Severe malaria in Europe: an 8-year multi-centre observational study.

BACKGROUND: Malaria remains one of the most serious infections for travellers to tropical countries. Due to the lack of harmonized guidelines a large variety of treatment regimens is used in Europe to treat severe malaria. METHODS: The European Network for Tropical Medicine and Travel Health (TropNet) conducted an 8-year, multicentre, observational study to analyse epidemiology, treatment practices and outcomes of severe malaria in its member sites across Europe. Physicians at participating TropNet centres were asked to report pseudonymized retrospective data from all patients treated at their centre for microscopically confirmed severe Plasmodium falciparum malaria according to the 2006 WHO criteria. RESULTS: From 2006 to 2014 a total of 185 patients with severe malaria treated in 12 European countries were included. Three patients died, resulting in a 28-day survival rate of 98.4%. The majority of infections were acquired in West Africa (109/185, 59%). The proportion of patients treated with intravenous artesunate increased from 27% in 2006 to 60% in 2013. Altogether, 56 different combinations of intravenous and oral drugs were used across 28 study centres. The risk of acute renal failure (36 vs 17% p = 0.04) or cerebral malaria (54 vs 20%, p = 0.001) was significantly higher in patients ≥60 years than in younger patients. Respiratory distress with the need for mechanical ventilation was significantly associated with the risk of death in the study population (13 vs 0%, p = 0.001). Post-artemisinin delayed haemolysis was reported in 19/70 (27%) patients treated with intravenous artesunate. CONCLUSION: The majority of patients with severe malaria in this study were tourists or migrants acquiring the infection in West Africa. Intravenous artesunate is increasingly used for treatment of severe malaria in many European treatment centres and can be given safely to European patients with severe malaria. Patients treated with intravenous artesunate should be followed up to detect and manage late haemolytic events.

Hemolysis after Oral Artemisinin Combination Therapy for Uncomplicated Plasmodium falciparum Malaria.

Episodes of delayed hemolysis 2-6 weeks after treatment of severe malaria with intravenous artesunate have been described. We performed a prospective observational study of patients with uncomplicated malaria to investigate whether posttreatment hemolysis also occurs after oral artemisinin-based combination therapy. Eight of 20 patients with uncomplicated malaria who were given oral artemisinin-based combination therapy met the definition of posttreatment hemolysis (low haptoglobin level and increased lactate dehydrogenase level on day 14). Five patients had hemolysis persisting for 1 month. Patients with posttreatment hemolysis had a median decrease in hemoglobin level of 1.3 g/dL (interquartile range 0.3-2.0 g/dL) in the posttreatment period, and patients without posttreatment hemolysis had a median increase of 0.3 g/dL (IQR -0.1 to 0.7 g/dL; p = 0.002). These findings indicate a need for increased vigilance for hemolytic events in malaria patients, particularly those with predisposing factors for anemia.

Intravenous Artesunate Reduces Parasite Clearance Time, Duration of Intensive Care, and Hospital Treatment in Patients With Severe Malaria in Europe: The TropNet Severe Malaria Study.

Intravenous artesunate improves survival in severe malaria, but clinical trial data from nonendemic countries are scarce. The TropNet severe malaria database was analyzed to compare outcomes of artesunate vs quinine treatment. Artesunate reduced parasite clearance time and duration of intensive care unit and hospital treatment in European patients with imported severe malaria.

Blood culture positive Nocardia asteroides infection: a case report.

We report a case of nocardiosis in a patient with several risk factors for this rare infection. Radiologically, the patient's multiple lung abscesses were misinterpreted as pulmonary metastases. Diagnosis was finally reached by the growth of Nocardia asteroides in two different blood culture sets. Nocardia bacteraemia is a rare clinical event. Despite initiation of an effective antibiotic therapy, the patient died. Autopsy revealed disseminated nocardial abscesses in the lungs, the kidneys and the brain.

Focused ion beam induced synthesis of antimony nanowires for gas sensor applications.

In this paper the formation of antimony (Sb) nanowires (NWs) by a focused Ga ion beam approach and their gas sensing capability is reported. The NWs with uniform diameters of only 25 nm and lengths up to several microns are synthesized at predefined positions at room temperature in an ion beam induced self-assembling process. Then individual Sb-NWs are deposited on insulating substrates and provided with gold electrodes. Subsequently sensing characteristics of individual Sb-NWs are investigated at room temperature for H(2)O, CO, H(2), He, O(2) and ethanol over a wide concentration range. The Sb-NWs exhibit selective sensing properties for ethanol and H(2)O with exceptional sensitivities of more than 17,000 and 60,000, respectively.

Atypical self-activation of Ga dopant for Ge nanowire devices.

In this Letter we report the atypical self-activation of gallium (Ga) implanted by focused ion beam (FIB) into germanium nanowires (Ge-NWs). By FIB implantation of 30 keV Ga(+) ions at room temperature, the Ge-NW conductivity increases up to 3 orders of magnitude with increasing ion fluence. Cu(3)Ge heterostructures were formed by diffusion to ensure well-defined contacts to the NW and enable two point I/V measurements. Additional four point measurements prove that the conductivity enhancement emerges from the modification of the wires themselves and not from contact property modifications. The Ga distribution in the implanted Ge-NWs was measured using atom probe tomography. For high ion fluences, and beginning amorphization of the NWs, the conductivity decreases exponentially. Temperature dependent conductivity measurements show strong evidence for an in situ doping of the Ge-NWs without any further annealing. Finally the feasibility of improving the device performance of top-gated Ge-NW MOSFETs by FIB implantation was shown.

Ultra-fast vapour-liquid-solid synthesis of Si nanowires using ion-beam implanted gallium as catalyst.

The feasibility of gallium as a catalyst for vapour-liquid-solid (VLS) nanowire (NW) growth deriving from an implantation process in silicon by a focused ion beam (FIB) is investigated. Si(100) substrates are subjected to FIB implantation of gallium ions with various ion fluence rates. NW growth is performed in a hot wall chemical vapour deposition (CVD) reactor at temperatures between 400 and 500 °C with 2% SiH(4)/He as precursor gas. This process results in ultra-fast growth of (112)- and (110)-oriented Si-NWs with a length of several tens of micrometres. Further investigation by transmission electron microscopy indicates the presence of a NW core-shell structure: while the NW core yields crystalline structuring, the shell consists entirely of amorphous material.

No rebound of morbidity following intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Gabon.

In the context of a trial studying intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants in Lambaréné, Gabon, children aged 18-30 months were followed up after having received their last dose at an age of 15 months. In the intention-to-treat population, the protective efficacy against all malaria episodes was -18.0 (95% confidence interval, -97.4 to 29.5; P = .529). The protective efficacy against first or only anemia episode was -45.3 (95% confidence interval, -234.5 to 36.3; P=.375). The protective efficacies were negative and were not statistically significant. These results do not appear to support the concept of a rebound effect after intermittent preventive sulfadoxine-pyrimethamine treatment of malaria in infants. Clinical trials registration. NCT00167843.

In vitro activity of pyronaridine against Plasmodium falciparum and comparative evaluation of anti-malarial drug susceptibility assays.

BACKGROUND: Pyronaridine, a Mannich base anti-malarial with high efficacy against drug resistant Plasmodium falciparum, is currently evaluated as a fixed dose combination with artesunate for the treatment of uncomplicated malaria. In this study, the in vitro activity of pyronaridine against clinical isolates of P. falciparum from Lambaréné, Gabon, was assessed in order to obtain baseline data on its activity prior to its future use in routine therapy. Moreover, follow-up assessment on the in vitro activity of chloroquine, artesunate and quinine was performed. METHODS: In vitro response of field isolates of P. falciparum to pyronaridine, chloroquine, artesunate and quinine was assessed using the traditional WHO microtest. In addition, the histidine-rich protein 2 (HRP-2) assay was performed and evaluated for its future implementation for follow-up of drug susceptibility testing. RESULTS: Pyronaridine exhibited a high in vitro activity against P. falciparum, with a geometric mean cut-off concentration of 9.3 nmol/l. Fifty percent effective concentrations were 1.9 nmol/l and 2.0 nmol/l in the WHO microtest and HRP-2 assay, respectively. Results matched closely in vivo findings from a recent clinical trial on pyronaridine-artesunate treatment. One isolate showed diminished sensitivity to artesunate. For chloroquine and quinine resistance levels were comparable to prior studies from Lambaréné. Results from the novel HRP-2 assay corresponded well to those obtained by the WHO microtest. CONCLUSION: Pyronaridine is highly active in chloroquine-resistant parasites and seems a promising partner drug for artemisinin-based combination therapy in Africa.

Orientation specific synthesis of kinked silicon nanowires grown by the vapour-liquid-solid mechanism.

Kinked silicon nanowires (Si-NWs) were synthesized in a well reproducible manner using gold nanocluster-catalyzed quasi-one-dimensional growth on Si(111) substrates with silane (SiH(4)) as the precursor gas. The kinking is considered to be due to the change in the growth direction induced by the sudden change of the pressure during Si-NW synthesis. Structural high resolution transmission electron microscopy (HRTEM) characterization of the sample shows that epitaxial Si-NWs synthesized on Si(111) substrates at a total pressure of 3 mbar grow along the {111} direction, while the ones at 15 mbar favour the {112} direction. By dynamically changing the system pressure during the growth process morphological changes of the NW growth directions along their length have been shown, resulting in kinked nanowires. The crystallographic orientation relation of the kinking between the 3 and 15 mbar ranges has been analysed by TEM. It is shown that no defects or grain boundaries in the intersection between the two sections of the Si-NWs are necessary to form such kinks between different wire directions.

RE: 'Streptococcus pluranimalium: A novel human pathogen?'

Streptococcus pluranimalium as a novel human pathogen has been reported by several authors in various contexts. In all reported cases in humans the microorganism was detected by the Vitek2®. The great advances with the introduction of new analytical techniques such as MALDI-TOF or 16S rRNA analysis enabled a more detailed discrimination of pathogens such as these nonhemolytic streptococci. In the cases of such similar gene sequences such techniques are absolutely essential to identify the exact strain for this highly conserved 16S rRNA gene. However, until now neither a sequence analysis of the 16S rRNA gene nor PCR nor MALDI-TOF techniques could define Streptococcus pluranimalium in humans. We conclude that according to our best present knowledge there exists no conclusive evidence for a human infection of Streptococcus pluranimalium even when using most advanced and exact identification techniques until now.

Schistosomiasis in European Travelers and Migrants: Analysis of 14 Years TropNet Surveillance Data.

Schistosomiasis remains one of the most prevalent parasitic diseases worldwide and the infection is frequently found in travelers and migrants. The European Network for Tropical Medicine and Travel Health conducted a sentinel surveillance study on imported schistosomiasis between 1997 and 2010. This report summarizes epidemiological and clinical data from 1,465 cases of imported schistosomiasis. Direct pathogen detection and serology were the main diagnostic tools applied. Of these, 486 (33%) cases were identified among European travelers, 231 (16%) among long-term expatriates, and 748 (51%) among non-European immigrants. Overall, only 18.6% of travelers had received pretravel advice; 95% of infections were acquired in the African region. On species level, Schistosoma mansoni was identified in 570 (39%) and Schistosoma haematobium in 318 (22%) cases; 57.5% of patients were symptomatic. Acute symptoms were reported in 27% of patients leading to earlier presentation within 3 months. Praziquantel was used in all patients to treat schistosomiasis. Many infections were detected in asymptomatic patients. In 47.4% of asymptomatic patients infection was detected by microscopy and in 39% by serology or antigen testing. Schistosomiasis remains a frequent infection in travelers and migrants to Europe. Travelers should be made aware of the risk of schistosomiasis infection when traveling to sub-Saharan Africa. Posttravel consultations particularly for returning expatriates are useful given the high potential for detecting asymptomatic infections.

Coughing and fever after surfing in Central America.

We report the case of a 19-year-old surfer, returning from Central America, who presented with chronic cough. The X-ray and full blood count, which had been performed in Costa Rica, were without pathology; laboratory parameters showed slightly increased C-reactive protein (59 mg/l). Malaria was excluded by thick smear. Immune serological tests for typhus, paratyphus, brucellosis, rickettsioses, leptospirosis and dengue fever were negative. An ambulant antimicrobial treatment was without any clinical effect. A computer tomography of the thorax showed a solid lesion (30 × 20 mm, middle lobe of the right lung). The patient rejected a bronchoscopic examination. He decided to be treated after his return to Austria. Here, we could substantiate a pulmonal histoplasmosis by a positive immune diffusion test. The patient was successfully treated with itraconazole.

Synthesis and electrical characterization of intrinsic and in situ doped Si nanowires using a novel precursor.

Perchlorinated polysilanes were synthesized by polymerization of tetrachlorosilane under cold plasma conditions with hydrogen as a reducing agent. Subsequent selective cleavage of the resulting polymer yielded oligochlorosilanes Si(n)Cl(2) (n) (+2) (n = 2, 3) from which the octachlorotrisilane (n = 3, Cl(8)Si(3), OCTS) was used as a novel precursor for the synthesis of single-crystalline Si nanowires (NW) by the well-established vapor-liquid-solid (VLS) mechanism. By adding doping agents, specifically BBr(3) and PCl(3), we achieved highly p- and n-type doped Si-NWs by means of atmospheric-pressure chemical vapor deposition (APCVD). These as grown NWs were investigated by means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM), as well as electrical measurements of the NWs integrated in four-terminal and back-gated MOSFET modules. The intrinsic NWs appeared to be highly crystalline, with a preferred growth direction of [111] and a specific resistivity of ρ = 6 kΩ·cm. The doped NWs appeared to be [112] oriented with a specific resistivity of ρ = 198 mΩ·cm for p-type Si-NWs and ρ = 2.7 mΩ·cm for n-doped Si-NWs, revealing excellent dopant activation.

In vitro activity of antifungal drugs against Plasmodium falciparum field isolates.

The increasing resistance of the malaria parasite Plasmodium falciparum to currently available drugs necessitates a continuous effort to develop new antimalarial agents. We therefore aimed to assess the in vitro activity of the antifungal drugs clotrimazole, fluconazole, ketoconazole, itraconazole, voriconazole, flucytosine, amphotericin B, and caspofungin against field isolates of P. falciparum from Lambaréné, Gabon. Using the histidin-rich protein 2 (HRP-2) assay we determined the drug susceptibility (EC(50), EC(90)) of 16 field isolates obtained from outpatients attending the Albert Schweitzer Hospital in Lambaréné, Gabon. For fluconazole, itraconazole and caspofungin the in vitro growth inhibition of these drugs is reported for the first time. Our data indicate that clotrimazole, fluconazole, itraconazole and caspofungin show median EC(50) values of 3.1 µg/mL, 1.9 µg/mL, 1.1 µg/mL and 1.1 µg/mL respectively. Ketoconazole, voriconazole, flucytosine and amphotercin B showed no relevant growth inhibition within the range of drug concentrations used in this study.

Synthesis of single-crystalline Zn metal nanowires utilizing cold-wall physical vapor deposition.

Zinc metal nanowires (NWs) of two different morphologies have been synthesized in a cold-wall physical vapor deposition (CWPVD) chamber at high vacuum conditions and growth temperatures of 150 degrees C. Substrates initially seeded by gold or platinum crystals show NWs of wool-like and/or unidirectional morphologies. Transmission electron microscopy (TEM) studies revealed that the rodlike NWs consist of single-crystalline Zn covered with a thin native oxide. NWs of wool-like morphology are suppressed using platinum as the seed metal. NW growth proceeds via vapor-solid (VS) kinetics without any catalyst particles on the wire tips. The highest observed growth rates exceed the Zn deposition rate by factors up to 860, indicating the dominant role of surface diffusion of Zn adatoms, also along the NWs. The surface diffusion length of Zn adatoms on the NW side facet is determined to be 39 mum. Direct impingement of precursor atoms on the NW tip is not significant for the growth process.

Randomized controlled trial of fosmidomycin-clindamycin versus sulfadoxine-pyrimethamine in the treatment of Plasmodium falciparum malaria.

Fosmidomycin-clindamycin therapy given every 12 h for 3 days was compared with a standard single oral dose of sulfadoxine-pyrimethamine. The two treatments showed comparably good tolerabilities and had an identical high degree of efficacy of 94% in a randomized trial carried out with 105 Gabonese children aged 3 to 14 years with uncomplicated malaria. These antimalarials merit further clinical exploration.

Intermittent preventive treatment against malaria in infants in Gabon--a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Intermittent preventive treatment aims to maximize the protective effects of malaria chemoprophylaxis while minimizing the deleterious effects. METHODS: In Gabon, 1189 infants received either sulfadoxine-pyrimethamine (SP; 250 and 12.5 mg, respectively) or placebo at 3, 9, and 15 months of age. Children were actively followed-up until 18 months of age. RESULTS: In the intention-to-treat population at 18 months of follow-up, 84 children (17%) in the SP group had > or =1 episode of anemia, versus 108 (21%) in the placebo group (protective efficacy, 22% [95% confidence interval {CI}, -1% to 40%]; P=.06). In the intervention group, there were 66 episodes during 485 person-years at risk, compared with 79 episodes during 497 years in the placebo group (protective efficacy, 17% [95% CI, -24% to 45%; P=.36). The effects were similar at 12 months of follow-up. The study drug was safe and well tolerated. CONCLUSIONS: The intervention was efficacious, producing a reduction in risk for anemia but a smaller effect against malaria. It is a valuable additional tool to control malaria in a highly vulnerable age group. Remaining important questions are currently being addressed in further studies. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00167843.