Nasopharyngeal colonization dynamics with Streptococcus pneumoniae and associated antimicrobial-resistance in a South African birth cohort.
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PROVIDER: PRJEB37312 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR4181510_1.fastq.gz | Fastqsanger.gz | |||
| ERR4181510_2.fastq.gz | Fastqsanger.gz | |||
| ERR4181520_1.fastq.gz | Fastqsanger.gz | |||
| ERR4181520_2.fastq.gz | Fastqsanger.gz | |||
| ERR4181530_1.fastq.gz | Fastqsanger.gz |
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Project description:Introduction: Nasopharyngeal (NP) colonization by Streptococcus pneumoniae (pneumococcus) precedes the development of respiratory tract infection. Colonization by antimicrobial-resistant pneumococci, especially in infants, is a major public health concern. We longitudinally investigated antimicrobial-resistance amongst pneumococci colonizing the nasopharynx of South African infants immunized with the 13-valent pneumococcal conjugate vaccine (PCV13). Methods: NP swabs were collected every second week from birth through the first year of life from 137 infants. Pneumococci were identified and serotyped using conventional microbiological techniques, and their antibiotic susceptibility profiles determined by disk diffusion and E-test. Results: All infants were immunized with 3 doses of PCV13. 1520 pneumococci (760 non-repeat) isolates were recovered from 137 infants; including non-typeable (n = 99), PCV13 (n = 133) and non-PCV13 serotypes (n = 528). The prevalence of penicillin, erythromycin, and cotrimoxazole non-susceptibility was 19% (95% CI 17-22%) (3% fully resistant), 18% (95% CI 15-21%) (14% fully resistant), and 45% (95% CI 42-49%) (36% fully resistant), respectively. The predominant penicillin-non-susceptible serotypes included 19A, 19F, 15B/15C, 15A, and 21, while susceptible serotypes included 23A, 34, and 17A. Multidrug-resistance (MDR) was observed in 9% (95% CI 7-11%) of the isolates. PCV13 serotypes were more likely to be non-susceptible, compared to non-PCV13 serotypes, to penicillin (26% vs. 16%, p = 0.007), erythromycin (23% vs. 15%, p = 0.027) and cotrimoxazole (62% vs. 41%, p < 0.001). Non-susceptibility to penicillin, erythromycin, and cotrimoxazole remained relatively constant through the first year of life (X 2 test for trend: p = 0.184, p = 0.171, and p = 0.572, respectively). Overall, penicillin or erythromycin-non-susceptible pneumococci were carried for a shorter duration than susceptible pneumococci [penicillin (mean days, 18 vs. 21, p = 0.013) and erythromycin (mean days, 18 vs. 21, p = 0.035)]. Within individual infants carrying the same serotype longitudinally, changes in antibiotic susceptibility were observed over time in 45% (61/137) of infants and these changes were predominantly for penicillin (76%, 79/104). Conclusion: Prevalence of NP carriage with antibiotic-non-susceptible pneumococci was relatively constant throughout the first year of life. PCV13 serotypes were more commonly non-susceptible to penicillin, erythromycin, and cotrimoxazole. Penicillin or erythromycin-non-susceptible pneumococci were carried for a shorter duration than penicillin or erythromycin-susceptible pneumococci.
| S-EPMC6446970 | biostudies-literature
Project description:Background: There remains a significant proportion of deaths due to pneumococcal pneumonia in infants from low- and middle-income countries despite the marginal global declines recorded in the past decade. Monitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage, patterns of antimicrobial resistance, and impact on health. We longitudinally investigated pneumococcal carriage dynamics in PCV-13 vaccinated infants by collecting nasopharyngeal (NP) samples at 2-weekly intervals from birth through the first year of life from 137 infants. As a proof of concept, 196 NP samples were retrieved from a subset of 23 infants to explore strain-level pneumococcal colonization patterns and associated antimicrobial-resistance determinants. These were selected on the basis of changes in serotype and antibiogram over time. NP samples underwent short-term enrichment for streptococci prior to total nucleic acid extraction and whole metagenome shotgun sequencing (WMGS). Reads were assembled and aligned to pneumococcal reference genomes for the extraction of pneumococcal and non-pneumococcal bacterial reads. Pneumococcal contigs were aligned to the Antibiotic Resistance Gene-ANNOTation database of acquired AMR genes. In silico pneumococcal capsular and multilocus sequence typing were performed. Results: Of the 196 samples sequenced, 174 had corresponding positive cultures for pneumococci, of which, 152 were assigned an in silico serotype. Metagenomic sequencing detected a single pneumococcal serotype in 85% (129/152), and co-colonization in 15% (23/152) of the samples. Twenty-two different pneumococcal serotypes were identified, with 15B/15C and 16F being the most common non-PCV13 serotypes, while 23F and 19A were the most common PCV13 serotypes. Twenty-six different sequence types (STs), including four novel STs were identified in silico. Mutations in the folA and folP genes, associated with cotrimoxazole resistance, were detected in 89% (87/98) of cotrimoxazole-non-susceptible pneumococci, as well as in the pbp1a and pbp2x genes, in penicillin non-susceptible ST705215B/15C isolates. Conclusions: Metagenomic sequencing of NP samples is a valuable culture-independent technique for a detailed evaluation of the pneumococcal component and resistome of the NP microbiome. This method allowed for the detection of novel STs, as well as co-colonization, with a predominance of non-PCV13 serotypes in this cohort. Forty-eight resistance genes, as well as mutations associated with resistance were detected, but the correlation with phenotypic non-susceptibility was lower than expected.
| S-EPMC7536305 | biostudies-literature
Project description:Streptococcus pneumoniae is a frequent coloniser of the human nasopharynx and a major cause of life-threating invasive infections such as pneumonia, meningitis and sepsis. Over 1 million people die every year due to invasive pneumococcal disease (IPD), mainly in developing countries. Serotype 1 is a common cause of IPD; however, unlike other serotypes, it is rarely found in the carrier state in the nasopharynx, which is often considered a prerequisite for disease. The aim of this study was to understand this dichotomy. We used murine models of carriage and IPD to characterise the pathogenesis of African serotype 1 (Sequence Type 217) pneumococcal strains obtained from the Queen Elizabeth Central Hospital in Blantyre, Malawi. We found that ST217 pneumococcal strains were highly virulent in a mouse model of invasive pneumonia, but in contrast to the generally accepted assumption, can also successfully establish nasopharyngeal carriage. Interestingly, we found that co-colonising serotypes may proliferate in the presence of serotype 1, suggesting that acquisition of serotype 1 carriage could increase the risk of developing IPD by other serotypes. RNAseq analysis confirmed that key virulence genes associated with inflammation and tissue invasiveness were upregulated in serotype 1. These data reveal important new insights into serotype 1 pathogenesis, with implications for carriage potential and risk of invasive disease through interactions with other co-colonising serotypes; an often overlooked factor in transmission and disease progression.
2020-11-12 | GSE159305 | GEO
Project description:Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights. RNA from umbilical cord tissue from full term neonates was extracted and hybridized. Separation into 2 distinct groups, independent of birth weight, but based solely on gene expression levels was analysed by Genespring. After appropriate statistical analysis, one group was keenly associated with a higher birth weight (22 samples) while the other was associated with a lower birth-weight (18 samples). Technical replicates were included for all 40 samples.
2011-10-20 | E-GEOD-24818 | biostudies-arrayexpress
Project description:Sub-optimal fetal development is associated with an increased risk of developing cardiovascular disease, type 2 diabetes (T2D) and adiposity later in life. However, definitions of intrauterine growth restriction (IUGR) and small for gestational age (SGA) are based on simple statistical approaches that may misclassify infants with a normal developmental profile and vice versa. We used an unbiased global profiling approach to identify gene expression patterns in umbilical cord tissue from 38 infants and identified a set of 466 genes which separated the subjects into 2 distinct groups – one biased towards lower birth weight and one biased towards normal birth weight. The data suggest that approximately 30% of children of normal size have a molecular profile more typical of impaired fetal development and who may be on a programmed trajectory. Differences in expression between the two groups encompassed 384 upregulated and 82 downregulated genes. Molecular profiling at birth may have utility in identifying markers that potentially reflect antenatal developmental and may be predictive of future phenotypic development after birth. Importantly, it may provide an alternative to the current classification of infants using birth weights.
2011-10-21 | GSE24818 | GEO
Project description:Monitoring changes in pneumococcal carriage is key to understanding vaccination-induced shifts in the ecology of carriage and impact on health. We longitudinally investigated pneumococcal carriage dynamics in infants. Pneumococcal isolates were obtained from nasopharyngeal (NP) swabs collected 2-weekly from 137 infants enrolled from birth through their first year of life. Pneumococci were serotyped by sequetyping, confirmed by Quellung. Pneumococci were isolated from 54% (1809/3331) of infants. Median time to first acquisition was 63 days. Serotype-specific acquisition rates ranged from 0.01 to 0.88 events/child-year and did not differ between PCV13 and non-PCV13 serotypes (0.11 events/child-year [95% CI 0.07-0.18] vs. 0.11 events/child-year [95% CI 0.06-0.18]). There was no difference in carriage duration between individual PCV13 and non-PCV13 serotypes (40.6 days [95% CI 31.9-49.4] vs. 38.6 days [95% CI 35.1-42.1]), however cumulatively the duration of carriage of non-PCV13 serotypes was greater than PCV13 serotypes (141.2 days (95% CI 126.6-155.8) vs. 30.7 days (95% CI 22.3-39.0). Frequently carried PCV13 serotypes included 19F, 9V, 19A and 6A, while non-PCV13 serotypes included 15B/15C, 21, 10A, 16F, 35B, 9N and 15A. Despite high immunization coverage in our setting, PCV13 serotypes remain in circulation in this cohort, comprising 22% of isolates. Individual PCV13 serotypes were acquired, on average, at equivalent rate to non-PCV13 serotypes, and carried for a similar duration, although the most common non-PCV13 serotypes were more frequently acquired than PCV13 serotypes.
| S-EPMC6104038 | biostudies-literature
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 Whole blood collected 1 day post-vaccination with MVA85A or Candin placebo (82 samples)
2014-06-11 | E-GEOD-56559 | biostudies-arrayexpress
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927
2014-06-11 | GSE56559 | GEO
Project description:Background: Tuberculosis (TB) remains a global health problem, with vaccination likely to be a necessary part of a successful control strategy. Results of the first Phase 2b efficacy trial of a candidate vaccine, MVA85A, evaluated in BCG-vaccinated infants were published last year. Although no improvement in efficacy above BCG alone was seen, cryopreserved samples from this trial provide an opportunity to study the immune response to vaccination in this population. Methods: We investigated blood samples taken before vaccination (baseline) and one and 28 days post-vaccination with MVA85A or placebo (Candin). The IFN-γ ELISpot assay was performed at baseline and on day 28 to quantify the adaptive response to Ag85A peptides. Gene expression analysis was performed at all three timepoints to identify early gene signatures predictive of the magnitude of the subsequent adaptive T cell response using the significance analysis of microarrays (SAM) statistical package and gene set enrichment analysis. Results: One day post-MVA85A, there is an induction of inflammatory pathways compared to placebo samples. Modules associated with myeloid cells and inflammation pre- and one day post-MVA85A correlate with a higher IFN-γ ELISpot response post-vaccination. By contrast, previous work done in UK adults shows early inflammation in this population is not associated with a strong T cell response but that induction of regulatory pathways inversely correlates with the magnitude of the T cell response. This may be indicative of important mechanistic differences in how T cell responses develop in these two populations following vaccination with MVA85A. Conclusion: The results suggest the capacity of MVA85A to induce a strong innate response is key to the initiation of an adaptive immune response in South African infants but induction of regulatory pathways may be more important in UK adults. Understanding differences in immune response to vaccination between populations is likely to be an important aspect of developing successful vaccines and vaccination strategies. Trial registration: ClinicalTrials.gov number NCT00953927 PBMC collected pre or 28 days post vaccinated, stimulated with either Ag85A peptides (20 samples) or media alone (60).
2014-06-11 | E-GEOD-56561 | biostudies-arrayexpress