Dataset Information

Use of Multiplex Quantitative PCR To Evaluate the Impact of Pneumococcal Conjugate Vaccine on Nasopharyngeal Pneumococcal Colonization in African Children.

ABSTRACT: Pneumococcal conjugate vaccine (PCV) immunization of children induces shifts in colonizing pneumococcal serotypes. This study evaluated the effect of infant vaccination with 7-valent PCV (PCV7) on vaccine serotype (VT) colonization and whether the increase in nonvaccine serotype (NVT) was due to either unmasking of previously low-density-colonizing serotypes or increase in acquisition of NVT. A multiplex quantitative PCR (qPCR) was used to evaluate VT and NVT nasopharyngeal colonization in archived swabs of PCV-vaccinated and PCV-unvaccinated African children at 9 and 15 to 16 months of age. Molecular qPCR clearly identified the vaccine effect typified by a decrease in VT colonization and an increase in NVT colonization. Serotype 19A was primarily responsible for the higher NVT carriage among PCV vaccinees at 9 months of age (53.4% difference; P = 0.021) and 16 months of age (70.7% difference; P < 0.001). Furthermore, the density of serotype 19A colonization was higher in PCV-vaccinated groups than in PCV-unvaccinated groups (3.76 versus 2.83 CFU/ml [P = 0.046], respectively, and 4.15 versus 3.04 CFU/ml [P = 0.013], respectively) at 9 and 16 months of age, respectively. Furthermore, serotype 19A was also more commonly reported as a primary isolate (by having the highest density among other cocolonizing serotypes identified in the sample) in PCV7-vaccinated children, while being equally a primary (46.2%) or nonprimary (53.8%) isolate in PCV-unvaccinated children. Molecular qPCR showed both serotype replacement and unmasking to be the cause for the increase in NVT colonization in PCV7-vaccinated children, as some serotypes were associated with an absolute increase in colonization (replacement), while others were associated with an increase in detection (unmasking). IMPORTANCE This study focused on evaluating the effect of infant vaccination with 7-valent pneumococcal conjugate vaccine (PCV7), using a multiplex qPCR method, on the density of serotype-specific nasopharyngeal colonization in order to delineate the relative role of serotype replacement versus unmasking as the cause for the increase in nonvaccine serotype colonization in PCV7-vaccinated children. This is pertinent in the context of the ongoing deployment of PCV immunization in children, with surveillance of colonization considered an early proxy for disease that might arise from nonvaccine serotypes, as well as the success of childhood vaccination on indirect effect in the community through the interruption of pneumococcal transmission from vaccinated young children.

SUBMITTER: Olwagen CP

PROVIDER: S-EPMC5677981 | biostudies-literature | 2017 Nov-Dec

REPOSITORIES: biostudies-literature

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Use of Multiplex Quantitative PCR To Evaluate the Impact of Pneumococcal Conjugate Vaccine on Nasopharyngeal Pneumococcal Colonization in African Children.

Olwagen Courtney P CP Olwagen Courtney P CP Adrian Peter V PV Nunes Marta C MC Groome Michelle J MJ Cotton Mark F MF Violari Avy A Madhi Shabir A SA

mSphere 20171108 6

Pneumococcal conjugate vaccine (PCV) immunization of children induces shifts in colonizing pneumococcal serotypes. This study evaluated the effect of infant vaccination with 7-valent PCV (PCV7) on vaccine serotype (VT) colonization and whether the increase in nonvaccine serotype (NVT) was due to either unmasking of previously low-density-colonizing serotypes or increase in acquisition of NVT. A multiplex quantitative PCR (qPCR) was used to evaluate VT and NVT nasopharyngeal colonization in archi ...[more]

PMID: 29134203

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Project description:Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n?=?173), unvaccinated children of the vaccine era (n?=?169), and fully vaccinated children (4 doses; n?=?150). Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p?=?0.004; Fisher's exact test) among fully vaccinated children (8.0%) than among children from the pre-PCV7 era (17.3%) or unvaccinated children of the PCV7 era (18.3%). In the PCV7 era there were significantly less non-vaccine type (NVT) co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p?=?0.024). In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering pneumococcal evolution events such as acquisition of antibiotic resistance determinants or capsular switch. This might represent a novel potential benefit of conjugate vaccines.

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:Streptococcus pneumoniae (pneumococcus) remains an important cause of morbidity and mortality. Pneumococcal vaccination is part of the South African pediatric public immunization program but the potential cost-effectiveness of such an intervention for adults is unknown. This study aimed to compare the cost-effectiveness of two widely used pneumococcal vaccines: pneumococcal conjugate vaccine (PCV13) and pneumococcal polysaccharide vaccine (PPSV23) in South African adults, 18 years and older. Four analyses were carried out in a) both the private and public health care sectors; and b) for the HIV-infected population alone and for the total mixed population (all HIV-infected and -uninfected people). A previously published global pharmacoeconomic model was adapted and populated to represent the South African adult population. The model utilized a Markov-type process to depict the lifetime clinical and economic outcomes of patients who acquire pneumococcal disease in 2015, from a societal perspective. Costs were sourced in South African rand and converted to US dollar (USD). The incremental cost divided by the incremental effectiveness (expressed as quality-adjusted life years gained) represented the incremental cost-effectiveness ratio for PCV13 compared to PPSV23. Results indicated that the use of PCV13 compared to PPSV23 is highly cost-effective in the public sector cohorts with incremental cost-effectiveness ratios of $771 (R11,106)/quality-adjusted life year and $956 (R13,773)/quality-adjusted life year for the HIV-infected and mixed populations, respectively. The private sector cohort showed similar highly cost-effective results for the mixed population (incremental cost-effectiveness ratio $626 (R9,013)/quality-adjusted life year) and the HIV-infected cohort (dominant). In sensitivity analysis, the model was sensitive to vaccine price and effectiveness. Probabilistic sensitivity analyses found predominantly cost-effective ICERs. From a societal perspective, these findings provide some guidance to policy makers for consideration and implementation of an immunization strategy for both the public and private sector and amongst different adult patient pools in South Africa.

Dataset Information

Use of Multiplex Quantitative PCR To Evaluate the Impact of Pneumococcal Conjugate Vaccine on Nasopharyngeal Pneumococcal Colonization in African Children.

Publications

Use of Multiplex Quantitative PCR To Evaluate the Impact of Pneumococcal Conjugate Vaccine on Nasopharyngeal Pneumococcal Colonization in African Children.

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