Salmonellae are gram-negative bacteria that cause gastroenteritis and enteric fever. Salmonella virulence requires the coordinated expression of complex arrays of virulence factors that allow the bacterium to evade the host's immune system. All Salmonella serotypes share the ability to invade the host by inducing their own uptake into cells of the intestinal epithelium. In addition, Salmonella serotypes associated with gastroenteritis orchestrate an intestinal inflammatory and secretory response, whereas serotypes that cause enteric fever establish systemic infection through their ability to survive and replicate in mononuclear phagocytes. This review explores the molecular basis of selected Salmonella virulence strategies, with an emphasis on general themes of bacterial pathogenesis as exemplified by Salmonella.
Vaccination of A. nancymai with yMSP1(19) induced protective immune responses. The course of recrudescing parasitemias in protected monkeys suggested that immunity is not mediated by antibodies that block invasion. Our data indicate that vaccine trials with the highly adapted FVO strain of P. falciparum can be tested in A. nancymai and that MSP1(19) is a promising anti-blood-stage vaccine for human trials.
Among US veterans, ST131, primarily its H30 subclone, accounts for most antimicrobial-resistant E. coli and is the dominant E. coli strain overall. Possible contributors include multidrug resistance, extensive virulence gene content, and ongoing transmission. Focused attention to ST131, especially its H30 subclone, could reduce infection-related morbidity, mortality, and costs among veterans.
The Salmonella enterica serovar Typhimurium type III secretion system (TTSS) encoded in Salmonella pathogenicity island 2 (SPI-2) promotes replication within host cells and systemic infection of mice. The SPI-2 TTSS is expressed following Salmonella internalization into host cells and translocates effectors across the membrane of the Salmonella-containing vacuole (SCV). Two effectors with similar amino-terminal domains, SseJ and SifB, localize to the SCV membrane in infected HEp-2 cells and subsequently traffic away from the SCV along Salmonella-induced-filaments (Sifs). Following infection of RAW cells, SseJ and SifB localize to the SCV as well as LAMP-1-positive, vesicular-appearing structures distant from the SCV. Trafficking of SseJ and SifB away from the SCV requires the SPI-2 effector SifA. Deletion of sseJ, but not sifB, leads to attenuation of Salmonella replication in mice following intraperitoneal inoculation. The contribution of SseJ to in vivo replication is identical in wild-type and sifA deletion backgrounds, suggesting that SseJ trafficking away from the SCV along Sifs is unnecessary for its virulence function.
Administrative code data (ACD), such as International Classifications of Diseases, Ninth Revision, Clinical Modification codes, are widely used in surveillance and public reporting programs that seek to identify healthcare-associated infections (HAIs); however, little is known about their accuracy. This systematic review summarizes evidence for the accuracy of ACD for the detection of selected HAIs, including catheter-associated urinary tract infection, Clostridium difficile infection (CDI), central line-associated bloodstream infection, ventilator-associated pneumonia/events, postprocedure pneumonia, methicillin-resistant Staphylococcus aureus, and surgical site infections (SSIs). We conducted meta-analysis for SSIs and CDIs, where acceptable numbers of primary studies were available. For these 2 conditions, ACD have moderate sensitivity and high specificity, but evidence for detection of other HAIs is limited. With current low prevalence of HAIs, the positive predictive value of ACD algorithms would be low. ACD may be inaccurate for detection of many HAIs and should be used cautiously for surveillance and reporting purposes.
Background Access to human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is often poor in small urban and rural areas because of stigma and long distances to providers. The Iowa Department of Public Health and The University of Iowa created a regional telehealth program to address these barriers (“Iowa TelePrEP”). We describe initial TelePrEP results and share lessons learned. Methods Iowa Department of Public Health personnel in sexually transmitted infection (STI) clinics, disease intervention specialist and partner services, and HIV testing programs referred clients to pharmacists at University of Iowa. Clients could also self-refer via a website. Pharmacists completed video visits with clients in the community on smartphones and other devices, arranged local laboratory studies, and mailed medications. We performed a retrospective record review to quantify rates of PrEP referral, initiation, retention, guideline-concordant laboratory monitoring, and STI identification and treatment. Results Between February 2017 and October 2018, TelePrEP received 186 referrals (37% from public health) and completed 127 (68%) initial video visits with clients. Median client age was 32; 91% were men who have sex with men. Most clients with video visits (91%) started PrEP. Retention in TelePrEP at 6 months was 61%, and 96% of indicated laboratory monitoring tests were completed. Screening identified 37 STIs (8 syphilis, 10 gonorrhea, 19 chlamydia). Disease intervention specialist and partner services linked all clients with STIs to local treatment within 14 days (80% in 3 days). Conclusions Using widely available technology and infrastructure, public health departments and health care systems can collaborate to develop regional telehealth programs to deliver PrEP in small urban and rural settings.
Many studies have evaluated bundled interventions to improve hand hygiene compliance. However, there are few evidence-based recommendations on optimal interventions for implementation. We aimed to systematically review all studies on interventions to improve hand hygiene compliance to evaluate existing bundles and identify areas of promise to target high-quality studies. Adjusted risk ratios were pooled to assess common bundles. Of the 8148 studies evaluated, 6 randomized controlled trials and 39 quasi-experimental studies met inclusion criteria. Three studies evaluated the interventions education, reminders, feedback, administrative support, and access to alcohol-based hand rub as a bundle, which was associated with improved hand hygiene compliance (pooled odds ratio [OR], 1.82; 95% confidence interval [CI], 1.69-1.97). Another bundle of education, reminders, and feedback evaluated in 3 studies was associated with improved compliance (pooled OR, 1.47; 95% CI, 1.12-1.94). These bundles should be further studied using high-quality study designs and compared with other interventions.
IMPORTANCE Randomized clinical trials have yielded conflicting results about the effects of remdesivir therapy on survival and length of hospital stay among people with COVID-19. OBJECTIVE To examine associations between remdesivir treatment and survival and length of hospital stay among people hospitalized with COVID-19 in routine care settings. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used data from the Veterans Health Administration (VHA) to identify adult patients in 123 VHA hospitals who had a first hospitalization with laboratory-confirmed COVID-19 from May 1 to October 8, 2020. Propensity score matching of patients initiating remdesivir treatment to control patients who had not initiated remdesivir treatment by the same hospital day was used to create the analytic cohort. EXPOSURES Remdesivir treatment. MAIN OUTCOMES AND MEASURES Time to death within 30 days of remdesivir treatment initiation (or corresponding hospital day for matched control individuals) and time to hospital discharge with time to death as a competing event. Associations between remdesivir treatment and these outcomes were assessed using Cox proportional hazards regression in the matched cohort.RESULTS The initial cohort included 5898 patients admitted to 123 hospitals, 2374 (40.3%) of whom received remdesivir treatment (2238 men [94.3%]; mean [SD] age, 67.8 [12.8] years) and 3524 (59.7%) of whom never received remdesivir treatment (3302 men [93.7%]; mean [SD] age, 67.0 [14.4] years). After propensity score matching, the analysis included 1172 remdesivir recipients and 1172 controls, for a final matched cohort of 2344 individuals. Remdesivir recipients and matched controls were similar with regard to age (mean [SD], 66.6 [14.2] years vs 67.5 [14.1] years), sex (1101 men [93.9%] vs 1101 men [93.9%]), dexamethasone use (559 [47.7%] vs 559 [47.7%]), admission to the intensive care unit (242 [20.7%] vs 234 [19.1%]), and mechanical ventilation use (69 [5.9%] vs 45 [3.8%]). Standardized differences were less than 10% for all measures. Remdesivir treatment was not associated with 30-day mortality (143 remdesivir recipients [12.2%] vs 124 controls [10.6%]; log rank P = .26; adjusted hazard ratio [HR], 1.06; 95% CI, 0.83-1.36). Results were similar for people receiving vs not receiving dexamethasone at remdesivir initiation (dexamethasone recipients:
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