1,721,158 research outputs found
The nasopharyngeal microbiome
No full textHuman microbiomes have received increasing attention over the last 10 years, leading to a pervasiveness of hypotheses relating dysbiosis to health and disease. The respiratory tract has received much less attention in this respect than that of, for example, the human gut. Nevertheless, progress has been made in elucidating the immunological, ecological and environmental drivers that govern these microbial consortia and the potential consequences of aberrant microbiomes. In this review, we consider the microbiome of the nasopharynx, a specific niche of the upper respiratory tract. The nasopharynx is an important site, anatomically with respect to its gateway position between upper and lower airways, and for pathogenic bacterial colonisation. The dynamics of the latter are important for long-term respiratory morbidity, acute infections of both invasive and non-invasive disease and associations with chronic airway disease exacerbations. Here, we review the development of the nasopharyngeal (NP) microbiome over the life course, examining it from the early establishment of resilient profiles in neonates through to perturbations associated with pneumonia risk in the elderly. We focus specifically on the commensal, opportunistically pathogenic members of the NP microbiome that includes Streptococcus pneumoniae, Staphylococcus aureus, Haemophilus influenzae and Moraxella catarrhalis. In addition, we consider the role of relatively harmless genera such as Dolosigranulum and Corynebacterium. Understanding that the NP microbiome plays such a key, beneficial role in maintaining equilibrium of commensal species, prevention of pathogen outgrowth and host immunity enables future research to be directed appropriately
Secondary bacterial infections associated with influenza pandemics
No full textLower and upper respiratory infections are the fourth highest cause of global mortality (Lozano et al., 2012). Epidemic and pandemic outbreaks of respiratory infection are a major medical concern, often causing considerable disease and a high death toll, typically over a relatively short period of time. Influenza is a major cause of epidemic and pandemic infection. Bacterial co/secondary infection further increases morbidity and mortality of influenza infection, with Streptococcus pneumoniae, Haemophilus influenzae and Staphylococcus aureus reported as the most common causes. With increased antibiotic resistance and vaccine evasion it is important to monitor the epidemiology of pathogens in circulation to inform clinical treatment and development, particularly in the setting of an influenza epidemic/pandemic
Analysis and interpretation of the human microbiome
Full text linkMicrobiome research has experienced an unprecedented level of growth over the last decade. This is largely due to revolutionary developments in, and accessibility to, DNA sequencing technologies that have enabled laboratories with even modest budgets to undertake projects. Study of the human microbiome in particular has seen a surge in interest, and although a lot of time and money has been focused on health and disease, the clinical interpretation of these data and the ability of clinicians to understand these studies in the context of disease are less straightforward. Conditions such as inflammatory bowel disease, asthma, and cancer have seen a huge increase in research focused on the role of microbiome in disease pathogenesis, but the ability of clinicians to appraise and use these data is largely lacking. The purpose of this article is to provide an introduction for clinicians and nonclinicians wishing to learn about and engage in microbiome research. It details the background of microbiome research and discusses the process of generating 16S rRNA sequencing data, the most commonly used method for microbiome analysis. We discuss the interpretation of results in a clinical context, commonly used metrics for analysis and discuss future impact and direction for microbiome research. The meteoric rise of genomic medicine to the brink of routine clinical use should be seen as a blueprint for the microbiome; the ability for physicians to understand and interpret these data is vital to this growth and aiding clinicians (and researchers) to participate in further microbiome research
Serotype distribution of disease-causing Streptococcus pneumoniae in Thailand: A systematic review
No full textBackground
Streptococcus pneumoniae infection is associated with a high morbidity and mortality worldwide. There are currently >98 known serotypes; the most burdensome are covered by current pneumococcal conjugate vaccines (PCVs) such as PCV10 (Synflorix®) and (Prevnar 13®) PCV13. However, at present no PCV is available on the National Expanded Programme of Immunization (EPI) in Thailand.
Methods
Here we report a systematic review of studies regarding pneumococci associated with invasive pneumococcal disease (IPD) and non-IPD in Thailand. The NCBI PubMed database and Google Scholar were used to identify relevant papers published from 1st January 1990 to 21st August 2017. The quantitative analysis was reported as the distribution of serotypes across two age groups, ≤5 and >5 years old, as these were the most commonly reported. Where age was not stated, or data was combined, data were categorised as all ages.
Results
The search returned 15 relevant articles. From these the five most common disease-causing serotypes, in rank order, were 6B, 23F, 14, 19A and 19F. Vaccine coverage would be 55.3% for PCV10 and 69.7% for PCV13. There was insufficient data to draw conclusions regarding non-invasive disease-causing pneumococcal serotypes.
Conclusion
This review demonstrates that the serotypes which were most responsible for disease in Thailand are included in PCV10 and PCV13. Better surveillance data of IPD and non-IPD are required for monitoring vaccine effectiveness if PCV is implemented nationally
NTHi-IAV coinfection of macrophages alters infection outcomes and inflammatory responses
No full textNontypeable Haemophilus influenzae (NTHi) chronically colonises the airway of individuals with chronic respiratory disease, with persistence suggested to be facilitated by invasion of airway macrophages. Previous data supports an interaction between NTHi colonisation and the risk of viruses exacerbating underlying respiratory diseases. As exacerbations are the main cause of morbidity and mortality of respiratory diseases, the drivers of this increased risk need to be identified.The aim of this work was to investigate whether prior NTHi infection compromises the ability of macrophages to respond to a subsequent viral challenge. A monocyte-derived macrophage (MDM)-NTHi intracellular persistence model was adapted to include coinfection with the influenza A virus (IAV). Compared to pathogen-alone controls, NTHi presence significantly increased by 190% (p<0.05), whereas the percentage of IAV-infected MDM significantly decreased (23.9% to 6.8%, p<0.01) during co-infection. This decreased viral infection was associated with NTHi-mediated transcriptomic upregulation of MDM antiviral responses (FDR p<0.05) and IFN-β release (p<0.05) prior to IAV challenge. Coinfected MDM released higher levels of inflammatory mediators (TNF-α, IL-1β, IL-6, IL-8, IL-15, IL-23 and IL-36β, all p<0.05) compared to IAV infection alone.This work demonstrates that although prior NTHi infection primed MDM to better respond to IAV infection, coinfection resulted in increased NTHi load and MDM pro-inflammatory responses. Considering the interactions of colonising airway bacteria and viral infections on host immune responses may better inform on treatment strategies to reduce exacerbations.<br/
The characterization of Moraxella catarrhalis carried in the general population
Full text linkMoraxella catarrhalis is a common cause of respiratory tract infection, particularly otitis media in children, whilst it is also associated with the onset of exacerbation in chronic obstructive pulmonary disease in adults. Despite the need for an efficacious vaccine against M. catarrhalis, no candidates have progressed to clinical trial. This study, therefore, aimed to characterize the diversity of M. catarrhalis isolated from the upper respiratory tract of healthy children and adults, to gain a better understanding of the epidemiology of M. catarrhalis and the distribution of genes associated with virulence factors, to aid vaccine efforts. Isolates were sequenced and the presence of target genes reported. Contrary to prevailing data, this study found that lipooligosaccharide (LOS) B serotypes are not exclusively associated with 16S type 1. In addition, a particularly low prevalence of LOS B and high prevalence of LOS C serotypes was observed. M. catarrhalis isolates showed low prevalence of antimicrobial resistance and a high gene prevalence for a number of the target genes investigated: ompB2 (also known as copB), ompCD, ompE, ompG1a, ompG1b, mid (also known as hag), mcaP, m35, tbpA, lbpA, tbpB, lbpB, msp22, msp75 and msp78, afeA, pilA, pilQ, pilT, mod, oppA, sbp2, mcmA and mclS.</p
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Strain-dependent effects of Nontypeable Haemophilus influenzae (NTHi) on human macrophage function
No full textNontypeable Haemophilus influenzae (NTHi) is a heterogeneous respiratory tract pathogen implicated in opportunistic infections and exacerbations of chronic respiratory diseases, such as COPD and asthma. In these diseases, airway macrophages have impaired phagocytic ability, contributing to chronic airway colonisation by NTHi. It is unclear whether macrophage responses to NTHi are strain-dependent, highlighting a possible mechanism by which certain NTHi strains can persist within the airway. The aim of this work was to characterise macrophage responses following infection with different clinical strains of NTHi.Monocyte-derived macrophages (MDM) isolated from blood of healthy volunteers were infected with NTHi ST14 or ST201 for 6h, incubated with antibiotics for a further 18h, followed by inflammatory pathway analysis by PCR or ELISA. Measurement of NTHi hel gene expression demonstrated increased presence of ST14, compared to ST201 in MDM at 24h (p<0.05). MDM expression of IFNß, TLR4 and TLR7 was not significantly different between strains. However, MDM expression of CXCL10, RIG-I and NFκB was induced significantly more by ST14 (p<0.05). In contrast, levels of CXCL10 released into MDM supernatants did not differ between the two strains. However, MDM production of IL1ß, IL6 and IL8 was higher in response to ST14 infection compared to ST201 (p<0.05).This work suggests that ST14 is more persistent in MDM than ST201, resulting in increased expression of inflammatory markers. These data indicate that MDM respond differently to different NTHi strains. Investigating these strain differences will increase our understanding of the role of NTHi in exacerbations of chronic respiratory diseas
The response of macrophages to Moraxella catarrhalis infection
No full textInfection by certain bacterial species can predispose an individual to developing asthma and trigger asthmatic exacerbations. Moraxella catarrhalis is one such organism, yet there is little data on the innate immune responses to this pathogen. Alveolar macrophages are the predominant immune cell isolated from the airway and show phenotypic differences in health and asthma. Macrophages are crucial in the immune response by pathogen recognition receptor (PRR)mediated detection of organisms, release of pro-inflammatory mediators and presentation of antigens to other cells of the immune system to link the innate and adaptive immune response. The aim of this work was to investigate the response of macrophages to M.catarrhalis. Monocyte-derived macrophages (MDM) were exposed to M.catarrhalis for 2h, incubated with antiobiotics for 22h before analysis at 24h. The expression of PRRs were analysed by real time PCR. A significant increase of retinoic acid-inducible gene(RIG)I expression(p<0.0001) was found; however, IFN-β was not detected. Conversely, expression of toll-like receptor (TLR)4 decreased(p=0.0003). Despite this, the release of IL-1β and IL-8 was detected in a dose-dependent manner by ELISA(p<0.0001). The surface expression of antigen presentation molecules were analysed by flow cytometry and showed an upregulation of major histocompatibility complex (MHC)-II(p=0.002) and MR1(p=0.0015), but only a slight upregulation of MHC-I(p=0.0728). This work suggests that MDM respond to M.catarrhalis and act to induce further immune cell effector actions. Understanding the MDM response to M.catarrhalis will allow for future comparisons to determine differences between the phenotypically distinctive macrophages in health and asthma
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