Antibodies to pre-erythrocytic Plasmodium falciparum antigens and risk of clinical malaria in Kenyan children

BACKGROUND: IgG antibodies to pre-erythrocytic antigens are involved in prevention of infection and disease in animal models of malaria but have not been associated with protection against disease in human malaria. METHODS: Levels of IgG antibodies to circumsporozoite protein (CSP), liver-stage antigen type 1 (LSA-1), and thrombospondin-related adhesive protein (TRAP) were measured in 86 children in a malaria-holoendemic area of Kenya. The children were then monitored for episodes of clinical malaria for 52 weeks. RESULTS: Children with high levels of IgG antibodies to CSP, LSA-1, and TRAP had a decreased risk of clinical malaria (adjusted hazard ratio, 0.29; 95% confidence interval 0.10-0.81; P = .02), a lower incidence of clinical malaria (P=.006), protection from clinical malaria with a parasite level of \u3e or =4000 parasites/microL (P= .03), and a higher hemoglobin level at enrollment (P= .009), compared with children with lower antibody levels. Protection against malaria morbidity was associated primarily with antibodies to CSP and LSA-1. CONCLUSIONS: Kenyan children with high levels of IgG antibodies to the pre-erythrocytic antigens CSP, LSA-1, and TRAP have a lower risk of developing clinical malaria than children without high levels of these antibodies. The decreased risk of clinical malaria may be mediated in part by prevention of high-density parasitemia

State-of-the-art of design and operation of power systems with large amounts of wind power, summary of IEA Wind collaboration

An international forum for exchange of knowledge of power system impacts of wind power has been formed under the IEA Implementing Agreement on Wind Energy. The task “Design and Operation of Power Systems with Large Amounts of Wind Power” is analysing existing case studies from different power systems.There are a multitude of studies made and ongoing related to cost of wind integration. However, the results are not easy to compare. This paper summarises the results from 15 case studies

MADNESS: A Multiresolution, Adaptive Numerical Environment for Scientific Simulation

MADNESS (multiresolution adaptive numerical environment for scientific simulation) is a high-level software environment for solving integral and differential equations in many dimensions that uses adaptive and fast harmonic analysis methods with guaranteed precision based on multiresolution analysis and separated representations. Underpinning the numerical capabilities is a powerful petascale parallel programming environment that aims to increase both programmer productivity and code scalability. This paper describes the features and capabilities of MADNESS and briefly discusses some current applications in chemistry and several areas of physics

Understanding and application of daptomycin-susceptible dose-dependent category for Enterococcus: A mixed-methods study

Background: In 2018, the Clinical Microbiology Laboratory at our institution adopted updated daptomycin Methods: This mixed-methods study combined a clinician survey with a retrospective pre-post prescribing analysis. An 8-question survey was distributed to infectious diseases (ID) and internal medicine (IM) clinicians. A retrospective chart review of hospitalized adults with infections due to Results: Survey response rates were 40 of 98 (41%) for IM and 22 of 34 (65%) for ID clinicians. ID clinicians scored significantly higher than IM clinicians in knowledge of SDD. Chart review of 474 patients (225 pre- vs 249 post-SDD) showed that daptomycin dosage following susceptibility testing was significantly higher post-SDD compared with pre-SDD (8.5 mg/kg vs 6.4 mg/kg; Conclusions: The survey revealed that ID clinicians placed more importance on and had more confidence in the SDD category over IM clinicians. SDD reporting was associated with a change in definitive daptomycin dosing. ID specialist involvement is recommended in the care of infections due to enterococci for which daptomycin is reported as SDD given their expertise

Probabilistic chemotherapy in knee and hip replacement infection: the place of linezolid

Prosthetic joint infection (PJI) can occur with a wide range of microorganisms and clinical features. After replacement surgery of prosthetic joint, prescription of probabilistic broad-spectrum antimicrobial therapy is usual, while awaiting microbial culture results. The aim of our study was to describe the antibiotic susceptibility of microorganisms isolated from hip and knee PJI. The data were collected to determine the best alternative to the usual combination of piperacillin-tazobactam (TZP) or cefotaxime (CTX) and vancomycin (VAN). Based on a French prospective, multicenter study, we analyzed microbiological susceptibility to antibiotics of 183 strains isolated from patients with confirmed hip or knee PJI. In vitro susceptibility was evaluated: TZP+VAN, TZP+linezolid (LZD), CTX+VAN, and CTX+LZD. We also analyzed resistance to different antibiotics commonly used as oral alternatives. Among the 183 patients with PJI, 62 (34%) had a total knee prosthesis, and 121 (66%) a hip prosthesis. The main identified bacteria were Staphylococcus aureus (32.2% of isolates), coagulase-negative staphylococci (27.3%), Enterobacteriaceae (14.2%), and Streptococcus (13.7%). Infections were polymicrobial for 28 (15.3%) patients. All combinations were highly effective: CTX+VAN, CTX+LZD, TZP+VAN, and TZP+LZD (93.4%, 94%, 98.4%, and 98.9% of all cases respectively). Use of LZD instead of VAN in combination with a broad-spectrum beta-lactam covers almost all of the bacteria isolated in PJI. This association should be considered in probabilistic chemotherapy, as it is particularly easy to use (oral administration and no vancomycin monitoring)

Multicentre prospective evaluation of histological and molecular criterion for diagnosis of prosthetic-joint infection

Objectives: This multicenter prospective study was performed to assess the contribution of broad range PCR diagnosis in prosthetic-joint infection (PJI). Methods: Adult patients treated for PJI at 7 centers were included between December 2010 and March 2012. Six per-operative samples were obtained for each patient, 5 for conventional cultures and 16S rRNA gene real-time PCR followed by sequencing, and 1 for histopathological classification according to Morawietz. Cultures and PCR were performed in a highly standardized manner, with 3 quality controls of PCR analyses. An infection was considered as proved (3 criteria: per-operative, bacteriological and histological), probable (clinical or bacteriological criterium), or excluded (no criterium). Molecular criterium for predicting PJI was determined using the bacteriological one as reference (>=1 positive sample for virulent organism, and >=3 positive samples for coagulase-negative staphylococci (CoNS) and P. acnes). Results: 299 patients were included, 264 with suspicion of sepsis (S) and 35 as controls (C). The 264 S presented with acute (19%), or chronic suspicion of PJI (81%). Infection was proved or probable in 212/264 S (80%), with the bacteriological criterium in 189/212 S (89%). Out of these, 156 (83%) had monomicrobial and 33 (17%) polymicrobial infections. The isolated pathogens were S. aureus (40%), CoNS (25%), streptococci (14%), Gram-Negative rods (10%), and anaerobes 8%. Histology results were not available for 55 patients, leaving 244 patients available for analysis. Histological findings of infection (Morawietz types II or III) were present in 128/169 (76%) proved or probable infections, in 3 patients without any other criterium, and were absent in excluded infections (n=42) and controls (n=29). PCR results were not analysable for 32 patients (S=28, C=4), leaving 267 patients (S=236, C=31) available for analysis. Molecular criterium of infection was present in 63/68 (93%) proved infections, 83/124 (67%) probable infections, 3/42 excluded infections, 0/2 histological criterium alone and 2/31 controls. Molecular criterium of infection was absent in 34/189 (18%) culture-positive S, and present in 8/23 culture-negative S (8 patients treated with antibiotics). Conclusions: According to this multicenter prospective study, 16S rRNA gene real-time PCR is less susceptible than culture for diagnosis of PJI. Molecular analysis could be recommended in culture-negative patients who were receiving antibiotics

Evaluation of 16S rRNA gene PCR sensitivity and specificity for diagnosis of prosthetic joint infection: a prospective multicenter cross-sectional study

There is no standard method for the diagnosis of prosthetic joint infection (PJI). The contribution of 16S rRNA gene PCR sequencing on a routine basis remains to be defined. We performed a prospective multicenter study to assess the contributions of 16S rRNA gene assays in PJI diagnosis. Over a 2-year period, all patients suspected to have PJIs and a few uninfected patients undergoing primary arthroplasty (control group) were included. Five perioperative samples per patient were collected for culture and 16S rRNA gene PCR sequencing and one for histological examination. Three multicenter quality control assays were performed with both DNA extracts and crushed samples. The diagnosis of PJI was based on clinical, bacteriological, and histological criteria, according to Infectious Diseases Society of America guidelines. A molecular diagnosis was modeled on the bacteriological criterion (≥ 1 positive sample for strict pathogens and ≥ 2 for commensal skin flora). Molecular data were analyzed according to the diagnosis of PJI. Between December 2010 and March 2012, 264 suspected cases of PJI and 35 control cases were included. PJI was confirmed in 215/264 suspected cases, 192 (89%) with a bacteriological criterion. The PJIs were monomicrobial (163 cases [85%]; staphylococci, n = 108; streptococci, n = 22; Gram-negative bacilli, n = 16; anaerobes, n = 13; others, n = 4) or polymicrobial (29 cases [15%]). The molecular diagnosis was positive in 151/215 confirmed cases of PJI (143 cases with bacteriological PJI documentation and 8 treated cases without bacteriological documentation) and in 2/49 cases without confirmed PJI (sensitivity, 73.3%; specificity, 95.5%). The 16S rRNA gene PCR assay showed a lack of sensitivity in the diagnosis of PJI on a multicenter routine basis

Evaluation of bacteriophage as an adjunct therapy for treatment of peri-prosthetic joint infection caused by Staphylococcus aureus

Phage therapy offers a potential alternate strategy for the treatment of peri-prosthetic joint infection (PJI), particularly where limited effective antibiotics are available. We undertook preclinical trials to investigate the therapeutic efficacy of a phage cocktail, alone and in combination with vancomycin, to reduce bacterial numbers within the infected joint using a clinically-relevant model of Staphylococcus aureus-induced PJI. Infected animals were randomised to 4 treatment groups, with treatment commencing 21-days post-surgery: bacteriophage alone, vancomycin alone, bacteriophage and vancomycin, and sham. At day 28 post-surgery, animals were euthanised for microbiological and immunological assessment of implanted joints. Treatment with phage alone or vancomycin alone, led to 5-fold and 6.2-fold reductions, respectively in bacterial load within peri-implant tissue compared to shamtreated animals. Compared to sham-treated animals, a 22.5-fold reduction in S. aureus burden was observed within joint tissue of animals that were administered phage in combination with vancomycin, corresponding with decreased swelling in the implanted knee. Microbiological data were supported by evidence of decreased inflammation within the joints of animals administered phage in combination with vancomycin, compared to sham-treated animals. Our findings provide further support for phage therapy as a tolerable and effective adjunct treatment for PJI

Can air pollution affect tear film stability? a cross-sectional study in the aftermath of an explosion accident

<p>Abstract</p> <p>Background</p> <p>After an explosion and fire in two tanks containing contaminated oil and sulphur products in a Norwegian industrial harbour in 2007, the surrounding area was polluted. This caused an intense smell, lasting until the waste was removed two years later. The present study reports examinations of tear film break up time among the population. The examinations were carried out because many of the people in the area complained of sore eyes. The purpose of the study was to assess the relationship between living or working close to the polluted area and tear film stability one and a half years after the explosion.</p> <p>Methods</p> <p>All persons working or living in an area less than six kilometres from the explosion site were invited to take part in the study together with a similar number of persons matched for age and gender living more than 20 kilometres away. Three groups were established: workers in the explosion area and inhabitants near the explosion area (but not working there) were considered to have been exposed, and inhabitants far away (who did not work in the explosion area) were considered to be unexposed. A total of 734 people were examined, and the response rate was 76 percent. Tear film stability was studied by assessing non-invasive break-up time (NIBUT) using ocular microscopy. In addition Self-reported Break Up Time (SBUT) was assessed by recording the time the subject could keep his or hers eyes open without blinking when watching a fixed point on a wall. Background information was obtained using a questionnaire. Non-parametric Wilcoxon-Mann-Whitney-tests with exact p-values and multiple logistic regression analyses were performed.</p> <p>Results</p> <p>Both NIBUT and SBUT were shorter among the male exposed workers than among the inhabitants both near and far away from the explosion area. This was also found for SBUT among males in a multiple logistic regression analysis, adjusting for age and smoking.</p> <p>Conclusions</p> <p>Reduced tear film stability was found among workers in an area where an explosion accident had occurred.</p