The coexistence of multiple independently circulating strains in pathogen populations that undergo sexual recombination is a central question of epidemiology with profound implications for control. An agent-based model is developed that extends earlier ‘strain theory’ by addressing the var gene family of Plasmodium falciparum. The model explicitly considers the extensive diversity of multi-copy genes that undergo antigenic variation via sequential, mutually exclusive expression. It tracks the dynamics of all unique var repertoires in a population of hosts, and shows that even under high levels of sexual recombination, strain competition mediated through cross-immunity structures the parasite population into a subset of coexisting dominant repertoires of var genes whose degree of antigenic overlap depends on transmission intensity. Empirical comparison of patterns of genetic variation at antigenic and neutral sites supports this role for immune selection in structuring parasite diversity.DOI: http://dx.doi.org/10.7554/eLife.00093.001

No abstract

Background This study describes neuropsychological, medical, psychiatric and functional correlates of cognitive complaints experienced after recovery from acute COVID-19 infection. Methods Sixty participants underwent neuropsychological (NP), psychiatric, medical, functional, and quality of life assessments 6-8 months after acute COVID-19. Those seeking care cognitive complaints in a post-COVID-19 clinical program for Post-Acute Symptoms of COVID-19 (PASC) (Clinical Group, N=32) were compared to those recruited from the community who were not seeking care (Non-Clinical, N=28). A subset of participants underwent serological testing for pro-inflammatory cytokines C-Reactive Protein, Interleukin-6, and Tumor Necrosis Factor-α in order to explore correlations with neuropsychological, psychiatric and medical variables. Outcome For the entire sample, 16 (27%) had extremely low test scores (< 2 nd %ile on at least 1 NP test). The Clinical Group with cognitive complaints scored lower than age-adjusted population norms in tests of attention, processing speed, memory, and executive function, and significantly more scored in the extremely low range than the Non-Clinical Group (38% vs. 14%, p<0.04). The Clinical Group also reported higher levels of depression, anxiety, fatigue, PTSD and functional difficulties and lower quality of life. In logistic regression analysis, scoring in the extremely low range was predicted by acute COVID-19 symptoms, current depression score, number of medical comorbidities and subjective cognitive complaints in the areas of memory, language, and executive functions. IL-6 correlated with acute COVID symptoms, number of medical comorbidities, fatigue, and measures of executive function. CRP correlated with current COVID symptoms, depression score and, inversely, with quality of life. Conclusion Results suggest the existence of extremely low neuropsychological test performance experienced by some individuals months after acute COVID-19 infection, affecting multiple neurocognitive domains. This extremely low neuropsychological test performance is associated with worse acute COVID-19 symptoms, depression, medical comorbidities, functional complaints, and subjective cognitive complaints. Exploratory correlations with pro-inflammatory cytokines support further research into inflammatory mechanisms and viable treatments.

Background:Recent studies described an increase in acute kidney injury when high dose gentamicin was included in perioperative prophylaxis for orthopedic surgeries. To this effect, we compared the rate of nephrotoxicity for selected orthopedic surgeries where gentamicin was included (Gentamicin Group) to those where it was not included (Control Group) for perioperative prophylaxis and evaluated risk factors for nephrotoxicity.Methods:Spine, hip and knee surgeries performed between April 2011 and December 2013 were reviewed retrospectively. Gentamicin was given to eligible patients based on age, weight and Creatinine Clearance. Nephrotoxicity was assessed using Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) criteria.Results:Among selected surgeries (N = 1590 in Gentamicin Group: hip = 926, spine = 600, knee = 64; N = 2587 in Control Group: hip = 980, spine = 902, knee = 705), patients’ body weight, serum creatinine, comorbidities and surgery duration were similar in Gentamicin Group and Control Group. Gentamicin median dose was 4.5 mg/kg of dosing weight. Nephrotoxicity rate was 2.5% in Gentamicin Group and 1.8% in Control Group, p = 0.17. Most cases of nephrotoxicity were Risk category by RIFLE criteria (67% in Gentamicin Group and 72% in Control Group, p = 0.49). In logistic regression, risk factors for nephrotoxicity were hospital stay >1 day prior to surgery (odds ratio = 8.1; 95% confidence interval = 2.25–28.97, p = 0.001), knee or hip surgery (odds ratio = 4.7; 95% confidence interval = 2.9–9.48, p = 0.0005) and diabetes (odds ratio = 1.95; 95% confidence interval = 1.13–3.35, p = 0.016). Receipt of gentamicin was not an independent predictor of nephrotoxicity (odds ratio = 1.5; 95% confidence interval = 0.97–2.35, p = 0.07).Conclusion:In this cohort, rate of nephrotoxicity was similar between Gentamicin Group and Control Group. Single high dose gentamicin is a safe and acceptable option for perioperative prophylaxis in eligible patients undergoing orthopedic surgeries.

b Piperacillin-tazobactam (PTZ) is frequently used as empirical and targeted therapy for Gram-negative sepsis. Time-dependent killing properties of PTZ support the use of extended-infusion (EI) dosing; however, studies have shown inconsistent benefits of EI PTZ treatment on clinical outcomes. We performed a retrospective cohort study of adult patients who received EI PTZ treatment and historical controls who received standard-infusion (SI) PTZ treatment for presumed sepsis syndromes. Data on mortality rates, clinical outcomes, length of stay (LOS), and disease severity were obtained. A total of 843 patients (662 with EI treatment and 181 with SI treatment) were available for analysis. Baseline characteristics of the two groups were similar, except for fewer female patients receiving EI treatment. No significant differences between the EI and SI groups in inpatient mortality rates (10.9% versus 13.8%; P ‫؍‬ 0.282), overall LOS (10 versus 12 days; P ‫؍‬ 0.171), intensive care unit (ICU) LOS (7 versus 6 days; P ‫؍‬ 0.061), or clinical failure rates (18.4% versus 19.9%; P ‫؍‬ 0.756) were observed. However, the duration of PTZ therapy was shorter in the EI group (5 versus 6 days; P < 0.001). Among ICU patients, no significant differences in outcomes between the EI and SI groups were observed. Patients with urinary or intra-abdominal infections had lower mortality and clinical failure rates when receiving EI PTZ treatment. We did not observe significant differences in inpatient mortality rates, overall LOS, ICU LOS, or clinical failure rates between patients receiving EI PTZ treatment and patients receiving SI PTZ treatment. Patients receiving EI PTZ treatment had a shorter duration of PTZ therapy than did patients receiving SI treatment, and EI dosing may provide cost savings to hospitals.T he current prevalence of multidrug-resistant (MDR) Gramnegative infections challenges clinicians to ensure appropriate and pharmacokinetically optimized antimicrobial therapy for patients with presumed Gram-negative infections (1-5). Piperacillin-tazobactam (PTZ) is frequently administered as empirical or targeted therapy for hospitalized patients who have risk factors for Pseudomonas aeruginosa or other MDR Gram-negative organisms.␤-Lactam antimicrobials, including PTZ, exhibit time-dependent killing properties, in which fractional time above the MIC is a critical factor determining pharmacological outcomes (6, 7). Monte Carlo simulations have been used to identify a higher probability of target attainment when PTZ is administered using extended infusion (EI) or continuous infusion (CI) for Gram-negative infections, including P. aeruginosa (8-12).EI and CI PTZ protocols have been adopted in many hospitals in an effort to optimize the effectiveness of PTZ treatment. However, clinical studies have shown inconsistent benefits of EI versus standard-infusion (SI) PTZ protocols, in terms of mortality rates, length of stay (LOS), and clinical outcomes. Many of those studies were limited by small sample sizes, exclusion of patients who d...

We report here the incidental detection and complete genome sequence of a urinary Escherichia coli strain harboring mcr-1 and resistant to colistin in a New York patient returning from Portugal in 2016. This strain, with sequence type 1485 (ST1485), was a non-extended-spectrum beta-lactamase (ESBL) and non-carbapenemase producer and carried the mcr-1 gene on an IncHI2 plasmid.

In 2015, Clostridium difficile testing rates among 30 US community, multispecialty, and cancer hospitals were 14.0, 16.3, and 33.9/1,000 patient-days, respectively. Pooled hospital onset rates were 0.56, 0.84, and 1.57/1,000 patient-days, respectively. Higher testing rates may artificially inflate reported rates of C. difficile infection. C. difficile surveillance should consider testing frequency.

Complete genome sequences of nine enterovirus D68 (EV-D68) strains from patients in New York were obtained in 2016 by metagenomic next-generation sequencing. Comparative genomic analysis suggests that a new subclade B3, with ~4.5% nucleotide divergence from subclade B1 strains causing the 2014 outbreak, is circulating in the United States in 2016.