Introduction: Pneumococcal conjugate vaccine (PCV) impact studies have reported substantial reductions in the incidence of invasive pneumococcal disease (IPD) after implementation of childhood PCV programs. Heterogeneity in surveillance systems, local epidemiology and PCV programs hampers comparisons between studies. We aimed to better understand the impact of childhood PCV programs on overall IPD and serotype distribution. Areas covered: We analyzed the impact of PCV programs on the incidence of overall IPD, and the distribution of vaccine serotypes (VT) and non-vaccine serotypes (NVT) in children <5 years and adults ≥65 years old. We retrieved datasets from observational post-marketing studies and surveillance reports from countries with high-quality surveillance data available for at least 2 years before PCV program initiation and 3 years after higher-valent PCV implementation. We harmonized pre-and post-PCV analysis periods and assessment methods. Expert commentary: After introduction of pediatric PCV programs, the residual overall IPD burden in children was low and in a narrow range across countries with high vaccination coverage, irrespective of differences in PCV programs and pneumococcal epidemiology. Effects on overall IPD were more variable in the elderly. Whereas IPD was mainly due to VTs before PCV introduction, NVTs are the major contributor today in children and adults.ARTICLE HISTORY

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Effective global control of tuberculosis (TB) is increasingly threatened by the convergence of multidrug-resistant TB and the human immunodeficiency virus (HIV) infection. TB/HIV coinfections exert a tremendous burden on the host's immune system, and this has prompted the clinical use of immunomodulators to enhance host defences as an alternative therapeutic strategy. In this study, we modified the clinically used synthetic immunomodulatory pentapeptide, thymopentin (TP-5, RKDVY), with six arginine residues (RR-6, RRRRRR) at the N- and C-termini to obtain the cationic peptides, RR-11 (RKDVYRRRRRR-NH2) and RY-11 (RRRRRRRKDVY-NH2), respectively. The arginine residues conferred anti-mycobacterial activity to TP-5 in the peptides as shown by effective minimum inhibitory concentrations of 125 mg/L and killing efficiencies of >99.99% against both rifampicin-susceptible and -resistant Mycobacterium smegmatis. The immunomodulatory action of the peptides remained unaffected as shown by their ability to stimulate TNF-α production in RAW 264.7 mouse macrophage cells. A distinct change in surface morphology after peptide treatment was observed in scanning electron micrographs, while confocal microscopy and dye leakage studies suggested bacterial membrane disruption by the modified peptides. The modified peptides were non-toxic and did not cause hemolysis of rat red blood cells up to a concentration of 2000 mg/L. Moreover, RY-11 showed synergism with rifampicin and reduced the effective concentration of rifampicin, while preventing the induction of rifampicin resistance. The synthetic peptides may have a potential application in both immunocompetent and immunocompromised TB patients.

BackgroundDespite the significant amount of work being carried out to investigate the therapeutic potential of docosahexaenoic acid (DHA) in Alzheimer’s disease (AD), the mechanism by which DHA affects amyloid-β precursor protein (AβPP)-induced metabolic changes has not been studied.ObjectiveTo elucidate the metabolic phenotypes (metabotypes) associated with DHA therapy via metabonomic profiling of an AD cell model using gas chromatography time-of-flight mass spectrometry (GC/TOFMS).MethodsThe lysate and supernatant samples of CHO-wt and CHO-AβPP695 cells treated with DHA and vehicle control were collected and prepared for GC/TOFMS metabonomics profiling. The metabolic profiles were analyzed by multivariate data analysis techniques using SIMCA-P+ software.ResultsBoth principal component analysis and subsequent partial least squares discriminant analysis revealed distinct metabolites associated with the DHA-treated and control groups. A list of statistically significant marker metabolites that characterized the metabotypes associated with DHA treatment was further identified. Increased levels of succinic acid, citric acid, malic acid and glycine and decreased levels of zymosterol, cholestadiene and arachidonic acid correlated with DHA treatment effect. DHA levels were also found to be increased upon treatment.ConclusionOur study shows that DHA plays a role in mitigating AβPP-induced impairment in energy metabolism and inflammation by acting on tricarboxylic acid cycle, cholesterol biosynthesis pathway and fatty acid metabolism. The perturbations of these metabolic pathways by DHA in CHO-wt and CHO-AβPP695 cells shed further mechanistic insights on its neuroprotective actions.

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We demonstrate for the first time the dual effects of DHA in inhibiting HMG-CoA reductase and squalene epoxidase and modulating the sterol biosynthesis axis of the cholesterol pathway in AβPP overexpressing AD. Our novel findings underscore the potential of DHA as a multi-target hypocholesterolemic agent for the prophylaxis of AD and other cholesterol-associated diseases.

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