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Frontiers in Cellular and Infection... 2021(also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and... (Review)
Review
(also called pneumococcus) is not only a commensal that frequently colonizes the human upper respiratory tract but also a pathogen that causes pneumonia, sepsis, and meningitis. The mechanism of pneumococcal infection has been extensively studied, but the process of transmission has not been fully elucidated because of the lack of tractable animal models. Novel animal models of transmission have enabled further progress in investigating pneumococcal transmission mechanisms including the processes such as pneumococcal shedding, survival in the external environment, and adherence to the nasopharynx of a new host. Herein, we present a review on these animal models, recent research findings about pneumococcal transmission, and factors influencing the host-pneumococcus interaction.
Topics: Animals; Humans; Meningitis; Nasopharynx; Pneumococcal Infections; Pneumonia; Streptococcus pneumoniae
PubMed: 33996623
DOI: 10.3389/fcimb.2021.639450 -
Blood Advances Nov 2023Children with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for...
Children with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.
Topics: Humans; Child; Heptavalent Pneumococcal Conjugate Vaccine; Vaccines, Conjugate; Pneumococcal Infections; Serogroup; Anemia, Sickle Cell; Hemoglobin, Sickle
PubMed: 37698500
DOI: 10.1182/bloodadvances.2022009643 -
FEBS Letters Nov 2016Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a... (Review)
Review
Streptococcus pneumoniae (pneumococcus) has evolved sophisticated strategies to survive in several niches within the human body either as a harmless commensal or as a serious pathogen causing a variety of diseases. The dynamic interaction between pneumococci and resident host cells during colonization of the upper respiratory tract and at the site of infection is critical for bacterial survival and the development of disease. Pneumococcal lipoproteins are peripherally anchored membrane proteins and have pivotal roles in bacterial fitness including envelope stability, cell division, nutrient acquisition, signal transduction, transport (as substrate-binding proteins of ABC transporter systems), resistance to oxidative stress and antibiotics, and protein folding. In addition, lipoproteins are directly involved in virulence-associated processes such as adhesion, colonization, and persistence through immune evasion. Conversely, lipoproteins are also targets for the host response both as ligands for toll-like receptors and as targets for acquired antibodies. This review summarizes the multifaceted roles of selected pneumococcal lipoproteins and how this knowledge can be exploited to combat pneumococcal infections.
Topics: Bacterial Adhesion; Bacterial Proteins; Drug Resistance, Bacterial; Host-Pathogen Interactions; Humans; Immune Evasion; Lipoproteins; Pneumococcal Infections; Streptococcus pneumoniae; Virulence
PubMed: 27508940
DOI: 10.1002/1873-3468.12352 -
PloS One 2023Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to... (Review)
Review Meta-Analysis
INTRODUCTION
Experimental Human Pneumococcal Challenge (EHPC) involves the controlled exposure of adults to a specific antibiotic-sensitive Streptococcus pneumoniae serotype, to induce nasopharyngeal colonisation for the purpose of vaccine research. The aims are to review comprehensively the safety profile of EHPC, explore the association between pneumococcal colonisation and frequency of safety review and describe the medical intervention required to undertake such studies.
METHODS
A single-centre review of all EHPC studies performed 2011-2021. All recorded serious adverse events (SAE) in eligible studies are reported. An unblinded meta-analysis of collated anonymised individual patient data from eligible EHPC studies was undertaken to assess the association between experimental pneumococcal colonisation and the frequency of safety events following inoculation.
RESULTS
In 1416 individuals (median age 21, IQR 20-25), 1663 experimental pneumococcal inoculations were performed. No pneumococcal-related SAE have occurred. 214 safety review events were identified with 182 (12.85%) participants presenting with symptoms potentially in keeping with pneumococcal infection, predominantly in pneumococcal colonised individuals (colonised = 96/658, non-colonised = 86/1005, OR 1.81 (95% CI 1.28-2.56, P = <0.001). The majority were mild (pneumococcal group = 72.7% [120/165 reported symptoms], non-pneumococcal = 86.7% [124/143 reported symptoms]). 1.6% (23/1416) required antibiotics for safety.
DISCUSSION
No SAEs were identified directly relating to pneumococcal inoculation. Safety review for symptoms was infrequent but occurred more in experimentally colonised participants. Most symptoms were mild and resolved with conservative management. A small minority required antibiotics, notably those serotype 3 inoculated.
CONCLUSION
Outpatient human pneumococcal challenge can be conducted safely with appropriate levels of safety monitoring procedures in place.
Topics: Adult; Humans; Young Adult; Streptococcus pneumoniae; Pneumococcal Infections; Pneumococcal Vaccines; Nasopharynx; Anti-Bacterial Agents
PubMed: 37141259
DOI: 10.1371/journal.pone.0284399 -
Frontiers in Cellular and Infection... 2022
Topics: Humans; Nasopharynx; Pneumococcal Infections; Streptococcus pneumoniae
PubMed: 36176577
DOI: 10.3389/fcimb.2022.1028047 -
Clinical Microbiology and Infection :... Jan 2020Of over 90 serotypes of Streptococcus pneumoniae, only seven were included in the first pneumococcal conjugate vaccine (PCV). While PCV reduced the disease incidence, in... (Review)
Review
BACKGROUND
Of over 90 serotypes of Streptococcus pneumoniae, only seven were included in the first pneumococcal conjugate vaccine (PCV). While PCV reduced the disease incidence, in part because of a herd immunity effect, a replacement effect was observed whereby disease was increasingly caused by serotypes not included in the vaccine. Dynamic transmission models can account for these effects to describe post-vaccination scenarios, whereas economic evaluations can enable decision-makers to compare vaccines of increasing valency for implementation.
AIM
The aim of this review was to examine epidemiological and economic models and their assumptions for their potential contributions to future research and immunisation policy.
SOURCES
Pubmed, Scopus, Ovid, ISI Web of Knowledge, Centre of Reviews and Dissemination (CRD) databases were searched.
CONTENT
Twenty-three dynamic transmission models and 21 economic models were retrieved and reviewed. Published models employed various templates, revealing several key uncertainties regarding the biology and epidemiology of pneumococcal infection. While models suggested that PCVs will reduce the burden of disease, the extent to which they are predicted to do so depended on various assumptions regarding features of pneumococcal infection and epidemiology that governed PCV cost-effectiveness as well. Such features include the duration of protection and competitive interactions between serotypes, which are unclear at present, but which directly relate to herd immunity and serotype replacement.
IMPLICATIONS
Economic evaluations are not typically based on transmission dynamic models and hence omit indirect herd immunity effects. The two tools could be used in conjunction to inform decision-makers on vaccine implementation, but so far there have been few attempts to build economic evaluations on transmission dynamic models, and none in this field. Future directions for research could include studies to evaluate key parameters for the models involving herd immunity, serotype competition and the natural history of infection.
Topics: Cost-Benefit Analysis; Decision Support Techniques; Humans; Immunity, Herd; Models, Economic; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae; Vaccination; Vaccines, Conjugate
PubMed: 31055164
DOI: 10.1016/j.cmi.2019.04.026 -
ELife Jul 2022The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but... (Meta-Analysis)
Meta-Analysis
The characteristics of pneumococcal carriage vary between infants and adults. Host immune factors have been shown to contribute to these age-specific differences, but the role of pathogen sequence variation is currently less well-known. Identification of age-associated pathogen genetic factors could leadto improved vaccine formulations. We therefore performed genome sequencing in a large carriage cohort of children and adults and combined this with data from an existing age-stratified carriage study. We compiled a dictionary of pathogen genetic variation, including serotype, strain, sequence elements, single-nucleotide polymorphisms (SNPs), and clusters of orthologous genes (COGs) for each cohort - all of which were used in a genome-wide association with host age. Age-dependent colonization showed weak evidence of being heritable in the first cohort ( = 0.10, 95% CI 0.00-0.69) and stronger evidence in the second cohort ( = 0.56, 95% CI 0.23-0.87). We found that serotypes and genetic background (strain) explained a proportion of the heritability in the first cohort ( = 0.07, 95% CI 0.04-0.14 and = 0.06, 95% CI 0.03-0.13) and the second cohort ( = 0.11, 95% CI 0.05-0.21 and = 0.20, 95% CI 0.12-0.31). In a meta-analysis of these cohorts, we found one candidate association (p=1.2 × 10) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, while we did find a small effect of pathogen genome variation on pneumococcal carriage between child and adult hosts, this was variable between populations and does not appear to be caused by strong effects of individual genes. This supports proposals for adaptive future vaccination strategies that are primarily targeted at dominant circulating serotypes and tailored to the composition of the pathogen populations.
Topics: Adult; Carrier State; Child; Genome-Wide Association Study; Humans; Infant; Nasopharynx; Pneumococcal Infections; Pneumococcal Vaccines; Serogroup; Streptococcus pneumoniae
PubMed: 35881438
DOI: 10.7554/eLife.69244 -
Emerging Infectious Diseases Sep 2023Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated...
Streptococcus pneumoniae can co-infect persons who have viral respiratory tract infections. However, research on S. pneumoniae infections that are temporally associated with SARS-CoV-2 infections is limited. We described the epidemiology and clinical course of patients who had invasive pneumococcal disease (IPD) and temporally associated SARS-CoV-2 infections in Alaska, USA, during January 1, 2020-December 23, 2021. Of 271 patients who had laboratory-confirmed IPD, 55 (20%) had a positive SARS-CoV-2 test result. We observed no major differences in age, race, sex, or underlying medical conditions among IPD patients with and without SARS-CoV-2. However, a larger proportion of IPD patients with SARS-CoV-2 died (16%, n = 9) than for those with IPD alone (4%, n = 9) (p<0.01). IPD patients with SARS-CoV-2 were also more likely to be experiencing homelessness (adjusted OR 3.5; 95% CI 1.7-7.5). Our study highlights the risk for dual infection and ongoing benefits of pneumococcal and COVID-19 vaccination, especially among vulnerable populations.
Topics: Humans; Alaska; COVID-19 Vaccines; COVID-19; SARS-CoV-2; Pneumococcal Infections; Streptococcus pneumoniae; Pneumococcal Vaccines
PubMed: 37506683
DOI: 10.3201/eid2909.230080 -
Frontiers in Cellular and Infection... 2021Secondary bacterial infections enhance the disease burden of influenza infections substantially. (the pneumococcus) plays a major role in the synergism between... (Review)
Review
Secondary bacterial infections enhance the disease burden of influenza infections substantially. (the pneumococcus) plays a major role in the synergism between bacterial and viral pathogens, which is based on complex interactions between the pathogen and the host immune response. Here, we discuss mechanisms that drive the pathogenesis of a secondary pneumococcal infection after an influenza infection with a focus on how pneumococci senses and adapts to the influenza-modified environment. We briefly summarize what is known regarding secondary bacterial infection in relation to COVID-19 and highlight the need to improve our current strategies to prevent and treat viral bacterial coinfections.
Topics: COVID-19; Coinfection; Host-Pathogen Interactions; Humans; Influenza, Human; Pneumococcal Infections; Respiratory System; Respiratory Tract Infections; Streptococcus pneumoniae
PubMed: 33828999
DOI: 10.3389/fcimb.2021.643326 -
Human Vaccines & Immunotherapeutics Aug 2016Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine... (Review)
Review
Pneumococcal infection is a major cause of morbidity and mortality worldwide. The burden of disease associated with S. pneumoniae is largely preventable through routine vaccination. Pneumococcal conjugate vaccines (e.g. PCV7, PCV13) provide protection from invasive pneumococcal disease as well as non-invasive infection (pneumonia, acute otitis media), and decrease vaccine-type nasopharyngeal colonisation, thus reducing transmission to unvaccinated individuals. PCVs have also been shown to reduce the incidence of antibiotic-resistant pneumococcal disease. Surveillance for pneumococcal disease is important to understand local epidemiology, serotype distribution and antibiotic resistance rates. Surveillance systems also help to inform policy development, including vaccine recommendations, and monitor the impact of pneumococcal vaccination. National pneumococcal surveillance systems exist in a number of countries in Central and Eastern Europe (such as Croatia, Czech Republic, Hungary, Poland, Romania and Slovakia), and some have introduced PCVs (Czech Republic, Hungary, Kazakhstan, Russia, Slovakia and Turkey). Those countries without established programs (such as Kazakhstan, Russia and Ukraine) may be able to learn from the experiences of those with national surveillance systems. The serotype distributions and impact of PCV13 on pediatric pneumococcal diseases are relatively similar in different parts of the world, suggesting that approaches to vaccination used elsewhere are also likely to be effective in Central and Eastern Europe. This article briefly reviews the epidemiology of pneumococcal disease, presents the latest surveillance data from Central and Eastern Europe, and discusses any similarities and differences in these data as well the potential implications for vaccination policies in the region.
Topics: Epidemiological Monitoring; Europe; Health Policy; Humans; Immunization Programs; Pneumococcal Infections; Pneumococcal Vaccines
PubMed: 27096714
DOI: 10.1080/21645515.2016.1159363