Rhesus macaques self-curing from a schistosome infection can display complete immunity to challenge

To date there is only one single drug with modest efficacy and no vaccine available to protect from schistosomiasis. Here, Amaral et al. characterize the self-cure process of rhesus macaques following primary infection and secondary challenge with Schistosoma mansoni to inform future vaccine development studies.The rhesus macaque provides a unique model of acquired immunity against schistosomes, which afflict >200 million people worldwide. By monitoring bloodstream levels of parasite-gut-derived antigen, we show that from week 10 onwards an established infection with Schistosoma mansoni is cleared in an exponential manner, eliciting resistance to reinfection. Secondary challenge at week 42 demonstrates that protection is strong in all animals and complete in some. Antibody profiles suggest that antigens mediating protection are the released products of developing schistosomula. In culture they are killed by addition of rhesus plasma, collected from week 8 post-infection onwards, and even more efficiently with post-challenge plasma. Furthermore, cultured schistosomula lose chromatin activating marks at the transcription start site of genes related to worm development and show decreased expression of genes related to lysosomes and lytic vacuoles involved with autophagy. Overall, our results indicate that enhanced antibody responses against the challenge migrating larvae mediate the naturally acquired protective immunity and will inform the route to an effective vaccine.Cancer Signaling networks and Molecular Therapeutic

Application of minimal important differences in degenerative knee disease outcomes:A systematic review and case study to inform BMJ Rapid Recommendations

Objectives: To identify the most credible anchor-based minimal important differences (MIDs) for patient important outcomes in patients with degenerative knee disease, and to inform BMJ Rapid Recommendations for arthroscopic surgery versus conservative management Design: Systematic review. Outcome measures: Estimates of anchor-based MIDs, and their credibility, for knee symptoms and health-related quality of life (HRQoL). Data sources: MEDLINE, EMBASE and PsycINFO. Eligibility criteria: We included original studies documenting the development of anchor-based MIDs for patient-reported outcomes (PROs) reported in randomised controlled trials included in the linked systematic review and meta-analysis and judged by the parallel BMJ Rapid Recommendations panel as critically important for informing their recommendation: measures of pain, function and HRQoL. Results: 13 studies reported 95 empirically estimated anchor-based MIDs for 8 PRO instruments and/or their subdomains that measure knee pain, function or HRQoL. All studies used a transition rating (global rating of change) as the anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found wide variation in MID values. Many studies suffered from serious methodological limitations. We identified the following most credible MIDs: Western Ontario and McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15). Conclusions: We were able to distinguish between more and less credible MID estimates and provide best estimates for key instruments that informed evidence presentation in the associated systematic review and judgements made by the Rapid Recommendation panel.Canadian Institutes of Health Research DC0190SR Australian National Health and Medical Research Council (NHMRC

International Nosocomial Infection Control Consortium report, data summary of 50 countries for 2010-2015: Device-associated module

•We report INICC device-associated module data of 50 countries from 2010-2015.•We collected prospective data from 861,284 patients in 703 ICUs for 3,506,562 days.•DA-HAI rates and bacterial resistance were higher in the INICC ICUs than in CDC-NHSN's.•Device utilization ratio in the INICC ICUs was similar to CDC-NHSN's. Background: We report the results of International Nosocomial Infection Control Consortium (INICC) surveillance study from January 2010-December 2015 in 703 intensive care units (ICUs) in Latin America, Europe, Eastern Mediterranean, Southeast Asia, and Western Pacific. Methods: During the 6-year study period, using Centers for Disease Control and Prevention National Healthcare Safety Network (CDC-NHSN) definitions for device-associated health care-associated infection (DA-HAI), we collected prospective data from 861,284 patients hospitalized in INICC hospital ICUs for an aggregate of 3,506,562 days. Results: Although device use in INICC ICUs was similar to that reported from CDC-NHSN ICUs, DA-HAI rates were higher in the INICC ICUs: in the INICC medical-surgical ICUs, the pooled rate of central line-associated bloodstream infection, 4.1 per 1,000 central line-days, was nearly 5-fold higher than the 0.8 per 1,000 central line-days reported from comparable US ICUs, the overall rate of ventilator-associated pneumonia was also higher, 13.1 versus 0.9 per 1,000 ventilator-days, as was the rate of catheter-associated urinary tract infection, 5.07 versus 1.7 per 1,000 catheter-days. From blood cultures samples, frequencies of resistance of Pseudomonas isolates to amikacin (29.87% vs 10%) and to imipenem (44.3% vs 26.1%), and of Klebsiella pneumoniae isolates to ceftazidime (73.2% vs 28.8%) and to imipenem (43.27% vs 12.8%) were also higher in the INICC ICUs compared with CDC-NHSN ICUs. Conclusions: Although DA-HAIs in INICC ICU patients continue to be higher than the rates reported in CDC-NSHN ICUs representing the developed world, we have observed a significant trend toward the reduction of DA-HAI rates in INICC ICUs as shown in each international report. It is INICC's main goal to continue facilitating education, training, and basic and cost-effective tools and resources, such as standardized forms and an online platform, to tackle this problem effectively and systematically