Conjugate Vaccine Era Research Articles

Prevention of pneumococcal infections in childhood: two decades of progress.

This review highlights progress in combating pediatric pneumococcal disease in the era of pneumococcal conjugate vaccines (PCVs). This review is timely given the development of increased valency PCVs for potential use in children. Countries implementing vaccination programs with PCVs have witnessed dramatic reductions in cases of childhood invasive pneumococcal disease (IPD). In the US, the largest decline of IPD followed the introduction of 7-valent PCV with additional decreases following the switch to 13-valent PCV (PCV13). Despite these gains, IPD still occurs in the US but at much lower rates. Likewise, pneumonia hospitalizations and office visits for otitis media have decreased. Nasopharyngeal colonization with pneumococci has persisted due to replacement by nonvaccine serotypes: colonizing non-PCV13 serotypes have less invasive potential. The PCV era has also been marked by reductions in the proportions of pneumococcus showing nonsusceptibility or resistance to some antimicrobial agents. Furthermore, PCVs have an excellent safety profile. Despite proven safety and efficacy, childhood vaccination programs in some countries do not include PCVs, resulting in the majority of global deaths attributable to pneumococcus. Increased worldwide vaccination of children and the development of higher valency vaccines holds additional promise for further reductions in childhood IPD.

Clinical pneumonia in the hospitalised child in Malawi in the post-pneumococcal conjugate vaccine era: a prospective hospital-based observational study

ObjectiveAssess characteristics of clinical pneumonia after introduction of pneumococcal conjugate vaccine (PCV), by HIV exposure status, in children hospitalised in a governmental hospital in Malawi.Methods and findingsWe evaluated 1139 children...

Aetiology and presentation of childhood pleural infections in the post-pneumococcal conjugate vaccine era in South Africa.

Background Complications of respiratory infections including pleural effusion (PE) are associated with a high morbidity. Differentiating between PE caused by Mycobacterium tuberculosis (Mtb) infection and other bacterial infections in endemic areas is difficult in children, thus, impacting treatment. Objectives To investigate the aetiology of PE and features distinguishing tuberculosis (TB) from bacterial PE in children. Methods We conducted a prospective study in children with PE admitted to a tertiary hospital in Cape Town from December 2017 to December 2019. Clinical information and routine laboratory investigations were compared between children with bacterial, Mtb or unclassified PE, categorised according to study definitions. Results A total of 91 patients were included in the present study and their median age was 31 months (interquartile range (IQR) 11.8 - 102.1). The aetiology was bacterial in 40% (n=37), Mtb in 39% (n=36) and unclassified in 20% (n=18) of patients. Staphylococcus aureus was the most common bacterial isolate, confirmed in 65% (n=24/37) patients, and Streptococcus pneumoniae was confirmed in only 8% of patients. TB was microbiologically confirmed in 33% (n=12/36) of patients. Patients with TB were older (91.6 v. 11.8 months; p<0.001), with more weight loss (28 v. 12 patients; p<0.001), and longer cough duration (10 v. 4 days; p<0.001) than those with other bacterial PE. In contrast, the latter had significantly higher serum C-reactive protein (median 250 v. 122 mg/L; p<0.001), procalcitonin (11 v. 0.5 mg/L; p<0.001), pleural fluid lactate dehydrogenase (7 280 v. 544 U/L; p<0.001), and adenosine deaminase levels (162 v. 48 U/L; p<0.001) and lower glucose levels (1.3 v. 4 mmol/L; p<0.001). Conclusion Post 13-valent pneumococcal conjugate vaccine, S. aureus is the dominant cause of PE in children using traditional culture methods, while Mtb remains a common cause of PE in our setting. Useful clinical and laboratory differences between Mtb and other bacterial PE were identified, but the cause of PE in 20% of children was underdetermined. Molecular testing of pleural fluid for respiratory pathogens may be useful in such children.

Pneumococcal Serotype Identification by Capsular Sequence Typing (CST): A Modified Novel Approach for Serotyping Directly in Clinical Samples.

As almost 60–70% of Invasive Pneumococcal Disease (IPD) is identified by nonculture methods in Greece, serotyping is of high importance for the better monitoring of pneumococcal serotypes due to the availability of conjugate vaccines. The aim of the study was the modification and direct application of the Capsular Sequence Typing (CST) assay in clinical samples in order to serotype Streptococcus pneumoniae culture-negative, Polymerase Chain Reaction (PCR_-positive samples, followed by CST group specific single-tube PCR assays. A two-step PCR modified assay was applied on a total of 306 samples (such as CSF, blood, pleural and middle ear fluids, isolates) obtained from 283 patients with IPD. The overall performance permits a rapid, accurate and cost-effective method for nonculture pneumococcal serotyping. As the management of IPD is closely related to the continuous monitoring of pneumococcal serotypes, the proposed approach proved to be a valuable tool for the typing and epidemiological monitoring of S. pneumoniae, for the evaluation of the overall impact of vaccination programs in the era of pneumococcal conjugate vaccines, in order to initiate the appropriate vaccination strategy.

Serotypes in Adult Pneumococcal Pneumonia in Spain in the Era of Conjugate Vaccines

We studied changes in serotype distribution and antimicrobial susceptibility in adult pneumococcal pneumonia in Spain (2011–2019). Among 895 pneumococci collected (433 bacteremic [BPP] and 462 non-bacteremic [non-BPP]), serotypes 3 (17%), 19A (10%), 8 (6.7%) and 11A (6.7%) were the most frequent. Serotypes 16F, 19A and 24F were associated with old people (≥65) and serotypes 4, 7F, 8, 12F and 19F to young adults. Serotypes 12F, 24F and 1 were significantly more frequent in BPP and serotypes 11A, 23A and 19F in non-BPP. Amoxicillin resistance was higher in non-BPP (17% vs. 11%) while penicillin non-susceptibility (37% vs. 24%) and macrolide resistance (29% vs. 14%) were higher in older adults. In the period 2017–2019, the vaccine coverages were: 32% (PCV13), 39% (PCV15), 65% (PCV20) and 69% (PPV23). Differences were found in serotype composition and antimicrobial resistance by age and type of infection. The maintenance of serotype 3 as a leading cause of adult pneumococcal pneumonia and the increase in highly invasive (serotype 8) or antimicrobial-resistant (serotype 11A) serotypes is worrisome. Further studies will be required to analyse the impact of the upcoming broader conjugate vaccines.

Occult bacteremia in children with simple febrile seizure in the post-pneumococcal conjugate vaccine era

Purpose: The authors aimed to investigate the utility of blood culture (BC) for children with simple febrile seizure (SFS) in the emergency department (ED) in the post-10/13-valent pneumococcal conjugate vaccine (PCV) era. Methods: This study was performed at the ED of a tertiary care university-affiliated women and children’s hospital, and involved 3,237 previously healthy children aged 6-60 months who visited the ED with SFS from January 2013 through December 2017. The SFS was defined according to the International Classification of Diseases, 11th Revision codes related to seizure. The children were divided into 2 groups according to the vaccination rates of the period of their visit: the 70-PCV (70%, 2013-2014) and 97-PCV (97%, 2015-2017) groups. The primary outcome was the yield, defined as a true positivity of BC. In addition, we collected information on baseline characteristics, ED length of stay, inflammatory biomarkers, and ED outcomes. Results: Of the 1,578 children with SFS who underwent BC, 1,357 belonged to the 97-PCV group. The median age of the study population was 22 months (interquartile range, 16.0-30.0), and 935 children (59.3%) were boys. Of the 41 children (2.6%) with positive BC results, 3 had the yield (0.2%): Staphylococcus aureus in 2 children and Streptococcus pneumoniae in the other. All 3 children belonged to the 97-PCV group. There were 38 contaminated BCs (2.4%; 95% confidence interval, 1.6%-3.2%). The 97-PCV group showed a shorter median ED length of stay (166.0 minutes [108.0-279.5] vs. 143.0 [109.5-209.5]; P = 0.010) and a lower rate of hospitalization (39.4% vs. 12.8%; P &lt; 0.001). No differences between the 2 groups were found in the baseline characteristics and biomarkers.Conclusion: This study suggests a low utility of BC in previously healthy children with SFS in emergency settings in the post-10/13-valent PCV era.

PCR and Culture Analysis of Streptococcus pneumoniae Nasopharyngeal Carriage in Healthy Children.

Invasive Streptococcus pneumoniae disease is preceded by asymptomatic nasopharyngeal carriage. Measuring carriage in healthy populations provides data on what serotypes are present in communities, which is of interest in the era of polyvalent pneumococcal conjugate vaccines. Nasopharyngeal swabs from a survey of 682 and 800 healthy children in 2016 and 2018, respectively, were analyzed by culture and Quellung reaction to determine rates of carriage and serotypes. All swabs from 2016 and 300 randomly selected swabs from 2018 were then analyzed using real-time semi-quantitative PCR (qPCR) to detect S. pneumoniae gene targets lytA, piaA, and SP2020 and determine serotype. There were 71 (10.4%) and 68 (8.5%) culture positive samples in 2016 and 2018, respectively. All of these were also positive by qPCR except one that was equivocal. In total, 46.0% of 2016 swabs were positive by qPCR. In 2018, results from the selected sample extrapolated to the complete sample showed 49.0% positive by qPCR. PCV13 serotypes were detected in 29.3% and 21.7% of S. pneumoniae qPCR positive samples from 2016 and 2018, respectively; compared with only 8.4% and 6.0% PCV13 serotypes detected by Quellung reaction in culture positive samples. Compared with culture, qPCR detected S. pneumoniae more frequently. Further, qPCR serotyping detected PCV13 serotypes in a larger proportion of samples than culture and Quellung reaction did, showing that, despite established universal childhood PCV13 immunization, vaccine serotypes can still be detected in a large proportion of young children.

Nasopharyngeal carriage, serotype pattern and antimicrobial non-susceptibilities of Streptococcus pneumoniae among healthy children in the 13-valent pneumococcal conjugate vaccine era in Barbados, one of the Caribbean countries

BackgroundBarbados like other countries in the English-speaking Caribbean introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in late 2007, replaced by the 13-valent vaccine (PCV13) in 2013, using a 3+ 0 dosing schedule. We investigated the prevalence and serotype pattern of nasopharyngeal (NP) carriage of Streptococcus pneumoniae (SP) and the Antimicrobial Non-susceptibility of SP (ANSP) among children. Materials and methodsA cross sectional survey of NP carriage. NP swabs were collected from healthy children (6 months to 10 years) attending the well-child clinic at the polyclinics, after parental consent, during 2016–2017. Samples were cultured for SP and isolates were serotyped by the capsular swelling method using commercial group- and type-specific sera. Susceptibility testing was conducted by broth microdilution MIC determination, according to CLSI recommended breakpoints. ResultsPrevalence of NP carriage of SP among 198 healthy children, 88.9% immunized for PCV, was 12.6% (95% CI=8.5%, 18.3%). Prevalence of NP carriage for the VT and NVT was 7.1% (95% CI=4.1%, 11.8%) and 5.6% (95%CI=3.0%, 10.0%) respectively. Serotype 19F was the most common NP isolate in 7 (28%; 12.9%, 49.6%) children and this was followed by 15B/C (25%), 35B (12%) and 6B (12.5%). More than 50% of isolates exhibited Antimicrobial Non-sensitive SP (ANSP) to Penicillin (Oral), Azithromycin and Co-trimoxazole. Serotypes 19F, 19A and 23F showed high level ANSP to 10/11 commonly used antibiotics. ConclusionsNP carriage of SP among healthy children immunized with PCV continues to be predominantly VT and exhibit high ANSP.

Estimating the risk of recurrent invasive pneumococcal disease in Australia, 1991–2016

BackgroundIndividuals who experience an initial episode of invasive pneumococcal disease (IPD) are at increased risk of recurrent episodes. However, the magnitude of risk has not been well-quantified in the pneumococcal conjugate vaccine era. Individuals with a previous episode of IPD are not commonly identified as a high-risk group in vaccination guidelines. MethodsAustralian residents with at least one case of IPD between 1991 and 2016 were identified using routine public health surveillance data which included identified IPD risk factors. Incidence of recurrent IPD was calculated from 2001 onwards (after IPD became nationally notifiable) using time-to-event analyses with individuals contributing person-time at risk of recurrence if they survived greater than 14 days after initial episode onset. ResultsFrom 1991 to 2016 there were 28,809 IPD episodes in 28,218 individuals. A total of 512 (1.8%) persons experienced 591 recurrent episodes. From 2001 to 2016 the incidence of recurrent IPD was 216.2 per 100,000 person-years, 27 times greater than the population rate of primary IPD during this period (8.0 per 100,000 population per year). Between 2011 and 2016, more than one-quarter of individuals experiencing recurrence had no IPD risk factors identified at first episode. ConclusionsThere is substantially increased risk of recurrent IPD after an initial episode. At least one-quarter of those with recurrent episodes have no identified risk factors at the initial episode. Given the potential preventability of future episodes, those with a previous IPD episode should be identified as a high-risk group and receive pneumococcal vaccination.

Dynamics of Invasive Pneumococcal Disease in Israel in Children and Adults in the 13-Valent Pneumococcal Conjugate Vaccine (PCV13) Era: A Nationwide Prospective Surveillance.

Following 13-valent pneumococcal conjugate vaccine (PCV13) implementation in infants worldwide, overall and vaccine-type invasive pneumococcal disease (IPD) rates declined in children, with variable indirect impact on adults. A population-based, prospective, nationwide active surveillance of IPD in Israel, 2004-2019 (for adults ≥18 years, 2009-2019). The 7-valent PCV (PCV7)/PCV13 were implemented in Israel in July 2009/November 2010, respectively, with >90% uptake in children <2 years. The 23-valent pneumococcal polysaccharide vaccine (PPV-23) uptake among those >65 years was ~75%. For pre-PCV episodes with missing serotype, extrapolations were applied. Overall, PCV13 serotypes (VT13) and non-VT13 (NVT) incidence rate ratios (IRRs) comparing pre-PCV (2004-2008), early-PCV (2009-2011), and late-PCV13 (2016-2019) periods were calculated for different age groups. Overall, 8614 IPD cases were recorded. IPD rates declined by 67% in children <5 and 5-17 years, comparing late-PCV13 versus pre-PCV periods (IRR [95% CI]: .33 [.27-.40] and .33 [.21-.50], respectively). For adults, comparing late-PCV13 with early-PCV periods, rates significantly declined by 53% in those aged 18-44, while rates did not decline significantly in other age groups. VT13 rates significantly declined in all ages, with decline rates ranging between 94% in children <5 years and 60% in adults ≥85 years. NVT rates significantly increased in <5-, 50-64-, and ≥65-year age groups. In the late-PCV13 period, serotypes 3, 14, and 19A remained the predominant VT13, while serotypes 8 and 12F emerged as predominant NVTs. Continuous monitoring of circulating serotypes in all ages demonstrated direct and indirect PCV effects, which are essential for the development of new vaccination strategies.

Epidemiology of bacteremia in a pediatric population – A 10-year study

IntroductionWith the widespread introduction of conjugate meningococcal and pneumococcal vaccines, the prevalence and etiology of invasive bacterial infections have changed. We aimed to review all cases of bacteremia in a level II pediatric department over a ten-year period in the post-pneumococcal conjugate vaccine era. MethodsWe reviewed all positive blood cultures (BC) obtained in our department between 2007 and 2016. Results were classified as contaminants, potential pathogens or confirmed pathogens, based on species, number of positive BC in the episode and the patients’ medical history. Demographic and clinical data were collected for patients with identified pathogens. ResultsA total of 638 positive BC were identified (6.6% of total BC); 120 (1.2%) were considered to represent true bacteremia. The most frequently identified microorganism was Streptococcus pneumoniae (29.2%), with a decrease in the number of cases between 2008 and 2015. Staphylococcus aureus was the second most common organism (19.2%) being 21.7% of these methicillin-resistant. Escherichia coli was the most common isolate in children aged less than three months. ConclusionWe found a rate of true bacteremia in children similar to recent studies. Although Streptococcus pneumoniae remains the most common microorganism, its prevalence may be declining. Monitoring microbiological data in children has implications in practice, particularly in local antibiotic prescription.

Nasopharyngeal carriage, serotype pattern and antimicrobial non-susceptibilities of Streptococcus pneumoniae among healthy children in the 13-valent pneumococcal conjugate vaccine era in Barbados, one of the Caribbean countries

BackgroundBarbados like other countries in the English-speaking Caribbean introduced the 7-valent pneumococcal conjugate vaccine (PCV7) in late 2007, replaced by the 13-valent vaccine (PCV13) in 2013, using a 3+ 0 dosing schedule. We investigated the prevalence and serotype pattern of nasopharyngeal (NP) carriage of Streptococcus pneumoniae (SP) and the Antimicrobial Non-susceptibility of SP (ANSP) among children. Materials and methodsA cross sectional survey of NP carriage. NP swabs were collected from healthy children (6 months to 10 years) attending the well-child clinic at the polyclinics, after parental consent, during 2016–2017. Samples were cultured for SP and isolates were serotyped by the capsular swelling method using commercial group- and type-specific sera. Susceptibility testing was conducted by broth microdilution MIC determination, according to CLSI recommended breakpoints. ResultsPrevalence of NP carriage of SP among 198 healthy children, 88.9% immunized for PCV, was 12.6% (95% CI=8.5%, 18.3%). Prevalence of NP carriage for the VT and NVT was 7.1% (95% CI=4.1%, 11.8%) and 5.6% (95%CI=3.0%, 10.0%) respectively. Serotype 19F was the most common NP isolate in 7 (28%; 12.9%, 49.6%) children and this was followed by 15B/C (25%), 35B (12%) and 6B (12.5%). More than 50% of isolates exhibited Antimicrobial Non-sensitive SP (ANSP) to Penicillin (Oral), Azithromycin and Co-trimoxazole. Serotypes 19F, 19A and 23F showed high level ANSP to 10/11 commonly used antibiotics. ConclusionsNP carriage of SP among healthy children immunized with PCV continues to be predominantly VT and exhibit high ANSP.

Clonal lineages and antimicrobial resistance of nonencapsulated Streptococcus pneumoniae in the post-pneumococcal conjugate vaccine era in Japan

ObjectivesThe emergence and spread of nonencapsulated Streptococcus pneumoniae (NESp) is a public health concern in the post-pneumococcal conjugate vaccine era. We analyzed the prevalence, molecular characteristics, and antimicrobial resistance of NESp responsible for noninvasive infections in northern Japan. MethodsNESp isolates were identified using molecular and phenotypical methods among 4463 S. pneumoniae isolates from noninvasive infection cases during 4 study periods between January 2011 and January 2019. NESp isolates were analyzed for antimicrobial susceptibility, genotype, and virulence-associated genes. ResultsSeventy-one NESp isolates were identified (1.6% of total clinical isolates) and assigned to the null capsule clade (NCC)1 (pspK+) (94.4%) or NCC2 (aliC+/aliD+) (5.6%). The dominant sequence types (STs) were ST7502 (23.9%), ST4845 (19.7%), ST16214 (11.3%), ST11379 (9.9%), and ST7786 (7.0%). These 5 dominant STs and all 7 novel STs were related to the sporadic NESp lineage ST1106 or PMEN clone Denmark14-ST230. High non-susceptibility rates of NESp were observed for trimethoprim-sulfamethoxazole, erythromycin, and tetracycline (>92.9%), and multidrug resistance was observed in 88.7% of the NESp isolates, including all ST7502, ST4845, and ST11379 isolates. ConclusionsThe study revealed that the dominant clonal groups of NESp were associated with a high prevalence of non-susceptibility to antimicrobials in northern Japan.

Necrotizing pneumonia among Italian children in the pneumococcal conjugate vaccine era.

Necrotizing pneumonia (NP) is a severe complication of community-acquired pneumonia. The impact of 13-valent pneumococcal conjugate vaccine (PCV13) on the epidemiology of NP in children has not been assessed. Medical records of children less than 18 years admitted with NP to two pediatric hospitals in Italy between 2005 and 2019 were reviewed. The following four periods were defined: 2005-2010 (pre-PCV13), 2011-2013 (early post-PCV13), 2014-2016 (intermediate post-PCV13), and 2017-2019 (late post-PCV13). Forty-three children (median age, 44 months) were included. Most of them (93%) were previously healthy. No differences in age, sex, season of admission, comorbidity, clinical presentation, or hospital course were identified between pre-PCV13 and post-PCV13 periods. A significant decrease in the rate of NP-associated hospitalizations was found between the early (1.5/1000 admissions/year) and the intermediate (0.35/1000 admissions/year) post-PCV13 period (p = .001). An increased trend in admissions was found thereafter. Streptococcus pneumoniae was the most common agent detected in both periods (pre-PCV13: 11/18, 61%; post-PCV13: 13/25, 52%). Serotype 3 was the most common strain in both periods (pre-PCV13: 3/11, 27%; post-PCV13; 4/13, 31%). There were no changes in the etiology over time, but most patients with Streptococcus pyogenes or Staphylococcus aureus infection were admitted during the post-PCV13 period. The hospitalization rate for NP in children decreased a few years after the implementation of PCV13 immunization in Italy. However, an increased trend in admissions was found thereafter. S. pneumoniae was the most frequent causal agent in both pre- and post-PCV13 periods. Pneumococcal serotypes were mainly represented by Strain 3.

An affordable pneumococcal conjugate vaccine after 20 years

An affordable pneumococcal conjugate vaccine after 20 years

Pneumococcal serotypes causing pneumonia in the 13 valent pneumococcal conjugate vaccine era in Australian children

Pneumococcal serotypes causing pneumonia in the 13 valent pneumococcal conjugate vaccine era in Australian children

Nationwide Trends of Invasive Pneumococcal Disease in Spain From 2009 Through 2019 in Children and Adults During the Pneumococcal Conjugate Vaccine Era.

Introduction of pneumococcal conjugate vaccines (PCVs) has reduced the disease caused by vaccine serotypes in children, providing herd protection to adults. However, the emergence of nonvaccine serotypes is of great concern worldwide. This study includes national laboratory data from invasive pneumococcal disease (IPD) cases that affected pediatric and adult populations during 2009-2019. The impact of implementing different vaccine strategies for immunocompetent adults by comparing Spanish regions that used the 13-valent PCV (PCV13) vs regions that used the 23-valent pneumococcal polysaccharide vaccine (PPV23) was also analyzed for 2017-2019. The overall reductions in IPD cases by PCV13 serotypes in children and adults were 88% and 59%, respectively, during 2009-2019, with a constant increase in serotype 8 in adults since 2015. IPD cases by additional serotypes covered by PPV23 increased from 20% in 2009 to 52% in 2019. In children, serotype 24F was the most frequent in 2019, whereas serotypes 3 and 8 accounted for 36% of IPD cases in adults. Introduction of PCV13 or PPV23 in the adult calendar of certain Spanish regions reduced the IPD cases by PCV13 serotypes by up to 25% and 11%, respectively, showing a decrease of serotype 3 when PCV13 was used. Use of PCV13 in children has affected the epidemiology, reducing the burden of IPD in children but also in adults by herd protection; however, the increase in serotype 8 in adults is worrisome. Vaccination with PCV13 in adults seems to control IPD cases by PCV13 serotypes including serotype 3.

Pneumococcal Meningitis Among Children in the Post-13-Valent Pneumococcal Conjugate Vaccine Era: Three Case Reports

We report three cases under two years of age, of meningitis due to Streptococcus pneumoniae in vaccinated children. Two grew non-typable strain and the third serotype 10A. All improved with no neurological sequel. Continued monitoring of the epidemiology of bacterial meningitis within the post13-valent pneumococcal conjugate vaccine introduction is warranted.

Isolating polysaccharide IgG pneumococcal antibody responses by pre-adsorption of conjugate vaccine serotypes: A modified approach for the conjugate vaccine era

BackgroundAssessment of pure polysaccharide response to the 23-valent pneumococcal polysaccharide vaccine (PPV23) can be biased by previous exposure to the conjugate vaccine (PCV). We applied pre-analytical modification to the existing ELISA by pre-incubating serum with PCV. MethodsPCV-adsorbed and non-adsorbed sera were prepared before measuring the concentration of anti-pneumococcal capsular polysaccharide (PCP) IgG antibodies by the whole pneumococcal ELISA. Paired pre and post-pneumococcal vaccination sera from 73 subjects were analyzed and the baseline anti-PCP IgG for each sample was subtracted from the post-vaccination value to measure vaccine responses. Absolute change in titers and fold changes were then compared between both methods. ResultsIn the PCV-vaccinated group (n = 28), pre-adsorption with PCV significantly reduced the vaccine responses compared to non-adsorbed sera [median increase in anti-PCP titers: 27.55 mg/l and 45.98 mg/l, respectively]. In addition, the median fold change dropped significantly from 3.026 to 2.313. In PPV23-vaccinated immunocompetent subjects (n = 28) there was a significant difference in anti-PCP responses with PCV adsorption [median values: 73.71 mg/l without and 51.04 mg/l with adsorption]. All the antibody deficiency patients (n = 17) displayed poor PPV23 responses. Although PPV23 responsiveness was not statistically different between both methods, we have observed a trend for lower anti-PCP IgG titers in PCV-adsorbed sera compared to non-adsorbed ones. Serotype-specific IgG analysis using a multiplexed bead-based immunoassay performed on 10 paired samples confirmed that the adsorption observed is specific to PCV serotypes. ConclusionPre-analytical modification to the conventional ELISA by removing the PCV-specific serotypes may differentiate true polysaccharide response from recall response induced by previous PCV vaccination.

Virulence-Associated Characteristics of Serotype 14 and Serogroup 9 Streptococcus pneumoniae Clones Circulating in Brazil: Association of Penicillin Non-susceptibility With Transparent Colony Phenotype Variants.

Streptococcus pneumoniae remains a major agent of invasive diseases, especially in children and the elderly. The presence of pneumococcal capsule, pneumococcal surface protein A (PspA), and pilus type 1 (PI-1) and the ability of colony phase variation are assumed to play important roles in the virulence potential of this microorganism. Differences in the capsular polysaccharide allow the characterization of more than 90 pneumococcal serotypes; among them, serotype 14 and serogroup 9 stand out due to their prevalence in the pre- pneumococcal conjugate vaccine era and frequent association with penicillin non-susceptibility. Here we investigated the distribution of PI-1 and pspA genes and colony phase variants among 315 S. pneumoniae isolates belonging to serotype 14 and serogroup 9, recovered over 20 years in Brazil, and correlated these characteristics with penicillin susceptibility and genotype as determined by multilocus sequence typing. All strains were shown to carry pspA genes, with those of family 2 (pspA2) being the most common, and nearly half of the strains harbored P1-1 genes. The pspA gene family and the presence of PI-1 genes were conserved features among strains belonging to a given clone. A trend for increasing the occurrence of pspA2 and PI-1 genes over the period of investigation was observed, and it coincided with the dissemination of CC156 (Spain9V-3) clone in Brazil, suggesting a role for these virulence attributes in the establishment and the persistence of this successful clone. Opaque variant was the colony phenotype most frequently observed, regardless of clonal type. On the other hand, the transparent variant was more commonly associated with penicillin-non-susceptible pneumococci and with strains presenting evidence of recombination events involving the genes coding for polysaccharide capsule and PspA, suggesting that pneumococcal transparent variants may present a higher ability to acquire exogenous DNA. The results bring to light new information about the virulence potentials of serotype 14 and serogroup 9 S. pneumoniae isolates representing the major clones that have been associated with the emergence and the dissemination of antimicrobial resistance in our setting since the late 1980s.