Changes in Invasive Pneumococcal Disease Caused by Streptococcus pneumoniae Serotype 1 following Introduction of PCV10 and PCV13: Findings from the PSERENADE Project

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04-0.06) for all ages, 0.05 (0.04-0.05) for <5 years of age, 0.08 (0.06-0.09) for 5-17 years, 0.06 (0.05-0.08) for 18-49 years, 0.06 (0.05-0.07) for 50-64 years, and 0.05 (0.04-0.06) for ≥65 years. PCV10/13 use in infant immunization programs was followed by a 95% reduction in ST1 IPD in all ages after approximately 6 years. Limited data availability from the highest ST1 disease burden countries using a 3+0 schedule constrains generalizability and data from these settings are needed

Global Landscape Review of Serotype-Specific Invasive Pneumococcal Disease Surveillance among Countries Using PCV10/13: The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) Project.

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon

Invasive Pneumococcal Infection in a Healthy Infant Caused by Two Different Serotypes

We present a case of invasive pneumococcal infection in a healthy 10-month-old infant from whom Streptococcus pneumoniae serotype 23F was isolated from the blood and serotype 23B was isolated from the cerebrospinal fluid. Both serotypes were penicillin nonsusceptible. Pulsed-field gel electrophoresis analysis demonstrated that the two serotypes had distinct DNA patterns, indicating that infection did not occur as a result of capsular transformation but as a result of a mixed infection with two distinct pneumococcal serotypes

Prevalência de sorotipos e resistência antimicrobiana de cepas invasivas do Streptococcus pneumoniae

OBJETIVO: Avaliar o perfil de sorotipos e a susceptibilidade aos antimicrobianos de cepas de Streptococcus pneumoniae obtidas em espécimes clínicos de pacientes com doença invasiva, bem como suas implicações na formulação de vacinas pneumocócicas. MÉTODOS: Cepas de pneumococo isoladas no Laboratório de Análises Clínicas do Hospital de Clínicas da Universidade Federal de Uberlândia a partir de amostras clínicas de pacientes com doença invasiva foram identificadas e enviadas ao Instituto Adolfo Lutz em São Paulo para confirmação da identificação, sorotipagem e determinação da susceptibilidade aos antimicrobianos. RESULTADOS: De abril de 1999 a março de 2003, foram isoladas 148 cepas invasivas de pneumococo, sendo 84 (56,7%) provenientes de pacientes do sexo masculino. A idade variou de um dia a 88,83 anos, com média de 21,33+25,82 anos e mediana de 4,42 anos. Os diagnósticos clínicos mais comuns foram pneumonia (91 casos; 61,4%), meningite (32 casos; 21,6%) e bacteremia sem foco evidente (15 casos; 10,1%). As principais fontes de recuperação foram sangue (76 amostras; 51,3%), líquido pleural (39; 26,3%) e liquor (30; 20,2%). No total, foram identificados 23 diferentes sorotipos entre 143 amostras testadas, sendo os mais comuns os seguintes: 14, 3, 1, 5, 6A, 6B e 18C. Dentre 30 (20,2%) cepas oxacilina-resistentes, 23 (15,5%) confirmaram a resistência à penicilina (12,8% com nível intermediário e 2,7%, com nível pleno), que esteve restrita aos sorotipos 14, 23F, 19A e 6B, predominando em indivíduos com até dois anos de idade (p = 0,0008). Foi detectada susceptibilidade diminuída ao cotrimoxazol (63,4%), à eritromicina (8,3%), à clindamicina (8,7%) e à ofloxacina (0,8%). A resistência à cefotaxima foi detectada em três das 30 cepas testadas (2% das 148), todas elas com resistência confirmada à penicilina. Não foi observada resistência a cloranfenicol, rifampicina ou vancomicina. CONCLUSÕES: A resistência à penicilina foi detectada em 15,5% das cepas e predominou em crianças abaixo de dois anos de idade. Foram identificados 23 diferentes sorotipos de Streptococcus pneumoniae em pacientes internados com doença invasiva, e a maioria dos sorotipos (82,6%) e das cepas (90,2%) está incluída na vacina polissacarídica 23-valente. As cifras para a vacina 7-valente, atualmente disponível (PN CRM7), são de 46,7% dos sorotipos e 63,6% das cepas, obtidos de crianças com até cinco anos de idade

Genetic Diversity of PspA Types among Nasopharyngeal Isolates Collected during an Ongoing Surveillance Study of Children in Brazil

Pneumococcal surface protein A (PspA) has been considered a potential candidate for human vaccines because of its serotype-independent protective immunity. Nasopharyngeal (NP) pneumococcal colonization is highly prevalent in infants and precedes the invasive disease. Thus, prevention of NP colonization may reduce the burden of pneumococcal disease in children. Scarce information focusing on PspA from pneumococcal carriage in humans is available. We examined the genetic diversity of PspA from NP isolates obtained during an ongoing pneumococcal surveillance study with children. PspA families and clades of 183 community-acquired Streptococcus pneumoniae NP isolates from healthy children (n = 97) and children with respiratory tract infections (n = 48), pneumonia (n = 33), or meningitis (n = 5) were investigated. Overall, 79.8% (n = 146) of the pneumococcal isolates were classified as PspA family 1 (35.5%) and family 2 (44.3%), whereas 20.2% of the isolates could not be typed. The distribution of PspA families and clades did not differ significantly according to the clinical status of the children. A dendrogram comparing the genetic relationship between the amino acid sequences of the clade-defining region of PspA from NP strains together with 24 invasive reference strains (GenBank) closely reproduced the profile of the families and clades previously reported for pneumococcal invasive strains. These findings strengthen the idea that the use of PspA as a vaccine antigen may protect children against carriage as well as invasive pneumococcal disease

Discovery of a New Capsular Serotype (6C) within Serogroup 6 of Streptococcus pneumoniae

Using two monoclonal antibodies, we found subtypes among pneumococcal isolates that are typed as serotype 6A by the quellung reaction. The prevalent subtype bound to both monoclonal antibodies and was labeled here 6Aα, whereas the minor subtype bound to only one monoclonal antibody and was labeled 6Aβ. To determine the biochemical nature of the two serologically defined subtypes, we purified capsular polysaccharides (PSs) from the two subtypes and examined their chemical structures with gas-liquid chromatography and mass spectrometry. The study results for 6Aα PS are consistent with the previously published structure of 6A PS, which is →2) galactose (1→3) glucose (1→3) rhamnose (1→3) ribitol (5→phosphate. In contrast, the 6Aβ PS study results show that its repeating unit is →2) glucose 1 (1→3) glucose 2 (1→3) rhamnose (1→3) ribitol (5→phosphate. We propose to continue referring to 6Aα as serotype 6A but to refer to 6Aβ as serotype 6C. Serotype 6C would thus represent the 91st pneumococcal serotype, with 90 pneumococcal serotypes having previously been recognized. This study also demonstrates that a new serotype may exist within an established and well-characterized serogroup or serotype

Genetic Relationship between Streptococcus pneumoniae Isolates from Nasopharyngeal and Cerebrospinal Fluid of Two Infants with Pneumococcal Meningitis

The molecular epidemiology of Streptococcus pneumoniae isolates from carriage and cerebrospinal fluid (CSF) concurrently recovered from the same individual has not yet been reported. By using pulsed-field gel electrophoresis, we demonstrated the genetic linkage among strains from CSF and nasopharynges of two children with pneumococcal meningitis

Evaluation of Methodology for Serotyping Invasive and Nasopharyngeal Isolates of Haemophilus influenzae in the Ongoing Surveillance in Brazil

To assess the magnitude of discrepant results obtained by routine Haemophilus influenzae serotyping, 258 isolates, collected by the epidemiological surveillance system in Brazil from individuals with invasive diseases or carriage, were evaluated by two slide agglutination (SlAg) methods: SlAg method 1, by which strains were initially screened with a serotype b-specific antiserum, and SlAg method 2, by which strains were tested against all serotype-specific antisera in parallel. Investigators comparing results of the two SlAg methods with those obtained by capsule type-specific PCR were blinded to the method used. The serotype prevalence rates found by the three methods were significantly different, involving discrepancies mainly between serotype b and noncapsulated (NC) isolates. For invasive isolates (n = 131), the overall agreement rate between SlAg method 1 or 2 and PCR was 68.0 or 88.3%, respectively, whereas for colonizing isolates (n = 127) the corresponding rate was 46.5 or 94.2%, respectively. SlAg method 2 improved the ascertainment of serotypes over that obtained with SlAg method 1, demonstrating good correlation with PCR. Use of the polyvalent antiserum as a screening reagent for SlAg for invasive and colonizing isolates showed poor discriminatory power, with a sensitivity of 65.8% and a specificity of 91.7%. We stress the importance of using a well-standardized SlAg methodology and suggest that reference laboratories should utilize PCR routinely to confirm SlAg results and to check all nonspecific SlAg reactions and apparent NC isolates by SlAg in order to provide reliable data on the prevalence of H. influenzae serotypes in the H. influenzae type b vaccine era