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Nature Reviews. Microbiology Jun 2018Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main... (Review)
Review
Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.
Topics: Bacterial Adhesion; Carrier State; Humans; Nasopharynx; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 29599457
DOI: 10.1038/s41579-018-0001-8 -
Glycoconjugate Journal Apr 2023Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use... (Review)
Review
Multivalent vaccines addressing an increasing number of Streptococcus pneumoniae types (7-, 10-, 13-, 15-, 20-valent) have been licensed over the last 22 years. The use of polysaccharide-protein conjugate vaccines has been pivotal in reducing the incidence of invasive pneumococcal disease despite the emergence of non-vaccine serotypes. Notwithstanding its undoubtable success, some weaknesses have called for continuous improvement of pneumococcal vaccination. For instance, despite their inclusion in pneumococcal conjugate vaccines, there are challenges associated with some serotypes. In particular, Streptococcus pneumoniae type 3 remains a major cause of invasive pneumococcal disease in several countries.Here a deep revision of the strengths and weaknesses of the licensed pneumococcal conjugate vaccines and other vaccine candidates currently in clinical development is reported.
Topics: Humans; Pneumococcal Vaccines; Streptococcus pneumoniae; Pneumococcal Infections; Vaccination; Vaccines, Conjugate; Antibodies, Bacterial
PubMed: 36652051
DOI: 10.1007/s10719-023-10100-3 -
F1000Research 2020The introduction of pneumococcal conjugate vaccines (PCVs) 7 and 13 into national childhood immunization programs in the US in 2000 and 2010, respectively, proved to be... (Review)
Review
The introduction of pneumococcal conjugate vaccines (PCVs) 7 and 13 into national childhood immunization programs in the US in 2000 and 2010, respectively, proved to be remarkably successful in reducing infant mortality due to invasive pneumococcal disease (IPD), resulting in widespread uptake of these vaccines. Secondary herd protection of non-vaccinated adults against IPD has proven to be an additional public health benefit of childhood immunization with PCVs, particularly in the case of the vulnerable elderly who are at increased risk due to immunosenescence and underlying comorbidity. Despite these advances in pneumococcal immunization, the global burden of pneumococcal disease, albeit of unequal geographic distribution, remains high. Reasons for this include restricted access of children living in many developing countries to PCVs, the emergence of infection due to non-vaccine serotypes of the pneumococcus, and non-encapsulated strains of the pathogen. Emerging concerns affecting the elderly include the realization that herd protection conferred by the current generation of PCVs (PCV7, PCV10, and PCV13) has reached a ceiling in many countries at a time of global population aging, compounded by uncertainty surrounding those immunization strategies that induce optimum immunogenicity and protection against IPD in the elderly. All of the aforementioned issues, together with a consideration of pipeline and pending strategies to improve access to, and serotype coverage of, PCVs, are the focus areas of this review.
Topics: Humans; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 32411353
DOI: 10.12688/f1000research.22341.1 -
International Journal of Molecular... Jul 2023Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of... (Review)
Review
The Global Burden of Community-Acquired Pneumonia in Adults, Encompassing Invasive Pneumococcal Disease and the Prevalence of Its Associated Cardiovascular Events, with a Focus on Pneumolysin and Macrolide Antibiotics in Pathogenesis and Therapy.
Despite innovative advances in anti-infective therapies and vaccine development technologies, community-acquired pneumonia (CAP) remains the most persistent cause of infection-related mortality globally. Confronting the ongoing threat posed by (the pneumococcus), the most common bacterial cause of CAP, particularly to the non-immune elderly, remains challenging due to the propensity of the elderly to develop invasive pneumococcal disease (IPD), together with the predilection of the pathogen for the heart. The resultant development of often fatal cardiovascular events (CVEs), particularly during the first seven days of acute infection, is now recognized as a relatively common complication of IPD. The current review represents an update on the prevalence and types of CVEs associated with acute bacterial CAP, particularly IPD. In addition, it is focused on recent insights into the involvement of the pneumococcal pore-forming toxin, pneumolysin (Ply), in subverting host immune defenses, particularly the protective functions of the alveolar macrophage during early-stage disease. This, in turn, enables extra-pulmonary dissemination of the pathogen, leading to cardiac invasion, cardiotoxicity and myocardial dysfunction. The review concludes with an overview of the current status of macrolide antibiotics in the treatment of bacterial CAP in general, as well as severe pneumococcal CAP, including a consideration of the mechanisms by which these agents inhibit the production of Ply by macrolide-resistant strains of the pathogen.
Topics: Adult; Humans; Aged; Pneumonia, Pneumococcal; Prevalence; Pneumococcal Infections; Streptococcus pneumoniae; Anti-Bacterial Agents; Macrolides; Community-Acquired Infections; Cardiovascular Diseases
PubMed: 37446214
DOI: 10.3390/ijms241311038 -
Der Internist Aug 2021Pneumococci are the most frequent bacterial agent of community-acquired pneumonia and are one of the most common vaccine-preventable causes of death worldwide. There is... (Review)
Review
Pneumococci are the most frequent bacterial agent of community-acquired pneumonia and are one of the most common vaccine-preventable causes of death worldwide. There is a polysaccharide vaccine that contains the capsular polysaccharides of 23 of the more than 90 known serotypes. PPV23 confers good protection against invasive pneumococcal infections but does not stimulate T cells and thus leaves no immunologic memory. It has limited efficacy in immunocompromised individuals. Initially for young children and later for adults, a 13 valent conjugate vaccine was licensed that covers fewer serotypes but leaves immunologic memory and mediates mucosal immunity, i.e. by eradicating healthy pneumococcal carriers, and thus has herd-protective effects. The German Standing Commission on Vaccination Practices (STIKO) currently recommends PPV23 for indication vaccination in various comorbidities and as standard vaccination for all above 60 years with repeat vaccination after 6 years at the earliest. Patients with immunosuppression, chronic renal failure or chronic liver failure should receive a sequential vaccination (first PCV13 followed by PPV23 after 6-12 months) due to the limited efficacy of PPV23 and their increased risk for infection.
Topics: Adult; Child; Child, Preschool; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 34251467
DOI: 10.1007/s00108-021-01100-2 -
Journal of Preventive Medicine and... Dec 2021To assess the prevalence of pneumococcal nasopharyngeal carriage, the role of potential risk factors, and the pneumococcal vaccination coverage among sheltered homeless...
OBJECTIVE
To assess the prevalence of pneumococcal nasopharyngeal carriage, the role of potential risk factors, and the pneumococcal vaccination coverage among sheltered homeless people in Marseille, France.
METHODS
During the winters 2015-2018, we enrolled 571 sheltered homeless males and 54 non-homeless controls. Streptococcus pneumoniae was directly searched from nasal/pharyngeal samples using real-time polymerase chain reaction.
RESULTS
The homeless people were mostly migrants from African countries, with a mean age of 43 years. Pneumococcal vaccination coverage was low (3.1%). The overall pneumococcal carriage rate was 13.0% and was significantly higher in homeless people (15.3% in 2018) than in controls (3.7%), with p = 0.033. Among homeless people, being aged ≥ 65 years (1.97, 95% CI; 1.01-3.87), living in a specific shelter (OR = 1.80, 95% CI: 1.06-3.05), and having respiratory signs and symptoms at the time of enrolment (OR = 2.55, 95% CI: 1.54-4.21) were independently associated with pneumococcal carriage.
CONCLUSION
Pneumococcal nasopharyngeal carriage, which is a precursor for pneumococcal disease in at-risk individuals, is frequent among French homeless people. Studies conducted in other countries have also reported outbreaks of pneumococcal infections in homeless people. Pneumococcal vaccination should be systematically considered for sheltered homeless people in France, as is being done in Canada since 2008.
Topics: Adult; Carrier State; Ill-Housed Persons; Humans; Infant; Male; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Prevalence; Streptococcus pneumoniae
PubMed: 35603253
DOI: 10.15167/2421-4248/jpmh2021.62.4.1805 -
Frontiers in Cellular and Infection... 2022The gram-positive bacterium is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts... (Review)
Review
The gram-positive bacterium is a leading cause of pneumonia, otitis media, septicemia, and meningitis in children and adults. Current prevention and treatment efforts are primarily pneumococcal conjugate vaccines that target the bacterial capsule polysaccharide, as well as antibiotics for pathogen clearance. While these methods have been enormously effective at disease prevention and treatment, there has been an emergence of non-vaccine serotypes, termed serotype replacement, and increasing antibiotic resistance among these serotypes. To combat , the immune system must deploy an arsenal of antimicrobial functions. However, has evolved a repertoire of evasion techniques and is able to modulate the host immune system. Antibodies are a key component of pneumococcal immunity, targeting both the capsule polysaccharide and protein antigens on the surface of the bacterium. These antibodies have been shown to play a variety of roles including increasing opsonophagocytic activity, enzymatic and toxin neutralization, reducing bacterial adherence, and altering bacterial gene expression. In this review, we describe targets of anti-pneumococcal antibodies and describe antibody functions and effectiveness against .
Topics: Adult; Antibodies, Bacterial; Child; Humans; Pneumococcal Infections; Pneumococcal Vaccines; Streptococcus pneumoniae; Vaccines, Conjugate
PubMed: 35155281
DOI: 10.3389/fcimb.2022.824788 -
Viruses Nov 2021Disease tolerance has emerged as an alternative way, in addition to host resistance, to survive viral-bacterial co-infections. Disease tolerance plays an important role... (Review)
Review
Disease tolerance has emerged as an alternative way, in addition to host resistance, to survive viral-bacterial co-infections. Disease tolerance plays an important role not in reducing pathogen burden, but in maintaining tissue integrity and controlling organ damage. A common co-infection is the synergy observed between influenza virus and that results in superinfection and lethality. Several host cytokines and cells have shown promise in promoting tissue protection and damage control while others induce severe immunopathology leading to high levels of morbidity and mortality. The focus of this review is to describe the host cytokines and innate immune cells that mediate disease tolerance and lead to a return to host homeostasis and ultimately, survival during viral-bacterial co-infection.
Topics: Coinfection; Cytokines; Homeostasis; Humans; Immunity, Innate; Influenza, Human; Orthomyxoviridae; Pneumococcal Infections; Streptococcus pneumoniae; Superinfection
PubMed: 34960631
DOI: 10.3390/v13122362 -
ELife May 2023is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in...
is a major pathogen in children, elderly subjects, and immunodeficient patients. Pentraxin 3 (PTX3) is a fluid-phase pattern recognition molecule (PRM) involved in resistance to selected microbial agents and in regulation of inflammation. The present study was designed to assess the role of PTX3 in invasive pneumococcal infection. In a murine model of invasive pneumococcal infection, PTX3 was strongly induced in non-hematopoietic (particularly, endothelial) cells. The IL-1β/MyD88 axis played a major role in regulation of the gene expression. mice presented more severe invasive pneumococcal infection. Although high concentrations of PTX3 had opsonic activity in vitro, no evidence of PTX3-enhanced phagocytosis was obtained in vivo. In contrast, -deficient mice showed enhanced recruitment of neutrophils and inflammation. Using deficient mice, we found that protection against pneumococcus was dependent upon PTX3-mediated regulation of neutrophil inflammation. In humans, gene polymorphisms were associated with invasive pneumococcal infections. Thus, this fluid-phase PRM plays an important role in tuning inflammation and resistance against invasive pneumococcal infection.
Topics: Animals; Mice; Inflammation; Neutrophils; Phagocytosis; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 37222419
DOI: 10.7554/eLife.78601 -
Frontiers in Immunology 2022Pneumolysin (PLY) is a pore-forming toxin produced by the human pathobiont , the major cause of pneumonia worldwide. PLY, a key pneumococcal virulence factor, can form... (Review)
Review
Pneumolysin (PLY) is a pore-forming toxin produced by the human pathobiont , the major cause of pneumonia worldwide. PLY, a key pneumococcal virulence factor, can form transmembrane pores in host cells, disrupting plasma membrane integrity and deregulating cellular homeostasis. At lytic concentrations, PLY causes cell death. At sub-lytic concentrations, PLY triggers host cell survival pathways that cooperate to reseal the damaged plasma membrane and restore cell homeostasis. While PLY is generally considered a pivotal factor promoting colonization and survival, it is also a powerful trigger of the innate and adaptive host immune response against bacterial infection. The dichotomy of PLY as both a key bacterial virulence factor and a trigger for host immune modulation allows the toxin to display both "Yin" and "Yang" properties during infection, promoting disease by membrane perforation and activating inflammatory pathways, while also mitigating damage by triggering host cell repair and initiating anti-inflammatory responses. Due to its cytolytic activity and diverse immunomodulatory properties, PLY is integral to every stage of pathogenesis and may tip the balance towards either the pathogen or the host depending on the context of infection.
Topics: Bacterial Proteins; Humans; Pneumococcal Infections; Streptococcus pneumoniae; Streptolysins; Virulence Factors
PubMed: 35529870
DOI: 10.3389/fimmu.2022.878244