Background Hybrid immunity is associated with more durable protection against COVID-19. We describe the antibody responses following SARS-CoV-2 infection in vaccinated and unvaccinated individuals. Methods The 55 vaccine-arm COVID-19 cases diagnosed during the blinded phase of the Coronavirus Efficacy trial were matched with 55 placebo-arm COVID-19 cases. Pseudovirus neutralizing antibody (nAb) activity to the ancestral strain and binding antibody (bAb) responses to nucleocapsid and spike antigens [ancestral and variants of concern (VOC)] were assessed on Disease Day 1 (DD1) and 28 days later (DD29). Results The primary analysis set was 46 vaccine cases and 49 placebo cases with COVID-19 at least 57 days post-first dose. For vaccine-group cases, there was a 1.88-fold rise in ancestral anti-spike bAbs one month post-disease onset, although 47% had no increase. The vaccine-to-placebo geometric mean ratios for DD29 anti-spike and anti-nucleocapsid bAbs were 6.9 and 0.04, respectively. DD29 mean bAb levels were higher for vaccine vs. placebo cases for all VOCs. DD1 nasal viral load positively correlated with bAb levels in the vaccine group. Conclusions Following COVID-19, vaccinated participants had higher levels and breadth of anti-spike bAbs and higher nAb titers than unvaccinated participants. These were largely attributable to the primary immunization series.
Pseudomonas aeruginosa secretes numerous toxins and destructive enzymes that play distinct roles in pathogenesis. The Type III secretion system (T3SS) of Pseudomonas is a system that delivers a subset of toxins directly into the cytoplasm of eukaryotic cells. The secreted effectors include ExoS, ExoT, ExoU, and ExoY. In this chapter, we describe methods to induce T3S expression and measure the enzymatic activities of each effector in in vitro assays. ExoU is a phospholipase and its activity can be measured in a fluorescence-based assay monitoring the cleavage of the fluorogenic substrate, PED6. ExoS and ExoT both possess ADP-ribosyltransferase (ADPRT) and GTPase-activating protein (GAP) activity. ADPRT activity can be assessed by using radiolabeled nicotinamide adenine dinucleotide (NAD+) and measuring the covalent incorporation of ADP-ribose into a target protein. GAP activity is measured by the release of radiolabeled phosphate from [γ-32P]GTP-bound target proteins. In accordance with recent trends towards reducing the use of radioactivity in the laboratory, alternative assays using fluorescent or biotin-labeled reagents are described. ExoY is a nucleotidyl cyclase; cAMP production stimulated by ExoY can be monitored using reverse-phase HPLC or with commercially available immunological assays.
Background The disease burden of influenza‐associated hospitalizations among children in Jordan is not well established. We aimed to characterize hospitalizations attributed to influenza in a pediatric population. Methods We conducted a cross‐sectional study from our viral surveillance cohort in children under 2 years hospitalized with acute respiratory symptoms and/or fever from March 2010 to March 2013. We collected demographic and clinical characteristics, and calculated the frequency of children who met the severe acute respiratory illness (SARI) criteria. Nasal specimens were tested using real‐time reverse transcriptase polymerase chain reaction to detect influenza A, B, or C. Further subtyping for influenza A‐positive isolates was conducted. Results Of the 3168 children enrolled in our study, 119 (4%) were influenza‐positive. Influenza types and subtypes varied by season but were predominantly detected between December and February. Codetection of multiple respiratory pathogens was identified in 58% of children with the majority occurring among those <6 months. Bronchopneumonia and rule‐out sepsis were the most common admission diagnoses, with influenza A accounting for over 2/3 of children with a rule‐out sepsis admission status. One‐third of children under 6 months compared to 3/4 of children 6‐23 months met the SARI criteria. Conclusions Influenza was an important cause of acute respiratory illness in children under 2 years. Children <6 months had the highest burden of influenza‐associated hospitalizations and were less likely to meet the SARI global surveillance case definition. Additional surveillance is needed in the Middle East to determine the true influenza burden on a global scale.
Objectives We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis. Patients and methods A prospective and opportunistic pharmacokinetic (PK) study was conducted in 130 critically ill patients in two ICU sites. The plasma concentrations of cefepime were determined using a validated LC-MS/MS method. All cefepime PK data were analysed simultaneously using the non-linear mixed-effects modelling approach. Monte Carlo simulations were performed to evaluate the PTA of cefepime at different MIC values following different dose regimens in subjects with different renal functions. Results The PK of cefepime in critically ill patients was best characterized by a two-compartment model with zero-order input and first-order elimination. Creatinine clearance and body weight were identified to be significant covariates. Our simulation results showed that prolonged 3 h infusion does not provide significant improvement on target attainment compared with the traditional intermittent 0.5 h infusion. In contrast, for a given daily dose continuous infusion provided much higher breakpoint coverage than either 0.5 h or 3 h intermittent infusions. To balance the target attainment and potential neurotoxicity, cefepime 3 g/day continuous infusion appears to be a better dosing regimen than 6 g/day continuous infusion. Conclusions Continuous infusion may represent a promising strategy for cefepime treatment in critically ill patients. With the availability of institution- and/or unit-specific cefepime susceptibility patterns as well as individual patients’ renal function, our PTA results may represent useful references for physicians to make dosing decisions.
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