BackgroundEbola virus disease (EVD) is a highly lethal condition for which no specific treatment has proven efficacy. In September 2014, while the Ebola outbreak was at its peak, the World Health Organization released a short list of drugs suitable for EVD research. Favipiravir, an antiviral developed for the treatment of severe influenza, was one of these. In late 2014, the conditions for starting a randomized Ebola trial were not fulfilled for two reasons. One was the perception that, given the high number of patients presenting simultaneously and the very high mortality rate of the disease, it was ethically unacceptable to allocate patients from within the same family or village to receive or not receive an experimental drug, using a randomization process impossible to understand by very sick patients. The other was that, in the context of rumors and distrust of Ebola treatment centers, using a randomized design at the outset might lead even more patients to refuse to seek care.Therefore, we chose to conduct a multicenter non-randomized trial, in which all patients would receive favipiravir along with standardized care. The objectives of the trial were to test the feasibility and acceptability of an emergency trial in the context of a large Ebola outbreak, and to collect data on the safety and effectiveness of favipiravir in reducing mortality and viral load in patients with EVD. The trial was not aimed at directly informing future guidelines on Ebola treatment but at quickly gathering standardized preliminary data to optimize the design of future studies.Methods and FindingsInclusion criteria were positive Ebola virus reverse transcription PCR (RT-PCR) test, age ≥ 1 y, weight ≥ 10 kg, ability to take oral drugs, and informed consent. All participants received oral favipiravir (day 0: 6,000 mg; day 1 to day 9: 2,400 mg/d). Semi-quantitative Ebola virus RT-PCR (results expressed in “cycle threshold” [Ct]) and biochemistry tests were performed at day 0, day 2, day 4, end of symptoms, day 14, and day 30. Frozen samples were shipped to a reference biosafety level 4 laboratory for RNA viral load measurement using a quantitative reference technique (genome copies/milliliter). Outcomes were mortality, viral load evolution, and adverse events. The analysis was stratified by age and Ct value. A “target value” of mortality was defined a priori for each stratum, to guide the interpretation of interim and final analysis.Between 17 December 2014 and 8 April 2015, 126 patients were included, of whom 111 were analyzed (adults and adolescents, ≥13 y, n = 99; young children, ≤6 y, n = 12). Here we present the results obtained in the 99 adults and adolescents. Of these, 55 had a baseline Ct value ≥ 20 (Group A Ct ≥ 20), and 44 had a baseline Ct value < 20 (Group A Ct < 20). Ct values and RNA viral loads were well correlated, with Ct = 20 corresponding to RNA viral load = 7.7 log10 genome copies/ml. Mortality was 20% (95% CI 11.6%–32.4%) in Group A Ct ≥ 20 and 91% (95% CI 78.8%–91.1%) in Group A Ct < 20. Both mortality 95% CIs i...

Bacillus anthracis is a Gram-positive, spore-forming bacterium, which causes anthrax, an often lethal disease of animals and humans. Although the disease has been well studied since the nineteenth century, it has witnessed a renewed interest during the past decade, due to its use as a bioterrorist agent in the fall of 2001 in the USA. A number of techniques aimed at rapidly detecting B. anthracis, in environmental samples as well as in point-of-care settings for humans suspected of exposure to the pathogen, are now available. These technologies range from culture-based methods to portable DNA amplification devices. Despite recent developments, specific identification of B. anthracis still remains difficult because of its phenotypic and genotypic similarities with other Bacillus species. Accordingly, many efforts are being made to improve the specificity of B. anthracis identification. This mini-review discusses the current challenges around B. anthracis identification, not only in reach-back laboratories but also in the field (in operational conditions).

Microbiological cultures are moderately sensitive for diagnosing prosthetic joint infection (PJI). This study was conducted to determine whether amplificationbased DNA methods applied on intraoperative samples could enhance PJI diagnosis compared with culture alone in routine surgical practice. Revision arthroplasty was performed for suspected PJI (n ‫؍‬ 41) and osteoarthrosis control (n ‫؍‬ 28) patients , and a diagnosis of PJI was confirmed in 34 patients. Amplification by polymerase chain reaction was performed on both 16S ribosomal DNA universal target genes and femA Staphylococcus-specific target genes. Species identification was achieved through amplicon sequencing. Amplification of the femA gene led to subsequent testing for methicillin resistance by amplification of the mecA gene. Microbiological and molecular assays identified a causative organism in 22 of 34 patients (64.7%) and in 31 of 34 patients (91.2%), respectively. In 18 of the 22 culture-positive patients, molecular and microbiological results were concordant for bacterial genus , species , and/or methicillin resistance. Bacterial agents were identified only by molecular methods in nine PJI patients , including seven who were receiving antibiotics at the time of surgery and one with recent but not concomitant antibiotherapy. DNA-based methods were found to effectively complement microbiological methods , without interfering with existing procedures for sample collection , for the identification of causative pathogens from intraoperative PJI samples , especially in patients with recent or concomitant antibiotherapy. (J Mol

BackgroundThe rate of antimicrobial resistant isolates among pathogens causing urinary tract infections (UTIs) in Democratic Republic of Congo (DRC) is not known. The aim of the current study was to determine this rate at the Bukavu Provincial General Hospital (province of South-Kivu, DRC).FindingsA total of 643 isolates (both from inpatients and outpatients) collected from September 2012 to August 2013 were identified using biochemical methods, and tested for antimicrobial susceptibility. The isolates were further screened for Extended-Spectrum Beta-Lactamases (ESBL) production. Beta-lactamase AmpC phenotype was investigated in 20 antibiotic-resistant isolates.Escherichia coli (58.5%), Klebsiella spp. (21.9%) and Enterobacter spp. (16.2%) were the most frequent uropathogens encountered. Rare uropathogens included Citrobacter spp., Proteus spp., and Acinetobacter spp. Resistance was significantly more present in inpatients isolates (22.1% of isolates) when compared to outpatients isolates (8.4% of isolates), (p-value <0.001). Antibiotic-resistant isolates displayed resistance to common antimicrobial drugs used for UTIs treatment in South Kivu province, namely: ciprofloxacin, ampicillin and third generation cephalosporins. ESBL-phenotype was present in 92.9% of antibiotic-resistant isolates. Only amikacin, nitrofurantoin and imipenem displayed satisfactory activity against antibiotic resistant isolates.ConclusionsThis study confirms the presence of antibiotic-resistant uropathogens (mainly ESBL-producers isolates) at the Bukavu General Hospital. This study should serve as a wake-up call and help to raise awareness about the threat to public health of antibiotic resistance in this DRC province.