Blood donor return behavior in South Africa and the United States before and during the COVID-19 pandemic.

Background: Studies preceding the COVID-19 pandemic found that slower time-to-return was associated with first-time, deferred, and mobile drive blood donors. How donor return dynamics changed during the COVID-19 pandemic is not well understood.

Methods: We analyzed visits by whole blood donors from 2017 to 2022 in South Africa (SA) and the United States (US) stratified by mobile and fixed environment, first-time and repeat donor status, and pre-COVID19 (before March 2020) and intra-COVID19.

Effect of antimicrobial peptides on planktonic growth, biofilm formation and biofilm-derived bacterial viability of .

is a leading cause of pneumonia mortality globally. Pneumococcal disease is often associated with prolonged colonisation of hosts and this process is facilitated by biofilm formation that is largely resistant to conventional antibiotics. We investigated the effects of antimicrobial peptides (AMPs) lysozyme, lactoferrin, LL37 and a combination of all three on planktonic growth, biofilm formation and biofilm-derived bacterial viability by , serotype 23F.

Cigarette smoke exposure induces expression of the pneumococcal erm(B) macrolide resistance gene.

Introduction: Cigarette smoking is a well-recognized risk factor for development of severe, invasive pneumococcal disease. However, little is known about the direct effects of exposure to cigarette smoke on the virulence mechanisms of the pathogen, particularly in respect of resistance to macrolide antibiotics, which are widely used in the treatment of pneumococcal infection. This study aimed to investigate the effects of exposure to cigarette smoke condensate (CSC, 80 and 160 mg/L) and clarithromycin (2 and 8 mg/L), alone and in combination , on expression of the (B) and (A) macrolide resistance genes of strains 2507 and 521 (both serotype 23F), respectively, of the pneumococcus.

Biofilm formation and induction of stress response genes is a common response of several serotypes of the pneumococcus to cigarette smoke condensate.

Objectives: Exposure to cigarette smoke impacts on the virulence of Streptococcus pneumoniae (pneumococcus) by mechanisms including induction of biofilm formation. Most studies, however, have focused on individual strains of the pneumococcus. Accordingly, the current study has investigated the commonality of the pneumococcal stress response to cigarette smoke condensate (CSC), using five different strains of the pathogen.

Interleukin-10 and interleukin-1 receptor antagonist distinguish between patients with sepsis and the systemic inflammatory response syndrome (SIRS).

The current study evaluated the potential of clinical parameters and circulating biomarkers to distinguish sepsis from SIRS in patients admitted with systemic inflammation. Clinical parameters, leukocyte counts and platelets were measured on admission. Circulating C-reactive protein (CRP), procalcitonin (PCT) and cytokine concentrations were quantified using laser immunonephelometry, immunoluminescence and a Bio-Plex suspension bead array system respectively.

Investigation of biofilm formation on a charged intravenous catheter relative to that on a similar but uncharged catheter.

Catheter-related blood stream infections increase morbidity, mortality, and costs. This study investigated whether Certofix(®) protect antimicrobial catheters carry a surface charge and whether this inhibits biofilm formation. The capacitance of the catheter surfaces was measured and, to determine if the catheters released ions, distilled water was passed through and current measured as a function of voltage.

Exposure of a 23F serotype strain of Streptococcus pneumoniae to cigarette smoke condensate is associated with selective upregulation of genes encoding the two-component regulatory system 11 (TCS11).

Alterations in whole genome expression profiles following exposure of the pneumococcus (strain 172, serotype 23F) to cigarette smoke condensate (160 μg/mL) for 15 and 60 min have been determined using the TIGR4 DNA microarray chip. Exposure to CSC resulted in the significant (P<0.014-0.

Overview of community-acquired pneumonia and the role of inflammatory mechanisms in the immunopathogenesis of severe pneumococcal disease.

Community-acquired pneumonia (CAP) remains a leading cause of morbidity and mortality among the infectious diseases. Despite the implementation of national pneumococcal polyvalent vaccine-based immunisation strategies targeted at high-risk groups, Streptococcus pneumoniae (the pneumococcus) remains the most common cause of CAP. Notwithstanding the HIV pandemic, major challenges confronting the control of CAP include the range of bacterial and viral pathogens causing this condition, the ever-increasing problem of antibiotic resistance worldwide, and increased vulnerability associated with steadily aging populations in developed countries.

Pathogen- and host-directed anti-inflammatory activities of macrolide antibiotics.

Macrolide antibiotics possess several, beneficial, secondary properties which complement their primary antimicrobial activity. In addition to high levels of tissue penetration, which may counteract seemingly macrolide-resistant bacterial pathogens, these agents also possess anti-inflammatory properties, unrelated to their primary antimicrobial activity. Macrolides target cells of both the innate and adaptive immune systems, as well as structural cells, and are beneficial in controlling harmful inflammatory responses during acute and chronic bacterial infection.

Effects of cigarette smoke condensate on pneumococcal biofilm formation and pneumolysin.

Although the well-recognised predisposition of cigarette smokers to the development of severe pneumococcal disease may be attributable to impairment of local host defences, less is known about the direct effects of smoke exposure on airway pathogens, or their virulence factors. In the current study, we have investigated the effects of cigarette smoke condensate (CSC) on biofilm formation by Streptococcus pneumoniae, and on the pore-forming activity of its major toxin, pneumolysin. Biofilm formation following exposure of the pneumococcus to CSC (20-160 μg·mL(-1)) was measured using a crystal violet-based spectrophotometric procedure, while the pore-forming activity of recombinant pneumolysin was determined by a fura-2/acetoxymethyl ester-based spectrofluorimetric procedure to monitor the uptake of extracellular Ca(2+) by isolated human neutrophils.

Calcium-dependent potentiation of the pro-inflammatory functions of human neutrophils by tigecycline in vitro.

Objectives: Tigecycline is the prototype of the recently introduced, intravenously administered glycylcycline class of antibiotics, developed in response to the increasing problem of antibiotic resistance in Gram-positive bacteria, especially Staphylococcus aureus, as well as Gram-negative bacteria and anaerobes. However, relatively little is known about the immunomodulatory potential of tigecycline, specifically its interactions with human neutrophils. In the current study we investigated the effects of tigecycline at therapeutically relevant concentrations and greater (0.

Beneficial and Harmful Interactions of Antibiotics with Microbial Pathogens and the Host Innate Immune System.

In general antibiotics interact cooperatively with host defences, weakening and decreasing the virulence of microbial pathogens, thereby increasing vulnerability to phagocytosis and eradication by the intrinsic antimicrobial systems of the host. Antibiotics, however, also interact with host defences by several other mechanisms, some harmful, others beneficial. Harmful activities include exacerbation of potentially damaging inflammatory responses, a property of cell-wall targeted agents, which promotes the release of pro-inflammatory microbial cytotoxins and cell-wall components.

Protein kinase C promotes restoration of calcium homeostasis to platelet activating factor-stimulated human neutrophils by inhibition of phospholipase C.

Background: The role of protein kinase C (PKC) in regulating the activity of phospholipase C (PLC) in neutrophils activated with the chemoattractant, platelet-activating factor (PAF, 20 and 200 nM), was probed in the current study using the selective PKC inhibitors, GF10903X (0.5 - 1 muM) and staurosporine (400 nM).

Methods: Alterations in cytosolic Ca2+, Ca2+ influx, inositol triphosphate (IP3), and leukotriene B4 production were measured using spectrofluorimetric, radiometric and competitive binding radioreceptor and immunoassay procedures, respectively.

An investigation of the role of oral epithelial cells and Langerhans cells as possible HIV viral reservoirs.

Background: The role of the oral mucosa as a target of human immunodeficiency virus (HIV-1) infection and persistence is unclear. HIV-1 has been reported in oral epithelial cells, but this has not been confirmed. Cellular reservoirs may impede antiretroviral therapies and should be identified.

Pneumolysin as a vaccine and drug target in the prevention and treatment of invasive pneumococcal disease.

Streptococcus pneumoniae (the pneumococcus) remains one of the major human pathogens and one of the most common causes of community-acquired pneumonia, otitis media, sinusitis, and meningitis. Aside from the threats posed by emerging antibiotic resistance and infection with the human immunodeficiency virus, the mortality rate among those patients with severe pneumococcal disease who receive seemingly appropriate antimicrobial chemotherapy remains unacceptably high. Because of its involvement in the pathogenesis of invasive disease, pneumolysin, one of the best-characterized virulence factors of the pneumococcus, represents not only a potential vaccine target, but also a target for adjunctive therapy to antibiotics in patients with acute pneumococcal disease.

Pneumolysin in the immunopathogenesis and treatment of pneumococcal disease.

Recent insights into the immunopathogenesis of pneumococcal infection, a common and significant cause of morbidity and mortality, have implicated pneumolysin as being a prominent virulence factor, which may play a role in microbial colonization, invasion and dissemination, as well as tissue inflammation. Being a highly immunogenic polypeptide produced by all clinically relevant pneumococcal isolates, pneumolysin is recognized as a potential carrier protein for polysaccharide conjugate vaccines, while in the setting of acute disease, promising pneumolysin-directed pharmacological strategies include, among others, macrolides and corticosteroids.

Pneumolysin potentiates oxidative inactivation of alpha-1-proteinase inhibitor by activated human neutrophils.

This study was designed to investigate the effects of the Streptococcus pneumoniae-derived, pro-inflammatory toxin, pneumolysin (8.37 and 41.75 ng/ml), on the oxidative inactivation of alpha-1-protease inhibitor (API) by chemoattractant-activated human neutrophils in vitro.

Docosahexaenoic acid and eicosapentaenoic acid antagonize the proinflammatory interactions of pneumolysin with human neutrophils.

Pneumolysin (4.18 ng/ml)-mediated influx of Ca(2+) and augmentation of the chemoattractant-activated generation of reactive oxidants was antagonized by pretreatment of human neutrophils with the omega-3 polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid (1.25 to 5 microg/ml).

Pneumolysin activates the synthesis and release of interleukin-8 by human neutrophils in vitro.

The effects that the Streptococcus pneumoniae-derived, proinflammatory toxin, pneumolysin (8.37 and 41.75 ng/mL), has on the production of interleukin (IL)-8 and tumor-necrosis factor (TNF)-alpha by human neutrophils have been investigated in vitro.

The role of pneumolysin in the pathogenesis of Streptococcus pneumoniae infection.

In addition to being cytotoxic for eukaryotic cells, recent research has clearly indicated that pneumolysin at sub-cytolytic concentrations potentiates the proinflammatory activities of neutrophils and macrophages. Together these cytotoxic and proinflammatory activities of the toxin are likely to contribute to the virulence of the pneumococcus, particularly in facilitating adherence, invasion and dissemination of this important microbial pathogen. Pneumolysin-based vaccine strategies, although in the early stages of development and evaluation, show promise in reducing the severity of pneumococcal disease.