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Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

ABSTRACT: Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose on serotype quantitative and qualitative antibody responses.Colonization prior to receiving the first PCV was associated with lower geometric mean antibody concentrations (GMCs) one month after the third dose of PCV and six months later to the colonizing-serotype. Colonized infants also had lower geometric mean titers (GMTs) on opsonophagocytosis activity assay (OPA) and a lower proportion had titers ? 8 against the colonizing serotypes (19F and 23F) post vaccination. Colonization occurring only prior to the 2nd/3rdPCV dose was also associated with lower GMCs and OPA GMTs to the colonizing-serotype. The effect of colonization with serotypes 19F and 23F prior to PCV vaccination had a greater effect on a lower proportion of colonized infants having OPA titers ? 8 than the effect of colonization on the lower proportion with antibody ? 0.35 ?g/ml.Infant nasopharyngeal colonization at any stage before completing the primary series of PCV vaccination was associated with inferior quantitative and qualitative antibody responses to the colonizing-serotype.

SUBMITTER: Madhi SA

PROVIDER: S-EPMC3167924 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

Madhi Shabir A SA Violari Avy A Klugman Keith P KP Lin Gina G McIntyre James A JA von Gottberg Anne A Jean-Philippe Patrick P Cotton Mark F MF Adrian Peter P

Vaccine 20110723 40

<h4>Background</h4>Heightened immunogenicity, measured one month after the primary series of pneumococcal conjugate vaccine (PCV), in African children was previously hypothesized to be due to increased rates of nasopharyngeal pneumococcal colonization during early infancy.<h4>Methods</h4>We analyzed the effect of selected vaccine-serotype (6B, 19F and 23F) nasopharyngeal colonization prior to the first PCV dose or when colonized for the first time prior to the second or third (2nd/3rd) PCV dose ...[more]

PMID: 21787822

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Project description:BackgroundWe describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic-resistant pneumococci in urban Alaskan children during 2000-2010.MethodsWe obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000-2004 and 2008-2010. PCV7 status and antibiotic use <90 days before enrollment were determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS.ResultsWe recruited 3496 children (median, 452 per year). During 2000-2010, a range of 18-29% per year of children used PCN/amoxicillin (P value for trend = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0[FIGURE DASH]90%; P < 0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53-<1%; P < 0.01) and non[FIGURE DASH]PCV7-serotype proportion increased (43-95%; P < 0.01). PCN-R pneumococcal colonization prevalence decreased (23-9%; P < 0.01) and PCN-I pneumococcal colonization prevalence increased (13-24%; P < 0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non[FIGURE DASH]PCV7-type pneumococci remained unchanged; a mean of 31% per year of PCV7-type and 10% per year of non[FIGURE DASH]PCV7-type isolates were PCN-R, and 10% per year of PCV7 and 20% per year of non[FIGURE DASH]PCV7-type isolates were PCN-I.ConclusionsOverall, PCN-NS pneumococcal colonization remained unchanged during 2000-2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype groups (PCV7 vs. non-PCV7) despite stable PCN use in our population.

Project description:BackgroundReduced-dose pneumococcal conjugate vaccine (PCV) schedules are under consideration in countries where children are recommended to receive 3 doses. Whereas PCV-derived protection against vaccine-serotype colonization is responsible for herd effects of vaccination, dose-specific PCV effectiveness against colonization endpoints is not known. We aimed to assess the performance of differing PCV schedules against vaccine-serotype colonization in children.MethodsFrom 2009-2016, we monitored pneumococcal carriage in southern Israel, where children should receive PCV at ages 2 months, 4 months, and 12 months (2 primary [p] +1 booster [b] schedule). We analyzed nasopharyngeal swabs and vaccination histories from 5928 children aged 0-59 months without symptoms of diseases potentially attributable to pneumococci. Matching individuals on age, sex, ethnicity, visit timing, and recent antibiotic receipt, we measured schedule-specific 7-valent PCV (PCV7) and 13-valent PCV (PCV13) effectiveness against vaccine-serotype colonization in a modified case-control framework. We sampled from the distribution of all possible case-control match assignments for statistical analyses.ResultsReceiving 2 primary-series PCV13 doses conferred 53% (95% confidence interval [CI], 32-67%) protection against PCV13-serotype colonization at ages ≤12 months; 1 primary-series dose was not protective. A 2p+1b PCV13 series conferred 40% (95% CI, 4-67%) and 62% (95% CI, 33-83%) protection against PCV13-serotype colonization at ages 13-24 months and 25-59 months, respectively. Estimates suggested greater PCV13-conferred protection against PCV7-targeted serotypes than the 6 PCV13-only serotypes. As compared to children receiving 2p+1b PCV13 dosing, those receiving 1p+1b and 2p+0b schedules experienced 2.05-fold (95% CI, 1.12-5.00) and 3.33-fold (95% CI, 2.28-4.93) greater odds, respectively, of vaccine-serotype pneumococcal colonization at ages 13-24 months.ConclusionsOur results demonstrate real-world effectiveness of 2p+1b PCV dosing against vaccine-serotype colonization. Reduced-dose schedules may confer lower protection against vaccine-serotype carriage during and beyond the first year of life.

Project description:BackgroundStreptococcus pneumoniae is a major cause of pneumonia, meningitis, and other serious infections among children in India. India introduced the 13-valent pneumococcal conjugate vaccine (PCV) in several states in 2017, and is expected to expand to nationwide coverage in the near future. To establish a baseline for measuring the impact of PCV in India, we assessed overall and serotype-specific nasopharyngeal carriage in two pediatric populations.MethodsA cross-sectional study was conducted in Palwal District, Haryana, from December 2016 to July 2017, prior to vaccine introduction. Children 2-59 months of age with clinical pneumonia seeking healthcare and those in the community with no clear illness were targeted for enrollment. A nasopharyngeal swab was collected and tested for pneumococcus using conventional culture and sequential multiplex PCR. Isolates were tested for antimicrobial resistance using an E test. Children were considered colonized if pneumococcus was isolated by culture or PCR. The prevalence of pneumococcal and serotype-specific colonization was compared between groups of children using log-binomial regression.ResultsAmong 601 children enrolled, 91 had clinical pneumonia and 510 were community children. The proportion colonized with S. pneumoniae was 74.7 and 54.5% among children with clinical pneumonia and community children, respectively (adjusted prevalence ratio: 1.38; 95% confidence interval: 1.19, 1.60). The prevalence of PCV13 vaccine-type colonization was similar between children with clinical pneumonia (31.9%) and community children (28.0%; p = 0.46). The most common colonizing serotypes were 6A, 6B, 14, 19A, 19F, and 23F, all of which are included in the PCV13 vaccine product. Antimicrobial resistance to at least one drug was similar between isolates from children with clinical pneumonia (66.1%) and community children (61.5%; p = 0.49); while resistance to at least two drugs was more common among isolates from children with clinical pneumonia (25.8% vs. 16.4%; p = 0.08). Resistance for all drugs was consistently higher for PCV13 vaccine-type serotypes compared to non-vaccine serotypes in both groups.ConclusionThis study provides baseline information on the prevalence of serotype-specific pneumococcal colonization among children prior to the introduction of PCV in India. Our results suggest a role for pneumococcal vaccines in reducing pneumococcal colonization and antimicrobial resistant isolates circulating in India.

Dataset Information

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

Publications

Inferior quantitative and qualitative immune responses to pneumococcal conjugate vaccine in infants with nasopharyngeal colonization by Streptococcus pneumoniae during the primary series of immunization.

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