Dataset Information

Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.

ABSTRACT: Streptococcus pneumonia (the pneumococcus) is the leading vaccine preventable cause of serious infections in infants under 5 years of age. The major correlate of protection for pneumococcal infections is serotype-specific IgG antibody. More recently, antibody-independent mechanisms of protection have also been identified. Preclinical studies have found that IL-17 secreting CD4+ Th17 cells in reducing pneumococcal colonisation. This study assessed IL-17A levels in children from Fiji with high and low pneumococcal carriage density, as measured by quantitative real-time PCR (qPCR). We studied Th17 responses in 54 children who were designated as high density carriers (N=27, >8.21x10(5) CFU/ml) or low density carriers (N=27, <1.67x10(5) CFU/ml). Blood samples were collected, and isolated peripheral blood mononuclear cells (PBMCs) were stimulated for 6 days. Supernatants were harvested for cytokine analysis by multiplex bead array and/or ELISA. Th17 cytokines assayed included IL-17A, IL-21, IL-22 as well as TNF-?, IL-10, TGF-?, IL-6, IL-23 and IFN?. Cytokine levels were significantly lower in children with high density pneumococcal carriage compared with children with low density carriage for IL-17A (p=0.002) and IL-23 (p=0.04). There was a trend towards significance for IL-22 (p=0.057) while no difference was observed for the other cytokines. These data provide further support for the role of Th17-mediated protection in humans and suggest that these cytokines may be important in the defence against pneumococcal carriage.

SUBMITTER: Hoe E

PROVIDER: S-EPMC4466549 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.

Hoe Edwin E Boelsen Laura K LK Toh Zheng Quan ZQ Sun Guang Wen GW Koo Ghee Chong GC Balloch Anne A Marimla Rachel R Dunne Eileen M EM Tikoduadua Lisi L Russell Fiona M FM Satzke Catherine C Mulholland E Kim EK Licciardi Paul V PV

PloS one 20150612 6

Streptococcus pneumonia (the pneumococcus) is the leading vaccine preventable cause of serious infections in infants under 5 years of age. The major correlate of protection for pneumococcal infections is serotype-specific IgG antibody. More recently, antibody-independent mechanisms of protection have also been identified. Preclinical studies have found that IL-17 secreting CD4+ Th17 cells in reducing pneumococcal colonisation. This study assessed IL-17A levels in children from Fiji with high and ...[more]

PMID: 26069966

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Project description:Importance:Pneumococcal nasopharyngeal carriage is a prerequisite for pneumococcal disease. The main transmission route is from toddlers, who commonly carry pneumococci. However, neonatal pneumococcal disease case reports suggest that vertical pneumococcal transmission may also occur. Objective:To describe and compare pneumococcal nasopharyngeal carriage and density by infant mode of delivery in young Fijian infants. Design, Setting, and Participants:Annual cross-sectional surveys were performed in Suva, Fiji, before the introduction of 10-valent pneumococcal conjugate vaccine (PCV10), from September 14 to December 20, 2012, and after PCV10 was introduced, from July 11 to November 19, 2013; July 15 to December 9, 2014; and August 13 to November 19, 2015. Caregivers of 2006 infants aged 5 to 8 weeks participated in the surveys. Statistical analysis was performed from May 24, 2018, to August 12, 2019. Exposures:Caregivers provided data on infant mode of delivery and demographics via interviewer-led survey. Main Outcomes and Measures:Pneumococci in swab samples were detected and quantified by lytA quantitative polymerase chain reaction with molecular serotyping by microarray. Pneumococci were categorized as PCV10 or non-PCV10 serotypes. Results:Of the 2006 infants (976 girls and 1030 boys; mean [SD] age, 6.1 [0.02] weeks]), 1742 (86.8%) were born vaginally and 264 were born by cesarean delivery. Infants delivered vaginally, compared with those born by cesarean delivery, had a higher prevalence of overall pneumococcal nasopharyngeal carriage (470 of 1722 [27.3%; 95% CI, 25.2%-29.4%] vs 47 of 260 [18.1%; 95% CI, 13.6%-23.3%]; P?=?.002), PCV10 carriage (113 of 1698 [6.7%; 95% CI, 5.5%-7.9%] vs 8 of 256 [3.1%; 95% CI, 1.4%-6.1%]; P?=?.03), and non-PCV10 carriage (355 of 1698 [20.9%; 95% CI, 19.0%-22.9%] vs 38 of 256 [14.8%; 95% CI, 10.7%-19.8%]; P?=?.02), and had higher median densities of overall pneumococci (4.9 log10 genome equivalents [GE]/mL [interquartile range, 4.8-5.0 log10 GE/mL] vs 4.5 log10 GE/mL [interquartile range, 4.1-4.6 log10 GE/mL]; P?=?.01) and non-PCV10 pneumococci (4.9 log10 GE/mL [interquartile range, 4.7-5.0 log10 GE/mL] vs 4.4 log10 GE/mL [interquartile range, 4.0-4.7 log10 GE/mL]; P?=?.01). Vaginal delivery was associated with overall (adjusted odds ratio, 1.57 [95% CI, 1.10-2.23]; P?=?.01) and non-PCV10 (adjusted odds ratio, 1.49 [95% CI, 1.01-2.20]; P?=?.04]) pneumococcal nasopharyngeal carriage. Vaginal delivery was not associated with PCV10 carriage (adjusted odds ratio, 1.67 [95% CI, 0.80-3.51]; P?=?.17). After adjustment, vaginal delivery was not associated with density. Conclusions and Relevance:Pneumococcal nasopharyngeal carriage prevalence and density were higher in infants delivered vaginally compared with those delivered by cesarean birth. After adjustment, vaginal delivery was associated with pneumococcal carriage. Differences in carriage by mode of delivery may be due to differential exposure to the vaginal microbiota during delivery and the effect of intrapartum antibiotics during cesarean delivery on the infant microbiome. Our findings also raise the hypothesis that vertical transmission may contribute to pneumococcal acquisition.

Project description:Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23vPPV in children under two years of age are appropriate.

Dataset Information

Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.

Publications

Reduced IL-17A Secretion Is Associated with High Levels of Pneumococcal Nasopharyngeal Carriage in Fijian Children.

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