Maria Cristina de Cunto Brandileone

Effectiveness of ten-valent pneumococcal conjugate vaccine against invasive pneumococcal disease in Brazil: a matched case-control study

BACKGROUND In March 2010, Brazil introduced the ten-valent pneumococcal conjugate vaccine (PCV10), which was licensed based on non-inferiority of immunological correlates of protection compared with the seven-valent vaccine. The schedule comprised three primary doses at ages 2 months, 4 months, and 6 months, and a booster dose at age 12 months. A single catch-up dose was offered for children aged 12-23 months at the time of introduction. We assessed PCV10 effectiveness against invasive pneumococcal disease in Brazilian children. METHODS Invasive pneumococcal disease, defined as isolation of Streptococcus pneumoniae from blood, cerebrospinal fluid, or another normally sterile site, was identified in children age-eligible for at least one PCV10 dose through laboratory-based and hospital-based surveillance in ten states in Brazil from March 1, 2010, until Dec 31, 2012. We aimed to identify four age-matched and neighbourhood-matched controls for each case. We used conditional logistic regression and calculated PCV10 effectiveness as (1-adjusted matched odds ratio) × 100% for vaccine-type and vaccine-related serotypes (ie, in the same serogroup as a vaccine serotype). FINDINGS In 316 cases (median age 13·2 months, range 2·6-53·1) and 1219 controls (13·3 months, 2·6-53·1), the adjusted effectiveness of an age-appropriate PCV10 schedule was 83·8% (95% CI 65·9-92·3) against vaccine serotypes, and 77·9% (41·0-91·7) against vaccine-related serotypes. Serotype-specific effectiveness was shown for the two most common vaccine serotypes-14 (87·7%, 60·8-96·1) and 6B (82·8%, 23·8-96·1)-and serotype 19A (82·2%, 10·7-96·4), a serotype related to vaccine serotype 19F. A single catch-up dose in children aged 12-23 months was effective against vaccine-type disease (68·0%, 17·6-87·6). No significant effectiveness was shown against non-vaccine serotypes for age-appropriate or catch-up schedules. INTERPRETATION In the routine immunisation programme in Brazil, PCV10 prevents invasive disease caused by vaccine serotypes. PCV10 might provide cross-protection against some vaccine-related serotypes. FUNDING Brazilian Ministry of Health, Pan-American Health Organization, and US Centers for Disease Control and Prevention.

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

ABSTRACT 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.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America, Sireva-Vigía Group, 1993 to 1999

BACKGROUND Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. METHODS The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. RESULTS By June, 1999, 4,105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. CONCLUSION These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.Background. Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. Methods. The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. Results. By June, 1999, 4105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. Conclusion. These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

Prevention of Haemophilus influenzae Type b (Hib) Meningitis and Emergence of Serotype Replacement with Type a Strains after Introduction of Hib Immunization in Brazil

Surveillance for Haemophilus influenzae meningitis cases was performed in Salvador, Brazil, before and after introduction of H. influenzae type b (Hib) immunization. The incidence of Hib meningitis decreased 69% during the 1-year period after initiation of Hib immunization (from 2.62 to 0.81 cases/100,000 person-years; P<.001). In contrast, the incidence for H. influenzae type a meningitis increased 8-fold (from 0.02 to 0.16 cases/100,000 person-years; P=.008). Pulsed-field gel electrophoretic analysis demonstrated that H. influenzae type a isolates belonged to 2 clonally related groups, both of which were found before Hib immunization commenced. Therefore, Hib immunization contributed to an increased risk for H. influenzae type a meningitis through selection of circulating H. influenzae type a clones. The risk attributable to serotype replacement is small in comparison to the large reduction in Hib meningitis due to immunization. However, these findings highlight the need to maintain surveillance as the use of conjugate vaccines expands worldwide.

Invasive Streptococcus pneumoniae Infection in Latin American Children: Results of the Pan American Health Organization Surveillance Study

Protein-polysaccharide conjugate vaccines against Streptococcus pneumoniae promise to be an effective public health intervention for children, especially in an era of increasing antimicrobial resistance. To characterize the distribution of capsular types in Latin America, surveillance for invasive pneumococcal infection in children < or = 5 years of age was done in six countries between February 1993 and April 1996. Fifty percent of 1,649 sterile-site isolates were from children with pneumonia, and 52% were isolated from blood. The 15 most common of the capsular types prevalent throughout the region accounted for 87.7% of all isolates. Overall, 24.9% of isolates had diminished susceptibility to penicillin: 16.7% had intermediate resistance and 8.3% had high-level resistance. Three customized vaccine formulas containing 7, 12, and 15 capsular types were found to have regional coverages of 72%, 85%, and 88%, respectively. This study emphasizes the need for local surveillance for invasive pneumococcal disease prior to the development and evaluation of protein-polysaccharide conjugate vaccines for children.

Laboratory-based surveillance of Streptococcus pneumoniae invasive disease in children in 10 Latin American countries: a SIREVA II project, 2000-2005.

Background: For the last 14 years the Pan American Health Organization has been promoting surveillance of invasive pneumococcal disease in Latin American children for better understanding of the disease tendencies regarding capsular types circulation in each country and susceptibility to antimicrobials. Methods: Laboratory-based surveillance data from 10 Latin American countries collected from 2000 to 2005 were analyzed, including serotype distribution and susceptibility to beta-lactam antibiotics. Results: Although 61 different capsular types were identified during the 6-year surveillance, 13 serotypes accounted for 86% of all isolates. These were consistently the most prevalent throughout the study period with serotype 14 predominating. Diminished susceptibility to penicillin was detected in 38% of all Streptococcus pneumoniae isolates, with the highest prevalence in Dominican Republic and Mexico. Decreased susceptibility to penicillin increased in Brazil and Colombia whereas decreased high resistance rates was recorded in Chile. Conclusions: These data indicate that 10 countries of the Region continue to have high quality laboratory-based surveillance for pneumococcal disease thus generating valuable information so that healthcare decision makers may prioritize interventions. The heptavalent vaccine will potentially cover from 52.4% to 76.5% of strains causing invasive pneumococcal disease and the 13 valent from 76.7% to 88.3%.

Penicillin resistant pneumococcus and risk of treatment failure in pneumonia

Objective: To determine whether the presence of in vitro penicillin-resistant Streptococcus pneumoniae increases the risk of clinical failure in children hospitalised with severe pneumonia and treated with penicillin/ampicillin. Design: Multicentre, prospective, observational study. Setting: 12 tertiary-care centres in three countries in Latin America. Patients: 240 children aged 3–59 months, hospitalised with severe pneumonia and known in vitro susceptibility of S pneumoniae. Intervention: Patients were treated with intravenous penicillin/ampicillin after collection of blood and, when possible, pleural fluid for culture. The minimal inhibitory concentration (MIC) test was used to determine penicillin susceptibility of the pneumococcal strains isolated. Children were continuously monitored until discharge. Main outcome measures: The primary outcome was treatment failure (using clinical criteria). Results: Overall treatment failure was 21%. After allowing for different potential confounders, there was no evidence of association between treatment failure and in vitro resistance of S pneumoniae to penicillin according to the Clinical Laboratory Standards Institute (CLSI)/National Committee for Clinical Laboratory Standards (NCCLS) interpretative standards (adjRR = 1.03; 95%CI: 0.49–1.90 for resistant S pneumoniae). Conclusions: Intravenous penicillin/ampicillin remains the drug of choice for treating penicillin-resistant pneumococcal pneumonia in areas where the MIC does not exceed 2 μg/ml.

Caracterización de aislamientos invasivos de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe: SIREVA II, 2000-2005

OBJECTIVES To analyze the phenotypical characteristics and the susceptibility to antibiotics of the circulating strains of Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis circulating in Latin America and the Caribbean from 2000-2005. Potential coverage by conjugate vaccines was evaluated. METHODS Conventional methods were used to study the distribution of the serotypes or serogroups of 17 303 strains of S. pneumoniae, 2 782 strains of H. influenzae, and 6 955 strains of N. meningitidis isolated from cases of pneumonia, meningitis, sepsis, bacteriemias, and other invasive processes. The antimicrobial susceptibilities of the study strains were evaluated. The isolates came from 453 sentinel surveillance sites in 19 countries in Latin America and four in the Caribbean, as part of the SIREVA II (Network Surveillance System for the Bacterial Agents Responsible for Pneumonia and Meningitis) project. RESULTS S. pneumoniae serotype 14 was the most frequently isolated (21.1%), especially in children under 6 years of age (29.1%). The potential coverages by hepta-, nona-, deca-, and trideca-valent antipneumonia conjugate vaccines were 59.0%, 73.4%, 76.5%, and 85.9%, respectively. Of the isolates, 63.3% were sensitive to penicillin. H. influenzae serotype b was present in 72.2% of the isolations from children under 2 years of age, whereas 8.6% produced serotypes a, c, d, e, and f, and 19.2% could not be serotyped. The rate of H. influenzae beta-lactamase-producing strains isolated from children under 2 years of age was 16.3%. The most frequent N. meningitidis serogroups were B (69.0%) and C (25.7%); 65.8% and 99.2% of the strains were susceptible to penicillin and rifampicin, respectively. CONCLUSIONS These results highlight the importance of comprehensive epidemiological surveillance of S. pneumoniae, H. influenzae and N. meningitidis in Latin America and the Caribbean. The great heterogeneity found in the distribution of S. pneumoniae serotypes among the countries studied could reduce immunization coverage. Conducting a specific analysis of each country to adjust the introduction of new conjugate vaccines and determine the best immunization plan is recommended.

Decreased Point Prevalence of Haemophilus influenzae Type b (Hib) Oropharyngeal Colonization by Mass Immunization of Brazilian Children Less Than 5 Years Old with Hib Polyribosylribitol Phosphate Polysaccharide—Tetanus Toxoid Conjugate Vaccine in Combination with Diphtheria-Tetanus Toxoids—Pertussis Vaccine

A protective herd effect has been described after susceptible populations of children are vaccinated with conjugate Haemophilus influenzae type b (Hib). Hib carriage was studied in children aged 6-24 months attending day care centers in two cities in southern Brazil (Curitiba and Porto Alegre). In Curitiba, routine immunization with Hib polyribosylribitol phosphate polysaccharide-tetanus toxoid conjugate vaccine (PRP-T) in combination with diphtheria-tetanus toxoids-pertussis vaccine (PRP-T/DTP) has been offered since September 1996; DTP vaccine alone is routinely given in Porto Alegre. Children in Porto Alegre (n=643) were 8 times less likely to have received adequate Hib vaccination and 4 times more likely to be Hib carriers than children in Curitiba (n=647; i.e., point prevalence of oropharyngeal colonization, 4.8% vs. 1.2%). Point prevalence of carriage with non-type b or other nontypeable Hi was similar in children of both cities. There was a vaccination effect on carriage rates in children who received a primary 3-dose series, independent of the booster dose, suggesting that a booster may be unnecessary to induce population protection.

Phenotypic and genotypic characterization of VanA Enterococcus isolated during the first nosocomial outbreak in Brazil.

We report the phenotypic and genotypic characterization of 50 VanA Enterococcus clinical isolates from infected patients and 97 isolates from colonized patients obtained during a nosocomial outbreak in a single hospital in São Paulo, Brazil during 1998. The identification of strains to the species level by conventional biochemical and phenotypic tests and by multiplex PCR assay had 100% agreement. Both E. faecalis and E. faecium were isolated from patients during this outbreak. The vanA genotype was confirmed by PCR. Antibiotic susceptibility testing showed that E. faecium isolates are generally less susceptible to antibiotics than E. faecalis. By PCR, 24 of 26 VRE strains tested carried the Tn1546 element. Pulsed-field gel electrophoresis identified five distinct patterns for E. faecalis (A, B, C, D, E) and three for E. faecium (M, N, and O). A single PFGE pattern was identified in the majority of strains of each species and does not discriminate between case and carrier isolates.