scholarly journals Muddled mechanisms: recent progress towards antimalarial target identification

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2514 ◽  
Author(s):  
Rachel L. Edwards ◽  
Audrey R. Odom John
Keyword(s):  
High Throughput Screening ◽  
Target Identification ◽  
Control Measures ◽  
Combination Therapies ◽  
The Past ◽  
Infection Control Measures ◽  
Causative Agents ◽  
The Impact ◽  
Innovative Techniques ◽  
Potential Public Health

In the past decade, malaria rates have plummeted as a result of aggressive infection control measures and the adoption of artemisinin-based combination therapies (ACTs). However, a potential crisis looms ahead. Treatment failures to standard antimalarial regimens have been reported in Southeast Asia, and devastating consequences are expected if resistance spreads to the African continent. To prevent a potential public health emergency, the antimalarial arsenal must contain therapeutics with novel mechanisms of action (MOA). An impressive number of high-throughput screening (HTS) campaigns have since been launched, identifying thousands of compounds with activity against one of the causative agents of malaria, Plasmodium falciparum. Now begins the difficult task of target identification, for which studies are often tedious, labor intensive, and difficult to interpret. In this review, we highlight approaches that have been instrumental in tackling the challenges of target assignment and elucidation of the MOA for hit compounds. Studies that apply these innovative techniques to antimalarial target identification are described, as well as the impact of the data in the field.

scholarly journals The impact of population-wide rapid antigen testing on SARS-CoV-2 prevalence in Slovakia

Science ◽  
2021 ◽  
pp. eabf9648
Author(s):  
Martin Pavelka ◽  
Kevin Van-Zandvoort ◽  
Sam Abbott ◽  
Katharine Sherratt ◽  
Marek Majdan ◽  
...  
Keyword(s):  
Infection Control ◽  
Control Measures ◽  
Infection Control Measures ◽  
Household Members ◽  
The Impact ◽  
Antigen Testing

Slovakia conducted multiple rounds of population-wide rapid antigen testing for SARS-CoV-2 in late 2020, combined with a period of additional contact restrictions. Observed prevalence decreased by 58% (95% CI: 57-58%) within one week in the 45 counties that were subject to two rounds of mass testing, an estimate that remained robust when adjusting for multiple potential confounders. Adjusting for epidemic growth of 4.4% (1.1-6.9%) per day preceding the mass testing campaign, the estimated decrease in prevalence compared to a scenario of unmitigated growth was 70% (67-73%). Modelling indicated that this decrease could not be explained solely by infection control measures, but required the additional impact of isolation and quarantine of household members of those testing positive.

Multihospital Outbreak ofClostridium difficileRibotype 027 Infection: Epidemiology and Analysis of Control Measures

2011 ◽  
Vol 32 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Mamoon A. Aldeyab ◽  
Michael J. Devine ◽  
Peter Flanagan ◽  
Michael Mannion ◽  
Avril Craig ◽  
...  
Keyword(s):  
Infection Control ◽  
Action Plan ◽  
Essential Element ◽  
Control Measures ◽  
Environmental Hygiene ◽  
Ribotype 027 ◽  
Infection Control Measures ◽  
Health And Social Care ◽  
Large Outbreak ◽  
The Impact

Objective.To report a large outbreak ofClostridium difficileinfection (CDI; ribotype 027) between June 2007 and August 2008, describe infection control measures, and evaluate the impact of restricting the use of fluoroquinolones in controlling the outbreak.Design.Outbreak investigation in 3 acute care hospitals of the Northern Health and Social Care Trust in Northern Ireland.Interventions.Implementation of a series of CDI control measures that targeted high-risk antibiotic agents (ie, restriction of fluoroquinolones), infection control practices, and environmental hygiene.Results.A total of 318 cases of CDI were identified during the outbreak, which was the result of the interaction betweenC. difficileribotype 027 being introduced into the affected hospitals for the first time and other predisposing risk factors (ranging from host factors to suboptimal compliance with antibiotic guidelines and infection control policies). The 30-day all-cause mortality rate was 24.5%; however, CDI was the attributable cause of death for only 2.5% of the infected patients. Time series analysis showed that restricting the use of fluoroquinolones was associated with a significant reduction in the incidence of CDI (coefficient, —0.054; lag time, 4 months;P= .003).Conclusion.These findings provide additional evidence to support the value of antimicrobial stewardship as an essential element of multifaceted interventions to control CDI outbreaks. The present CDI outbreak was ended following the implementation of an action plan improving communication, antibiotic stewardship, infection control practices, environmental hygiene, and surveillance.

The Analysis of the Impact of a Mild, Low-iodine, Lotion Soap on the Reduction of Nosocomial Methicillin-Resistant Staphylococcus aureus: A New Opportunity for Surveillance by Objectives

1987 ◽  
Vol 8 (7) ◽  
pp. 284-288 ◽  
Author(s):  
Kim M. Onesko ◽  
Eugene C. Wienke
Keyword(s):  
Staphylococcus Aureus ◽  
Nosocomial Infections ◽  
Control Measures ◽  
Methicillin Resistant ◽  
Care Community ◽  
Infection Control Measures ◽  
Medical Division ◽  
Tract Infections ◽  
The Impact ◽  
Community Teaching

AbstractA significant unremitting increase in the incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) infections in a 500-bed acute care community teaching hospital prompted reevaluation of the efficacy of the infection control measures used. A well-accepted, low-iodine, antimicrobial soap was used to replace a liquid natural handsoap in two areas with the highest incidence of MRSA—the intensive care unit, and a medical division.Over a two-year period, an analysis was made of the effect of soap replacement on nosocomial infections and pathogens. Soap changeover occurred at the midpoint of the two-year period. From year to year, the nosocomial MRSA rate decreased 80% (t test, P=0.005). Other pathogens that demonstrated a dramatic decrease included methicillin-sensitive Staphylococcus aureus (MSSA), infections where no pathogens were isolated, and various gram-negative infections. Categories of nosocomial infections that decreased included surgical wound infections, primary bacteremias, and respiratory tract infections. The overall nosocomial infection rate of the two combined areas decreased 21.5%, representing a year-to-year savings of $109,500. As a result, the decision was made to install the low-iodine hand-soap permanently at all sinks within the hospital.

Control of Vancomycin-Resistant Enterococci at a Community Hospital: Efficacy of Patient and Staff Cohorting

1999 ◽  
Vol 20 (2) ◽  
pp. 106-109 ◽  
Author(s):  
Elise M. Jochimsen ◽  
Laurie Fish ◽  
Kelly Manning ◽  
Sally Young ◽  
Daniel A. Singer ◽  
...  
Keyword(s):  
Community Hospital ◽  
Point Prevalence ◽  
Control Measures ◽  
Prevalence Survey ◽  
Infection Control Measures ◽  
Contact Isolation ◽  
Point Prevalence Survey ◽  
Vancomycin Resistant Enterococci ◽  
Vancomycin Resistant ◽  
The Impact

AbstractObjective:To evaluate the efficacy of patient and staff cohorting to control vancomycin-resistant enterococci (VRE) at an Indianapolis community hospital.Design:To interrupt transmission of VRE, a VRE point-prevalence survey of hospital inpatients was conducted, and VRE-infected or -colonized patients were cohorted on a single ward with dedicated nursing staff and patient-care equipment. To assess the impact of the intervention, staff compliance with contact isolation procedures was observed, and the VRE point-prevalence survey was repeated 2 months after the cohort ward was established.Results:Following the establishment of the cohort ward, VRE prevalence among all hospitalized inpatients decreased from 8.1% to 4.7% (25 positive cultures among 310 patients compared to 13 positive cultures among 276 patients,P=.14); VRE prevalence among patients whose VRE status was unknown before cultures were obtained decreased from 5.9% to 0.8% (18 positive cultures among 303 patients compared to 2 positive cultures among 262 patients,P=.002); and observed staff-patient interactions compliant with published isolation recommendations increased (5 [22%] of 23 interactions compared to 36 [88%] of 41 interactions,P<.0001).Conclusions:Our data suggest that, in hospitals with endemic VRE or continued VRE transmission despite implementation of contact isolation measures, establishing a VRE cohort ward may be a practical and effective method to improve compliance with infection control measures and thereby to control epidemic or endemic VRE transmission.

Skin as a Source of Nosocomial Infection: Directions for Future Research

1986 ◽  
Vol 7 (S2) ◽  
pp. 113-117 ◽  
Author(s):  
Dennis G. Maki
Keyword(s):  
Clinical Trials ◽  
Nosocomial Infection ◽  
Scientific Data ◽  
Control Measures ◽  
Future Research ◽  
Controlled Clinical Trials ◽  
Nosocomial Pathogens ◽  
The Past ◽  
Infection Control Measures ◽  
Per Se

Whereas infections of the skin per se comprise only a fraction of all institutionally-acquired infections, the skin has become one of the most important reservoirs of nosocomial pathogens in the hospital. Professor Noble has provided a scholarly review of the increasing importance of the major constituents of the cutaneous microflora as nosocomial pathogens and what we know of their epidemiology. Unfortunately, the empiricism and limited scientific data which underlie essential infection control measures in this area, particularly in regard to cutaneous antisepsis and handwashing, is almost incongruous in an era in which controlled clinical trials have dominated most other areas of medicine. The numerous outbreaks traced to contaminated antiseptics and disinfectants over the past two decades, stand as mute testimony to the inadequate investigative attention this area has received.

scholarly journals Tackling resistance: emerging antimalarials and new parasite targets in the era of elimination

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1170 ◽  
Author(s):  
Emily S. Mathews ◽  
Audrey R. Odom John
Keyword(s):  
Drug Resistance ◽  
Malaria Elimination ◽  
Large Scale ◽  
Therapeutic Targets ◽  
Control Measures ◽  
Multi Drug Resistance ◽  
Development Projects ◽  
Combination Therapies ◽  
The Past ◽  
Antimalarial Compounds

Malaria remains a significant contributor to global human mortality, and roughly half the world’s population is at risk for infection with Plasmodium spp. parasites. Aggressive control measures have reduced the global prevalence of malaria significantly over the past decade. However, resistance to available antimalarials continues to spread, including resistance to the widely used artemisinin-based combination therapies. Novel antimalarial compounds and therapeutic targets are greatly needed. This review will briefly discuss several promising current antimalarial development projects, including artefenomel, ferroquine, cipargamin, SJ733, KAF156, MMV048, and tafenoquine. In addition, we describe recent large-scale genetic and resistance screens that have been instrumental in target discovery. Finally, we highlight new antimalarial targets, which include essential transporters and proteases. These emerging antimalarial compounds and therapeutic targets have the potential to overcome multi-drug resistance in ongoing efforts toward malaria elimination.

scholarly journals Retrospective Study on Personal Protective Equipment During Pandemic Link to Outbreak of Carbpenem-Resistant Enterobacteriace

2021 ◽  
Vol 1 (S1) ◽  
pp. s9-s10
Author(s):  
Kenisha Evans ◽  
Jennifer LeRose ◽  
Angela Beatriz Cruz ◽  
Lavina Jabbo ◽  
Teena Chopra
Keyword(s):  
Retrospective Study ◽  
Infection Control ◽  
Personal Protective Equipment ◽  
Horizontal Transmission ◽  
Control Measures ◽  
Protective Equipment ◽  
Local Health ◽  
Infection Rates ◽  
Infection Control Measures ◽  
The Impact

Background: In 2019, according to the Centers for Disease Control and Prevention, carbapenem-resistant Enterobacteriaceae (CRE), had cost the lives of >35,000 patients, particularly the most virulent plasmid-mediated New Delhi metallo-β-lactamase (NDM). Although healthcare systems normally have strict surveillance and infection control measures for CRE, the rapid emergence of novel SAR-CoV-2 and COVID-19 led to a shortage of personal protective equipment (PPE) and medical supplies. As a result, routine infection practices, such as contact precautions, were violated. Studies have shown this depletion and shift in resources compromised the control of infections such CRE leading to rising horizontal transmission. Method: A retrospective study was conducted at a tertiary healthcare system in Detroit, Michigan, to determine the impact of PPE shortages during the COVID-19 pandemic on NDM infection rates. The following periods were established during 2020 based on PPE availability: (1) pre-PPE shortage (January–June), (2) PPE shortage (July–October), and (3) post-PPE shortage (November–December). Rates of NDM per 10,000 patient days were compared between periods using the Wilcoxon signed rank-sum test. Isolates were confirmed resistant by NDM by molecular typing performed by the Michigan State Health Department. Patient characteristics were gathered by medical chart review and patient interviews by telephone. Results: Overall, the average rate of NDM infections was 1.82 ±1.5 per 10,000 patient days. Rates during the PPE shortage were significantly higher, averaging 3.6 ±1.1 cases per 10,000 patient days (P = .02). During this time, several infections occurred within patients on the same unit and/or patients with same treating team, suggesting possible horizontal transmission. Once PPE stock was replenished and isolation practices were reinstated, NDM infection rates decreased to 0.77 ±1.1 per 10,000 patient days. Conclusion: Control of CRE requires strategic planning with active surveillance, antimicrobial constructs, and infection control measures. The study illustrates that in times of crisis, such as the COVID-19 pandemic, the burden of effective infection control requires much more multidisciplinary efforts to prevent unintentional lapses in patient safety. A swift response by the state and local health departments at a tertiary-care healthcare center conveyed a positive mitigation of the highest clinical threats and decreased horizontal transmission of disease.Funding: NoDisclosures: None

scholarly journals Adaptability and responsiveness: keys to operational measures in a regional hospital radiology department during the current COVID-19 pandemic

BJR|Open ◽  
2020 ◽  
Vol 2 (1) ◽  
pp. 20200017
Author(s):  
Pratik Mukherjee ◽  
Tze Chwan Lim ◽  
Ashish Chawla ◽  
Hong Chou ◽  
Wilfred C G Peh
Keyword(s):  
Disease Transmission ◽  
Healthcare Systems ◽  
Regional Hospital ◽  
Control Measures ◽  
Radiology Department ◽  
Public Healthcare ◽  
The Past ◽  
Infection Control Measures ◽  
Potential Impact ◽  
Operational Practices

The rapid and mostly uncontrolled spread of the coronavirus disease 2019 pandemic over the past 4 months has overwhelmed many healthcare systems worldwide. In Singapore, while our public healthcare institutions were considered well prepared due to our prior experience with the SARS outbreak, there was an unexpected surge of infected patients over the recent 2 months to deal with. We describe our radiology department’s experience in modifying operational practices and implementing strict infection control measures aimed at minimizing disease transmission and mitigating the potential impact of possible staff infection. From the perspective of serving a medium-sized regional hospital and limited by physical and manpower constraints, our radiology department had to adapt quickly and modify our initial responses and practices as the disease scenario changed. We have also enumerated some guidelines for planning future radiology departments.

Antimicrobial Coating of Devices for Prevention of Infection: Principles and Protection

2007 ◽  
Vol 30 (9) ◽  
pp. 820-827 ◽  
Author(s):  
R. O. Darouiche
Keyword(s):  
Antimicrobial Agents ◽  
Bacterial Colonization ◽  
Control Measures ◽  
Clinical Infection ◽  
Antimicrobial Coating ◽  
Infection Control Measures ◽  
Surgical Implants ◽  
Clinical Protection ◽  
Coating Characteristics ◽  
The Impact

Device-associated infections are responsible for about half of nosocomial infections and can cause major medical and economical sequelae. Despite adherence to basic infection control measures, which constitute the mainstay for preventing infection, infections associated with certain devices continue to exist at unacceptably high rates. Potentially-preventive, antimicrobial-utilizing strategies include systemic antibiotic prophylaxis and local administration of antimicrobial agents (antibiotics or antiseptics), which includes antimicrobial irrigation of the surgical field, placement of antimicrobial carriers, antiseptic cleansing of the skin, dipping of surgical implants in antimicrobial solutions, and inserting antimicrobial-coated implants. Since bacterial colonization of the indwelling device is a prelude to infection, prevention of device colonization may lead to a lower rate of clinical infection. Different approaches for antimicrobial coating of devices have been variably successful in preventing device-associated infections. Optimal characteristics of antimicrobial coating can help predict the likelihood and degree of clinical protection against infection. This review addresses the impact of device-related infection, antimicrobial-utilizing approaches for preventing infection, clinical protection afforded by different types of antimicrobial coating, characteristics that predict the ability of antimicrobial coating of devices to prevent clinical infection, and future directions of antimicrobial coating.

scholarly journals Stability of Screening Compounds in Wet DMSO

2008 ◽  
Vol 13 (10) ◽  
pp. 999-1006 ◽  
Author(s):  
Caroline Engeloch ◽  
Ulrich Schopfer ◽  
Ingo Muckenschnabel ◽  
Francois Le Goff ◽  
Hervé Mees ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Medicinal Chemistry ◽  
Storage Conditions ◽  
Pragmatic Approach ◽  
Analytical Quality ◽  
The Past ◽  
Effect Of Water ◽  
The Impact

The impact of storage conditions on compound stability and compound solubility has been debated intensely over the past 5 years. At Novartis, the authors decided to opt for a storage concept that can be considered controversial because they are using a DMSO/water (90/10) mixture as standard solvent. To assess the effect of water in DMSO stocks on compound stability, the authors monitored the purity of a subset of 1404 compounds from ongoing medicinal chemistry projects over several months. The study demonstrated that 85% of the compounds were stable in wet DMSO over a 2-year period at 4 °C. This result validates the storage concept developed at Novartis as a pragmatic approach that takes advantage of the benefits of DMSO/water mixtures while mediating the disadvantages. In addition, the authors describe how purity data collected over the course of the chemical validation of high-throughput screening actives are used to improve the analytical quality of the Novartis screening deck. ( Journal of Biomolecular Screening 2008:999-1006)

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