In vitro effect of synovial fluid from patients undergoing arthroplasty surgery on MRSA biofilm formation.

BACKGROUND: Bacterial biofilm is a key component in the pathogenesis of prosthetic joint infection (PJI). Synovial fluid has been shown to have inhibitory activity against planktonic bacteria. However, the contribution of synovial fluid in prevention of Staphylococcus aureus (including MRSA) planktonic and biofilm forms is unknown. OBJECTIVES: To test the antibacterial and antibiofilm activities of synovial fluid, including that containing cefazolin, against MSSA and MRSA. MATERIALS AND METHODS: We determined the antiplanktonic and antibiofilm activities of synovial fluid collected from patients given preoperative cefazolin while undergoing elective arthroplasty surgery. MICs of cefazolin were determined for planktonic and biofilm cultures of biofilm-forming strains of MSSA and MRSA. RESULTS: Synovial fluid inhibited planktonic and biofilm cultures of MSSA and MRSA. Cefazolin-containing synovial fluid had greater antibacterial and antibiofilm activities than the same cefazolin concentration in glucose LB (GLB) broth. MSSA and MRSA MICs of cefazolin suspended in synovial fluid were 0.7 mg/L. The MICs of cefazolin diluted in GLB broth were higher, measuring 1.4 mg/L for MSSA and 23 mg/L for MRSA. CONCLUSIONS: Synovial fluid containing cefazolin inhibited biofilm- and planktonic-state MRSA cultures. This may explain the apparent effect of cefazolin in the prevention of MRSA PJI.

A systematic review on the health outcomes associated with non-endocarditis manifestations of chronic Q fever.

The aim of this study was to systematically review the non-endocarditis manifestations of chronic Q fever and understand the significance of non-specific symptoms like pain and fatigue in chronic endovascular, osteomyelitis and abscess due to chronic Q fever. We performed a systematic review using Pub Med (the National Library of Medicine (NLM)) and Scopus databases. All studies in English on chronic Q fever that listed clinical manifestations other than infective endocarditis (IE) and chronic fatigue syndrome (CFS). Meta-analysis was carried out to investigate the effects of patient's health outcomes (pain, fatigue, the need for surgery and mortality) on vascular infections, osteomyelitis and abscess. Among cases not presenting as IE or CFS, vascular infections and osteomyelitis were the most common chronic Q fever disease manifestations. There were distinct regional patterns of disease. Compared with infective endocarditis, these are significantly associated with increased risk of pain: osteomyelitis (relative risk (RR) = 4.13, 95% confidence interval (CI) 3.36-5.07), abscess (RR = 3.59, 95% CI 3.28-3.93) and vascular infection (RR = 2.46, 95% CI 1.99-3.03). The strongest significant association was observed between osteomyelitis and pain. There was no significant association between fatigue and these manifestations. Clinicians have to be aware of uncommon manifestations of chronic Q fever as they present with non-specific symptoms and are significantly associated with increased risk of morbidity and mortality. The findings emphasise the need to investigate patients with positive chronic Q fever serology presenting with acute or chronic pain for possible underlying complications.

The spatio-temporal epidemic dynamics of COVID-19 outbreak in Africa.

Corona virus disease 2019 (COVID-19), caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was first detected in the city of Wuhan, China in December 2019. Although, the disease appeared in Africa later than other regions, it has now spread to virtually all countries on the continent. We provide early spatio-temporal dynamics of COVID-19 within the first 62 days of the disease's appearance on the African continent. We used a two-parameter hurdle Poisson model to simultaneously analyse the zero counts and the frequency of occurrence. We investigate the effects of important healthcare capacities including hospital beds and number of medical doctors in different countries. The results show that cases of the pandemic vary geographically across Africa with notably high incidence in neighbouring countries particularly in West and North Africa. The burden of the disease (per 100 000) mostly impacted Djibouti, Tunisia, Morocco and Algeria. Temporally, during the first 4 weeks, the burden was highest in Senegal, Egypt and Mauritania, but by mid-April it shifted to Somalia, Chad, Guinea, Tanzania, Gabon, Sudan and Zimbabwe. Currently, Namibia, Angola, South Sudan, Burundi and Uganda have the least burden. These findings could be useful in guiding epidemiological interventions and the allocation of scarce resources based on heterogeneity of the disease patterns.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

OBJECTIVE: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. STUDY SELECTION: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. DATA SOURCES: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. DATA EXTRACTION: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. DATA SYNTHESIS: Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). CONCLUSIONS: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

Renal allograft re-use and herpetic re-infection.

A middle-aged man received a kidney transplant from a deceased multi-organ donor. The recipient suffered cardiac arrest several days post-operatively and sustained hypoxic brain injury and was declared brain dead. Following the family's consent, the allograft kidney was retrieved and re-transplanted into a man with end-stage renal failure secondary to reflux nephropathy. The liver was not transplanted due to suspicion of fatty changes based on macroscopic appearance. After transplantation of other organs, liver histology revealed coagulative parenchymal necrosis with nuclear inclusions and moderate parenchymal cholestasis, suggestive of herpes viral hepatitis. Renal implantation biopsy showed histiocytes with enlarged nuclei containing viral inclusions in the capsular fibrous tissue, with positive immunostaining for herpes simplex virus (HSV). Anti-viral therapy was commenced immediately after obtaining histological evidence of donor HSV infection. Our recipient had pre-formed immunoglobulin G antibodies to HSV-1 and HSV-2, and was immunoglobulin M negative pre-transplant. HSV viraemia was detected day 5 post-transplant with a viral load of 7688 copies/mL by polymerase chain reaction assay. The recipient completed a 30 day course of intravenous ganciclovir before switching to oral valganciclovir as standard cytomegalovirus prophylaxis. The HSV polymerase chain reaction became undetectable on day 7 of intravenous ganciclovir and has remained undetectable. The patient remains well 9 months post-transplant with an estimated glomerular filtration rate of 61 mL/min per 1.73 m(2). Although renal allograft re-use has been shown to be technically possible with a good outcome in this recipient, this does raise issues including assessment of allografts that have undergone repeated severe ischaemic insults and the potential of transmission of infections.

Activation of the lectin pathway of complement in experimental human keratitis with Pseudomonas aeruginosa.

PURPOSE: Pseudomonas aeruginosa (P. aeruginosa) microbial keratitis (MK) is a sight-threatening disease. Previous animal studies have identified an important contribution of the complement system to the clearance of P. aeruginosa infection of the cornea. Mannose-binding lectin (MBL), a pattern recognition receptor of the lectin pathway of complement, has been implicated in the host defense against P. aeruginosa. However, studies addressing the role of the lectin pathway in P. aeruginosa MK are lacking. Hence, we sought to determine the activity of the lectin pathway in human MK caused by P. aeruginosa. METHODS: Primary human corneal epithelial cells (HCECs) from cadaveric donors were exposed to two different P. aeruginosa strains. Gene expression of interleukin (IL)-6, IL-8, MBL, and other complement proteins was determined by reverse transcription-polymerase chain reaction (RT-PCR) and MBL synthesis by enzyme-linked immunosorbent assay and intracellular flow cytometry. RESULTS: MBL gene expression was not detected in unchallenged HCECs. Exposure of HCECs to P. aeruginosa resulted in rapid induction of the transcriptional expression of MBL, IL-6, and IL-8. In addition, expression of several complement proteins of the classical and lectin pathways, but not the alternative pathway, were upregulated after 5 h of challenge, including MBL-associated serine protease 1. However, MBL protein secretion was not detectable 18 h after challenge with P. aeruginosa. CONCLUSIONS: MK due to P. aeruginosa triggers activation of MBL and the lectin pathway of complement. However, the physiologic relevance of this finding is unclear, as corresponding MBL oligomer production was not observed.

TB incidence and characteristics in the remote gulf province of Papua New Guinea: a prospective study.

BACKGROUND: The incidence and characteristics of tuberculosis (TB) in remote areas of Papua New Guinea (PNG) are largely unknown. The purpose of our study was to determine the incidence of TB in the Gulf Province of PNG and describe disease characteristics, co-morbidities and drug resistance profiles that could impact on disease outcomes and transmission. METHODS: Between March 2012 and June 2012, we prospectively collected data on 274 patients presenting to Kikori Hospital with a presumptive diagnosis of TB, and on hospital inpatients receiving TB treatment during the study period. Sputum was collected for microscopy, GeneXpert analysis, culture and genotyping of isolates. RESULTS: We estimate the incidence of TB in Kikori to be 1290 per 100,000 people (95% CI 1140 to 1460) in 2012. The proportion of TB patients co-infected with HIV was 1.9%. Three of 32 TB cases tested were rifampicin resistant. Typing of nine isolates demonstrated allelic diversity and most were related to Beijing strains. CONCLUSIONS: The incidence of TB in Kikori is one of the highest in the world and it is not driven by HIV co-infection. The high incidence and the presence of rifampicin resistant warrant urgent attention to mitigate substantial morbidity in the region.

Effect of Savirin or Ticagrelor Treatment on the Expression of Commonly Used Reference Genes in Staphylococcus aureus.

Reference genes are frequently used for the normalization of quantitative reverse transcriptase PCR (qRTPCR) data in gene expression studies. Staphylococcus aureus is one of the most common causes of biofilm-related infections. Savirin and ticagrelor show in vitro as well as in vivo antibiofilm activity against S. aureus. The main aim of this study was to identify the most stably expressed reference genes to study the effect of these molecules on genes in a strong biofilm producing S. aureus isolate isolated from biofilm-related infection. Quantitative real-time PCR was performed by using relative quantification method. Four different algorithms, delta Ct, normfinder, bestkeeper, and genorm, followed by a comprehensive analysis was used to identify the most stable reference genes from a list of sixteen different candidate reference genes. All four algorithms reported different results, with some comparable findings among some methods. In the comprehensive analysis of the results of all the algorithms used, the most stable reference genes found were spa, rpoD, and pyk for savirin treatment experiment and gapdH, gyrA, and gmk for ticagrelor treatment experiment. The optimal number of reference genes required was two for both the experimental conditions. Despite having some drawbacks, each algorithm can reliably determine an appropriate reference gene independently. However, based on consensus ranking and the required optimal number of reference genes reported, spa and rpoD were the most appropriate reference genes for savirin treatment experiment, and gapdH and gyrA were most appropriate for ticagrelor treatment experiment. This study provides baseline data on reference genes to study the effect of savirin or ticagrelor treatment on the expression of potential reference genes in S. aureus. We recommend prior re-validation of reference genes on a case-by-case basis before they can be used.

Acetyl salicylic acid usage and mortality in critically ill patients with the systemic inflammatory response syndrome and sepsis.

OBJECTIVE: Low doses of acetyl salicylic acid, acting through 15-epi-lipoxin A4, have been shown to be anti-inflammatory in human studies. The manifold effects of acetyl salicylic acid on human physiology potentially may benefit patients with the systemic inflammatory response syndrome after sepsis or tissue trauma. We sought to determine whether acetyl salicylic acid administration at the time of development of systemic inflammatory response syndrome is associated with reduced mortality. DESIGN: Retrospective cohort study of consecutive intensive care unit admissions between April 2000 and November 2009. SETTING: Australian tertiary referral center. PATIENTS: Seven-thousand nine-hundred forty-five intensive care unit admissions examined. MEASUREMENTS AND MAIN RESULTS: The probability of in-hospital death during admissions in which individuals were identified as having systemic inflammatory response syndrome or sepsis was analyzed according to whether they were administered acetyl salicylic acid. Propensity analysis that matched all patients for their probability of being prescribed acetyl salicylic acid was undertaken. Among 5523 patients with a first episode of systemic inflammatory response syndrome, 2082 were administered acetyl salicylic acid in a 24-hr period around the time of systemic inflammatory response syndrome recognition. Propensity analysis showed a 10.9% mortality for acetyl salicylic acid users and 17.2% mortality in the propensity-matched nonusers (absolute risk difference -6.2%; 95% confidence interval -9.5% to -3.5%). Propensity matching also found that acetyl salicylic acid administration was associated with increased risk of renal injury (6.2% vs. 2.9%; absolute risk difference 13.3%; 95% confidence interval 2.5% to 5.0%). In the 970 patients with proven sepsis, acetyl salicylic acid administration was associated with a lower mortality (27.4% vs. 42.2%; absolute risk difference -14.8%; 95% confidence interval -18.9% to -8.6%) after propensity matching. This quasi-experimental study cannot establish a causal association between acetyl salicylic acid and death from systemic inflammatory response syndrome or sepsis. Unrecognized confounders may remain but numerous covariates are included in the analyses. CONCLUSIONS: Our study shows a strong association between acetyl salicylic acid and survival in intensive care unit systemic inflammatory response syndrome and sepsis patients. The effect of acetyl salicylic acid treatment on mortality of patients with systemic inflammatory response syndrome and sepsis needs to be evaluated with prospective randomized intervention studies.

Non-Antimicrobial Adjuvant Therapy Using Ticagrelor Reduced Biofilm-Related Staphylococcus aureus Prosthetic Joint Infection.

Background: Prosthetic joint infection (PJI), frequently caused by Staphylococcus aureus, leads to a significant arthroplasty failure rate. Biofilm is a crucial virulence factor of S. aureus that is intrinsic to the pathogenesis of PJI. Biofilm-related infections are recalcitrant to antibiotic treatment. Surgical and antibiotic therapy could be combined with non-antibacterial adjuvants to improve overall treatment success. Ticagrelor, a P2Y12 receptor inhibitor antiplatelet drug, is known to have anti-staphylococcal antibacterial and antibiofilm activity. However, the molecular mechanism for ticagrelor's antibiofilm activity and its efficacy in the treatment of S. aureus PJI are unknown. Methods: To study the in vitro antibacterial and antibiofilm activity of ticagrelor, broth microdilution and crystal violet staining method were used. Ticagrelor's effect on the expression of S. aureus biofilm genes (icaA, icaD, ebps, fib, eno, and agr) was studied using the relative quantification method. To test ticagrelor's in vivo efficacy to treat S. aureus PJI, mice were randomized into five groups (n = 8/group): infected femoral implants treated with ticagrelor alone; infected implants treated with cefazolin alone; infected implants treated with ticagrelor and cefazolin; infected implants treated with phosphate buffer solution (PBS)-positive controls, and sterile implants-negative controls. Ticagrelor was administered orally from day 4 to day 7 post-surgery, while cefazolin was injected intravenously on day 7. Results: Ticagrelor, alone and with selected antibiotics, showed in vitro antibacterial and antibiofilm activity against S. aureus. Strain-specific downregulation of biofilm-related genes, fib, icaD, ebps, and eno, was shown. In an animal model of biofilm-related S. aureus PJI, ticagrelor alone and combined with cefazolin significantly reduced bacterial concentrations on the implants compared with the positive control group. Ticagrelor significantly reduced bacterial dissemination to periprosthetic tissue compared with the positive controls. Conclusion: Ticagrelor adjuvant therapy reduced S. aureus PJI in an animal model. However, this study is very preliminary to make a conclusion on the clinical implication of the findings. Based on the current results, more studies are recommended to better understand its implication.

Effect of savirin in the prevention of biofilm-related Staphylococcus aureus prosthetic joint infection.

Background: Most of the arthroplasty surgery failure due to prosthetic joint infections (PJI) is caused by biofilm-associated Staphylococcus aureus. In a recent experimental study, savirin has been used to prevent and treat S. aureus skin infections in animal models. We explored the application of savirin in a PJI mouse model to determine its utility as an adjunct therapy to prevent PJI. Materials and methods: The in-vitro antibacterial and antibiofilm activity of savirin, with or without antibiotics (cefazolin, rifampicin, and vancomycin), against S. aureus were investigated using broth microdilution and crystal violet staining method, respectively. The effect of savirin treatment on the expression of the key biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr) in S. aureus was studied using quantitative reverse transcriptase polymerase chain reaction (qRTPCR). The in-vivo efficacy of savirin alone and with cefazolin to prevent S. aureus PJI was determined using a clinically relevant PJI mouse model. Mice were randomized into five groups (n = 8/group): 1) infected K-wire savirin treated group, 2) infected K-wire cefazolin treated group, 3) infected K-wire savirin plus cefazolin treated group, 4) infected K-wire PBS treated group, 5) sterile K-wire group. Savirin was administered subcutaneously immediately post-surgery and intravenous cefazolin was given on day seven. Results: Savirin inhibited planktonic and biofilm in-vitro growth of S. aureus, showed enhanced inhibitory activity when combined with antibiotics, and down-regulated the expression of key S. aureus biofilm-related genes (icaA, icaD, eno, fib, ebps, and agr). Savirin significantly reduced bacterial counts on joint implants in comparison with the PBS treated control, while savirin plus cefazolin reduced bacterial counts on both implants and peri-prosthetic tissues. Conclusion: Savirin adjuvant therapy may prevent biofilm formation and S. aureus PJI. This study gives baseline data for using savirin for the prevention as well as treatment of S. aureus PJI in future animal studies.

Longer than 2 hours to antibiotics is associated with doubling of mortality in a multinational community-acquired bacterial meningitis cohort.

To optimally define the association between time to effective antibiotic therapy and clinical outcomes in adult community-acquired bacterial meningitis. A systematic review of the literature describing the association between time to antibiotics and death or neurological impairment due to adult community-acquired bacterial meningitis was performed. A retrospective cohort, multivariable and propensity-score based analyses were performed using individual patient clinical data from Australian, Danish and United Kingdom studies. Heterogeneity of published observational study designs precluded meta-analysis of aggregate data (I2 = 90.1%, 95% CI 71.9-98.3%). Individual patient data on 659 subjects were made available for analysis. Multivariable analysis was performed on 180-362 propensity-score matched data. The risk of death (adjusted odds ratio, aOR) associated with treatment after two hours was 2.29 (95% CI 1.28-4.09) and increased substantially thereafter. Similarly, time to antibiotics of greater than three hours was associated with an increase in the occurrence of neurological impairment (aOR 1.79, 95% CI 1.03-3.14). Among patients with community-acquired bacterial meningitis, odds of mortality increase markedly when antibiotics are given later than two hours after presentation to the hospital.

A novel L-ficolin/mannose-binding lectin chimeric molecule with enhanced activity against Ebola virus.

Ebola viruses constitute a newly emerging public threat because they cause rapidly fatal hemorrhagic fevers for which no treatment exists, and they can be manipulated as bioweapons. We targeted conserved N-glycosylated carbohydrate ligands on viral envelope surfaces using novel immune therapies. Mannose-binding lectin (MBL) and L-ficolin (L-FCN) were selected because they function as opsonins and activate complement. Given that MBL has a complex quaternary structure unsuitable for large scale cost-effective production, we sought to develop a less complex chimeric fusion protein with similar ligand recognition and enhanced effector functions. We tested recombinant human MBL and three L-FCN/MBL variants that contained the MBL carbohydrate recognition domain and varying lengths of the L-FCN collagenous domain. Non-reduced chimeric proteins formed predominantly nona- and dodecameric oligomers, whereas recombinant human MBL formed octadecameric and larger oligomers. Surface plasmon resonance revealed that L-FCN/MBL76 had the highest binding affinities for N-acetylglucosamine-bovine serum albumin and mannan. The same chimeric protein displayed superior complement C4 cleavage and binding to calreticulin (cC1qR), a putative receptor for MBL. L-FCN/MBL76 reduced infection by wild type Ebola virus Zaire significantly greater than the other molecules. Tapping mode atomic force microscopy revealed that L-FCN/MBL76 was significantly less tall than the other molecules despite similar polypeptide lengths. We propose that alterations in the quaternary structure of L-FCN/MBL76 resulted in greater flexibility in the collagenous or neck region. Similarly, a more pliable molecule might enhance cooperativity between the carbohydrate recognition domains and their cognate ligands, complement activation, and calreticulin binding dynamics. L-FCN/MBL chimeric proteins should be considered as potential novel therapeutics.

Analysis of the impact of early surgery on in-hospital mortality of native valve endocarditis: use of propensity score and instrumental variable methods to adjust for treatment-selection bias.

BACKGROUND: The impact of early surgery on mortality in patients with native valve endocarditis (NVE) is unresolved. This study sought to evaluate valve surgery compared with medical therapy for NVE and to identify characteristics of patients who are most likely to benefit from early surgery. METHODS AND RESULTS: Using a prospective, multinational cohort of patients with definite NVE, the effect of early surgery on in-hospital mortality was assessed by propensity-based matching adjustment for survivor bias and by instrumental variable analysis. Patients were stratified by propensity quintile, paravalvular complications, valve perforation, systemic embolization, stroke, Staphylococcus aureus infection, and congestive heart failure. Of the 1552 patients with NVE, 720 (46%) underwent early surgery and 832 (54%) were treated with medical therapy. Compared with medical therapy, early surgery was associated with a significant reduction in mortality in the overall cohort (12.1% [87/720] versus 20.7% [172/832]) and after propensity-based matching and adjustment for survivor bias (absolute risk reduction [ARR] -5.9%, P<0.001). With a combined instrument, the instrumental-variable-adjusted ARR in mortality associated with early surgery was -11.2% (P<0.001). In subgroup analysis, surgery was found to confer a survival benefit compared with medical therapy among patients with a higher propensity for surgery (ARR -10.9% for quintiles 4 and 5, P=0.002) and those with paravalvular complications (ARR -17.3%, P<0.001), systemic embolization (ARR -12.9%, P=0.002), S aureus NVE (ARR -20.1%, P<0.001), and stroke (ARR -13%, P=0.02) but not those with valve perforation or congestive heart failure. CONCLUSIONS: Early surgery for NVE is associated with an in-hospital mortality benefit compared with medical therapy alone.

Mannose-binding lectin deficiency influences innate and antigen-presenting functions of blood myeloid dendritic cells.

Mannose-binding lectin (MBL) is a serum lectin that plays a significant role in innate host defence. Individuals with mutations in exon 1 of the MBL2 gene have reduced MBL ligand binding and complement activation function and increased incidence of infection. We proposed that, during infection, MBL deficiency may impact on dendritic cell (DC) function. We analysed the blood myeloid DC (MDC) surface phenotype, inflammatory cytokine production and antigen-presenting capacity in MBL-deficient (MBL-D) individuals and MBL-sufficient (MBL-S) individuals using whole blood culture supplemented with zymosan (Zy) or MBL-opsonized zymosan (MBL-Zy) as a model of infection. Zy-stimulated MDCs from MBL-D individuals had significantly increased production of interleukin (IL)-6 and tumour necrosis factor (TNF)-α. Stimulation with MBL-Zy significantly decreased IL-6 production by MDCs from MBL-D, but had no effect on TNF-α production. MDCs from both MBL-S and MBL-D individuals up-regulated expression of the activation molecule CD83, and down-regulated expression of homing (CXCR4), adhesion (CD62L, CD49d) and costimulatory (CD40, CD86) molecules in response to Zy and MBL-Zy. MDC from both MBL-D and MBL-S individuals induced proliferation of allogeneic (allo) T cells following Zy or MBL-Zy stimulation; however, MBL-D individuals demonstrated a reduced capacity to induce effector allo-T cells. These data indicate that MBL deficiency is associated with unique functional characteristics of pathogen-stimulated blood MDCs manifested by increased production of IL-6, combined with a poor capacity to induce effector allo-T-cell responses. In MBL-D individuals, these functional features of blood MDCs may influence their ability to mount an immune response.

Pandemic (H1N1) 2009 risk for frontline health care workers.

To determine whether frontline health care workers (HCWs) are at greater risk for contracting pandemic (H1N1) 2009 than nonclinical staff, we conducted a study of 231 HCWs and 215 controls. Overall, 79 (17.7%) of 446 had a positive antibody titer by hemagglutination inhibition, with 46 (19.9%) of 231 HCWs and 33 (15.3%) of 215 controls positive (OR 1.37, 95% confidence interval 0.84-2.22). Of 87 participants who provided a second serum sample, 1 showed a 4-fold rise in antibody titer; of 45 patients who had a nose swab sample taken during a respiratory illness, 7 had positive results. Higher numbers of children in a participant's family and working in an intensive care unit were risk factors for infection; increasing age, working at hospital 2, and wearing gloves were protective factors. This highly exposed group of frontline HCWs was no more likely to contract pandemic (H1N1) 2009 influenza infection than nonclinical staff, which suggests that personal protective measures were adequate in preventing transmission.

Mannose-binding lectin as part of the complement pathway: characterization in non-inflamed and inflamed human eyes.

BACKGROUND: Mannose-binding lectin plays a central effector role in the lectin pathway of complement activation. Frequently occurring MBL2 polymorphisms result in mannose-binding lectin deficiency, which increases susceptibility to infection. We characterized mannose-binding lectin levels and function in non-inflamed and inflamed human eyes, and evaluated its relationship to blood mannose-binding lectin levels and function. DESIGN: Prospective, observational clinical study with controls and cases. PARTICIPANTS: Twenty-seven patients with paired blood and ocular samples (aqueous and/or vitreous) including 15 controls (non-inflamed) and 12 cases (inflamed). METHODS: Blood and ocular samples were collected from controls (n = 15) with quiet eyes during elective cataract surgery and cases with inflamed eyes including proven/suspected endophthalmitis (n = 11) and herpetic retinal vasculitis (n = 1). Mannan-binding and C4 deposition enzyme-linked quantify mannose-binding lectin levels and function. MAIN OUTCOME MEASURES: Blood and ocular mannose-binding lectin levels and function. RESULTS: Of 27 patients, 10 (37%) were mannose-binding lectin-deficient (defined as blood mannose-binding lectin levels <500 ng/mL). Blood mannose-binding lectin levels (P= 0.16) or function (P= 0.43) were not significantly different between controls and cases. As expected, there was a high correlation between blood mannose-binding lectin levels and function (r(2) = 0.74). However, there was significantly more mannose-binding lectin in inflamed eyes than non-inflamed eyes measured as level (P < 0.01) or C4 deposition function (P < 0.01). CONCLUSIONS: Our study demonstrated that mannose-binding lectin is significantly elevated in inflamed human eyes but virtually undetectable in non-inflamed control eyes, suggesting a role in sight-threatening ocular inflammation.

Non-Antimicrobial Adjuvant Strategies to Tackle Biofilm-Related Staphylococcus aureus Prosthetic Joint Infections.

Staphylococcus aureus frequently causes community- and hospital-acquired infections. S. aureus attachment followed by biofilm formation on tissues and medical devices plays a significant role in the establishment of chronic infections. Staphylococcal biofilms encase bacteria in a matrix and protect the cells from antimicrobials and the immune system, resulting in infections that are highly resistant to treatment. The biology of biofilms is complex and varies between organisms. In this review, we focus our discussion on S. aureus biofilms and describe the stages of their formation. We particularly emphasize genetic and biochemical processes that may be vulnerable to novel treatment approaches. Against this background, we discuss treatment strategies that have been successful in animal models of S. aureus biofilm-related infection and consider their possible use for the prevention and eradication of biofilm-related S. aureus prosthetic joint infection.