scholarly journals Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniae serotype 1 genotypes in healthy Gambians before and after the 7-valent pneumococcal conjugate vaccine

2014 ◽  
Author(s):  
Chinelo Ebruke ◽  
Anna Roca ◽  
Uzochukwu Egere ◽  
Ousainou Darboe ◽  
Philip C Hill ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epidemiological Studies ◽  
Temporal Changes ◽  
Nasopharyngeal Carriage ◽  
Post Vaccination ◽  
Period 2 ◽  
Serotype 1 ◽  
Pneumococcal Serotype ◽  
The Impact ◽  
Vaccination Period

Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease. However this invasive serotype is hardly found in nasopharyngeal asymptomatic carriage and therefore large epidemiological studies are needed to assess the dynamics of serotype 1 infection. Within the context of a large cluster randomized trial conducted in rural Gambia to assess the impact of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary study describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1 and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS) were collected before PCV-7 vaccination (December 2003-May 2004) and up to 30 months after PCV-7 vaccination (post-vaccination periods 1 to 3: July 2006 – March 2007; April 2007 – March 2008 and April 2008 – Feb 2009). S. pneumoniae serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of 12,319 NPS samples collected. In the pre-vaccination period, prevalence of serotype 1 was 0.47% in both study arms. In the post-vaccination periods, prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and 0.165% in period 2; while prevalence in partly vaccinated villages was between 0.17% in period 3 and 1.34% in period 2. Overall four different genotypes were obtained with ST3081 the most prevalent (60.71%) followed by ST618 929.76%). ST3081 was found only in post-vaccination period 2 and 3 while ST618 had disappeared in post-vaccination period 3. Distribution of these major genotypes was similar in both study arms.Emergence of ST3081 and concomitant disappearance of ST618 may suggest a change in the molecular epidemiology of pneumococcal serotype 1 in this region. This change is not likely to be associated with the introduction of PCV-7 which lacks serotype 1 as it was observed simultaneously in both study arms. Future population-based epidemiological studies will provide further evidence of substantive changes in the pneumococcal serotype 1 epidemiology and the likely mechanisms.

scholarly journals Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniae serotype 1 genotypes in healthy Gambians before and after the 7-valent pneumococcal conjugate vaccine

2014 ◽  
Author(s):  
Chinelo Ebruke ◽  
Anna Roca ◽  
Uzochukwu Egere ◽  
Ousainou Darboe ◽  
Philip C Hill ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Epidemiological Studies ◽  
Temporal Changes ◽  
Nasopharyngeal Carriage ◽  
Post Vaccination ◽  
Period 2 ◽  
Serotype 1 ◽  
Pneumococcal Serotype ◽  
The Impact ◽  
Vaccination Period

Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease. However this invasive serotype is hardly found in nasopharyngeal asymptomatic carriage and therefore large epidemiological studies are needed to assess the dynamics of serotype 1 infection. Within the context of a large cluster randomized trial conducted in rural Gambia to assess the impact of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary study describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1 and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS) were collected before PCV-7 vaccination (December 2003-May 2004) and up to 30 months after PCV-7 vaccination (post-vaccination periods 1 to 3: July 2006 – March 2007; April 2007 – March 2008 and April 2008 – Feb 2009). S. pneumoniae serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of 12,319 NPS samples collected. In the pre-vaccination period, prevalence of serotype 1 was 0.47% in both study arms. In the post-vaccination periods, prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and 0.165% in period 2; while prevalence in partly vaccinated villages was between 0.17% in period 3 and 1.34% in period 2. Overall four different genotypes were obtained with ST3081 the most prevalent (60.71%) followed by ST618 929.76%). ST3081 was found only in post-vaccination period 2 and 3 while ST618 had disappeared in post-vaccination period 3. Distribution of these major genotypes was similar in both study arms.Emergence of ST3081 and concomitant disappearance of ST618 may suggest a change in the molecular epidemiology of pneumococcal serotype 1 in this region. This change is not likely to be associated with the introduction of PCV-7 which lacks serotype 1 as it was observed simultaneously in both study arms. Future population-based epidemiological studies will provide further evidence of substantive changes in the pneumococcal serotype 1 epidemiology and the likely mechanisms.

scholarly journals Genomic Characteristics of Invasive Streptococcus pneumoniae Serotype 1 in New Caledonia Prior to the Introduction of PCV13

2020 ◽  
Vol 14 ◽  
pp. 117793222096210 ◽  
Author(s):  
Mariem Hanachi ◽  
Anmol Kiran ◽  
Jennifer Cornick ◽  
Emna Harigua-Souiai ◽  
Dean Everett ◽  
...  
Keyword(s):  
Population Structure ◽  
Streptococcus Pneumoniae ◽  
Virulence Genes ◽  
New Caledonia ◽  
Disease Outbreaks ◽  
Genomic Diversity ◽  
Whole Genome Sequence ◽  
Serotype 1 ◽  
The Impact ◽  
Sequence Types

Streptococcus pneumoniae serotype 1 is a common cause of global invasive pneumococcal disease. In New Caledonia, serotype 1 is the most prevalent serotype and led to two major outbreaks reported in the 2000s. The pneumococcal conjugate vaccine 13 (PCV13) was introduced into the vaccination routine, intending to prevent the expansion of serotype 1 in New Caledonia. Aiming to provide a baseline for monitoring the post-PCV13 changes, we performed a whole-genome sequence analysis on 67 serotype 1 isolates collected prior to the PCV13 introduction. To highlight the S. pneumoniae serotype 1 population structure, we performed a multilocus sequence typing (MLST) analysis revealing that NC serotype 1 consisted of 2 sequence types: ST3717 and the highly dominant ST306. Both sequence types harbored the same resistance genes to beta-lactams, macrolide, streptogramin B, fluoroquinolone, and lincosamide antibiotics. We have also identified 36 virulence genes that were ubiquitous to all the isolates. Among these virulence genes, the pneumolysin sequence presented an allelic profile associated with disease outbreaks and reduced hemolytic activity. Moreover, recombination hotspots were identified in 4 virulence genes and more notably in the cps locus ( cps2L), potentially leading to capsular switching, a major mechanism of the emergence of nonvaccine types. In summary, this study represents the first overview of the genomic characteristics of S. pneumoniae serotype 1 in New Caledonia prior to the introduction of PCV13. This preliminary description represents a baseline to assess the impact of PCV13 on serotype 1 population structure and genomic diversity.

scholarly journals Structural insights into loss of function of a pore forming toxin and its role in pneumococcal adaptation to an intracellular lifestyle

2020 ◽  
Author(s):  
Dilip C. Badgujar ◽  
Anjali Anil ◽  
Angharad E. Green ◽  
Manalee Vishnu Surve ◽  
Shilpa Madhavan ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Tissue Damage ◽  
Inflammatory Responses ◽  
Hydrophobic Interactions ◽  
Structural Basis ◽  
Nasopharyngeal Carriage ◽  
Loss Of Function ◽  
Serotype 1 ◽  
Domain 3

ABSTRACTThe opportunistic pathogen Streptococcus pneumoniae has dual lifestyles: one of an asymptomatic colonizer in the human nasopharynx and the other of a deadly pathogen invading sterile host compartments. The latter triggers an overwhelming inflammatory response, partly driven via pore forming activity of the cholesterol dependent cytolysin (CDC), pneumolysin. Although pneumolysin-induced inflammation drives person-to-person transmission from nasopharynx, the primary reservoir for pneumococcus, it also contributes to high mortality rates, creating a bottleneck that hampers widespread bacterial dissemination, thus acting as a double-edged sword. Serotype 1 ST306, a widespread pneumococcal clone, harbours a non-hemolytic variant of pneumolysin (Ply-NH). Performing crystal structure analysis of Ply-NH, we identified Y150H and T172I as key substitutions responsible for loss of its pore forming activity. We uncovered a novel inter-molecular cation-π interaction, governing formation of the transmembrane β-hairpins (TMH) in the pore state of Ply, which can be extended to other CDCs. H150 in Ply-NH disrupts this interaction, while I172 provides structural rigidity to domain-3, through hydrophobic interactions, inhibiting TMH formation. Loss of pore forming activity enabled improved cellular invasion and autophagy evasion, promoting an atypical intracellular lifestyle for pneumococcus, a finding that was corroborated in in vivo infection models. Attenuation of inflammatory responses and tissue damage promoted tolerance of Ply-NH-expressing pneumococcus in the lower respiratory tract. Adoption of this altered lifestyle may be necessary for ST306 due to its limited nasopharyngeal carriage, with loss of pore forming ability of Ply facilitating a benign association of SPN in an alternative, intracellular host niche.AUTHOR SUMMARYStreptococcus pneumoniae, the main causative agent of pneumonia, triggers inflammation and tissue damage by expressing a pore-forming toxin, pneumolysin (Ply). Ply-induced inflammation drives pneumococcal transmission from nasopharynx (its primary reservoir), but also contributes to host mortality, limiting its occupiable habitats. Here, we uncovered the structural basis for loss of pore-forming activity of a Ply variant, present in Serotype 1 ST306, and observed that this enabled adoption of an intracellular lifestyle, attenuating inflammatory responses and prolonging host tolerance of pneumococcus in the lower airways. This commensal-like lifestyle, resembling that of members of the mitis group of Streptococci, might have evolved within ST306 by loss of function ply mutations, compensating for limited nasopharyngeal carriage capacity by facilitating adaptation to an alternate niche.

A Tale of 2 Pneumos: The Impact of Human Immunodeficiency Virus Exposure or Infection Status on Pediatric Nasopharyngeal Carriage of Streptococcus pneumoniae and Pneumocystis jiroveci: A Nested Case Control Analysis From the Pneumonia Etiology Research In Child Health Study

2020 ◽  
Author(s):  
Ingrid Y Camelo ◽  
Lawrence M Mwananyanda ◽  
Donald M Thea ◽  
Philip Seidenberg ◽  
Christopher J Gill ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Streptococcus Pneumoniae ◽  
Morbidity And Mortality ◽  
Pneumocystis Jirovecii ◽  
Control Analysis ◽  
Nasopharyngeal Carriage ◽  
Immunodeficiency Virus ◽  
Living With Hiv ◽  
The Impact ◽  
Carriage Prevalence

Abstract Background The majority of pediatric human immunodeficiency virus (HIV) cases in Africa reflect maternal-to-child transmission. HIV exposed but uninfected (HEU) children have increased rates of morbidity and mortality when compared to HIV unexposed and uninfected (HUU) children. The mechanisms behind these unexpected trends are only partially understood but could be explained by the differences in the immune response to infections triggered by an altered immune system state. Methods Using quantitative reverse transcription polymerase chain reaction, we compared the nasopharyngeal carriage prevalence and density of Streptococcus pneumoniae (SP) and Pneumocystis jirovecii (PJ) between children living with HIV and HEU or HUU cases (pneumonia) and controls (without pneumonia). Results The cohort included 1154 children (555 cases and 599 matched controls). The SP carriage prevalence rates were similar between cases and controls. Among SP carriers with pneumonia, carriage density was increased among children living with HIV, versus HEU or HUU children (15.8, 4.7, and 3.6 × 105 copies/mL, respectively). The rate of PJ carriage was significantly higher among children living with HIV than among HEU and HUU children (31%, 15%, and 10%, respectively; P < .05), as was carriage density (63.9, 20.9, and 4.8 × 103 copies/mL, respectively; P < .05). Conclusions Carriage prevalences and densities for SP and PJ show different kinetics in terms of their relationship with HIV exposure and clinical status, particularly for Pneumocystis jirovecii. This supports the theory that the increased morbidity and mortality observed among HEU children may reflect deficits not just in humoral immunity but in cell-mediated immunity as well.

scholarly journals Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project

2021 ◽  
Vol 9 (4) ◽  
pp. 696 ◽  
Author(s):  
Julia Bennett ◽  
Marissa Hetrich ◽  
Maria Garcia Quesada ◽  
Jenna Sinkevitch ◽  
Maria Deloria Knoll ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Incidence Rate ◽  
Invasive Pneumococcal Disease ◽  
Pneumococcal Disease ◽  
Mixed Effects ◽  
Data Availability ◽  
Serotype Replacement ◽  
Serotype 1 ◽  
Pneumococcal Serotype ◽  
Rate Ratios

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for <5 years of age, 0.08 (0.06–0.09) for 5–17 years, 0.06 (0.05–0.08) for 18–49 years, 0.06 (0.05–0.07) for 50–64 years, and 0.05 (0.04–0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3 + 0 schedule constrains generalizability and data from these settings are needed.

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