infected cells, whereas other viral proteins, such as VP40, accumulate within cells. OBJECTIVE: To determine infected cell types in which Ebola virus GP and VP40, individually, localize in vivo. METHODS: Immunohistochemistry and in situ hybridization using GP- and VP40-specific antibodies and genetic probes were used to analyze archived tissues of experimentally infected nonhuman primates and guinea pigs and Vero E6 and 293 cells infected in vitro. RESULTS: The GP antigen was consistently present in hepatocytes, adrenal cortical cells, fibroblasts, fibroblastic reticular cells, ovarian thecal cells, and several types of epithelial cells, but was not detected in macrophages and blood monocytes of animals, nor in Vero cells and 293 cells. All GP-positive and GP-negative cell types analyzed contained VP40 antigen and both GP and VP40 RNAs. CONCLUSIONS: Ebola virus GP appears to selectively accumulate in many cell types infected in vivo, but not in macrophages and monocytes. This finding suggests that many cell types may have a GP-processing pathway that differs from the pathway described by previous in vitro studies. Differential cellular localization of GP could be relevant to the pathogenesis of Ebola hemorrhagic fever.

Field investigations of an outbreak of Ebola hemorrhagic fever, Kikwit, Democratic Republic of the Congo, 1995: arthropod studies.

During the final weeks of a 6-month epidemic of Ebola hemorrhagic fever in Kikwit, Democratic Republic of the Congo, an extensive collection of arthropods was made in an attempt to learn more of the natural history of the disease. A reconstruction of the activities of the likely primary case, a 42-year-old man who lived in the city, indicated that he probably acquired his infection in a partly forested area 15 km from his home. Collections were made throughout this area, along the route he followed from the city, and at various sites in the city itself. No Ebola virus was isolated, but a description of the collections and the ecotopes involved is given for comparison with future studies of other outbreaks.

Safety and immunogenicity of a live-attenuated Junin (Argentine hemorrhagic fever) vaccine in rhesus macaques.

The safety and immunogenicity of Candid #1, a live-attenuated Junin virus vaccine, were evaluated in rhesus macaques. Candid #1 was inoculated subcutaneously in graded doses ranging from 16 to 127,200 plaque-forming units (PFU) into four groups of five animals each; four controls received saline. There was no significant effect of the immunization on any physical, hematologic, or biochemical parameter measured. Junin virus was recovered by cocultivation from peripheral blood mononuclear cells (PBMC) of 14 (70%) of 20 animals from 1 to 21 days after immunization; 27 (12%) of 223 PBMC samples that represented animals in all four dose groups were positive. In contrast, virus was recovered from the plasma of only two of 20 macaques (two of 225 samples [0.9%]), and only once (by amplification) from throat swabs. No evidence of reversion was detected in any blood isolate. All animals developed a detectable neutralizing antibody response following vaccination. These results indicate that Candid #1 is safe and immunogenic in nonhuman primates.

Candid No. 1 Argentine hemorrhagic fever vaccine protects against lethal Junin virus challenge in rhesus macaques.

The protective efficacy of Candid No. 1, a live-attenuated vaccine against Argentine hemorrhagic fever (AHF), was evaluated in non-human primates. Twenty rhesus macaques immunized 3 months previously with graded doses of Candid No. 1 (16-127, 000 PFU), as well as 4 placebo-inoculated controls, were challenged with 4.41 log10 PFU of virulent P3790 strain Junin virus. All controls developed severe clinical disease; 3 of 4 died. In contrast, all vaccinated animals were fully protected; none developed any signs of AHF during a 105-day follow-up period. Viremia and virus shedding were readily detected in all placebo-vaccinated controls, while virus could be recovered only once (by amplification) from throat swabs of 2 Candid No. 1 vaccinees on day 21. Vigorous secondary-type neutralizing and immunofluorescent antibody responses were seen in most vaccinees that had received 3 log10 PFU Candid No. 1 or fewer; all others, including those receiving 127,200 PFU, maintained relatively stable titers during follow-up. Candid No. 1 was highly immunogenic and fully protective against lethal Junin virus challenge in rhesus macaques, even at extremely low (16 PFU) vaccine doses.

Efficacy of chloramphenicol, enrofloxacin, and tetracycline for treatment of experimental Rocky Mountain spotted fever in dogs.

Dogs were experimentally inoculated with Rickettsia rickettsii to characterize the comparative efficacies of chloramphenicol, enrofloxacin, and tetracycline for the treatment of Rocky Mountain spotted fever (RMSF). All three antibiotics were equally effective in abrogating the clinical, hematologic, and vascular indicators of rickettsial infection. Antibiotic treatment for 24 h was sufficient to decrease the rickettsemia to levels below detection by Vero cell culture. Early treatment with all three antibiotics resulted in a similar decrease in antibody titer, but acute and convalescent serum samples taken at appropriate times would have still facilitated an accurate diagnosis of RMSF in all but one dog, which did not seroconvert. We conclude that chloramphenicol, enrofloxacin, and tetracycline are equally efficacious for treating experimental canine RMSF.