Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines.

BACKGROUND: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. METHODS: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. CONCLUSION: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others RESULTS: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly. Keywords: Antimicrobial resistance; Chronic diseases; Comorbidity; Invasive pneumococcal diseases; Pneumococcal conjugate vaccine; Pneumococcal serotypes; Pneumococcal vaccine.

Chronic medical conditions associated with invasive pneumococcal diseases in inpatients in teaching hospitals in São Paulo city: Estimating antimicrobial susceptibility and serotype-coverage of pneumococcal vaccines

ABSTRACT Background: Chronic conditions increase the risk of invasive pneumococcal diseases (IPD). Pneumococcal vaccination remarkably reduced IPD morbimortality in vulnerable populations. In Brazil, pneumococcal vaccines are included in the National Immunization Program (PNI): PCV10 for < 2 years-old, and PPV23 for high risk-patients aged ≥ 2 years and institutionalized ≥ 60 years. PCV13 is available in private clinics and recommended in the PNI for individuals with certain underlying conditions. Methods: A retrospective study was performed using clinical data from all inpatients from five hospitals with IPD from 2016 to 2018 and the corresponding data on serotype and antimicrobial-non-susceptibility of pneumococcus. Vaccine-serotype-coverage was estimated. Patients were classified according to presence of comorbidities: healthy, without comorbidities; at-risk, included immunocompetent persons with specific medical conditions; high-risk, with immunocompromising conditions and others Results: 406 IPD cases were evaluated. Among 324 cases with information on medical conditions, children < 5 years were mostly healthy (55.9%), while presence of comorbidity prevailed in adults ≥ 18 years old (> 82.0%). Presence of ≥1 risk condition was reported in ≥ 34.8% of adults. High-risk conditions were more frequent than at-risk in all age groups. Among high-risk comorbidity (n = 211), cancer (28%), HIV/AIDS (25.7%) and hematological diseases (24.5%) were the most frequent. Among at-risk conditions (n = 89), asthma (16.5%) and diabetes (8.1%) were the most frequent. Among 404 isolates, 42.9% belonged to five serotypes: 19A (14.1%), 3 (8.7%), 6C (7.7%), 4 and 8 (6.2% each); 19A and 6C expressed antimicrobial-non-susceptibility. The vaccine-serotype-coverage was: PCV10, 19.1%, PCV13, 43.8%; PCV15, 47.8%; PCV20, 62.9%; PCV21, 65.8%, and PPV23, 67.3%. Information on hospital outcome was available for 283 patients, of which 28.6% died. Mortality was 54.2% for those with meningitis. Conclusion: Vaccine with expanded valence of serotypes is necessary to offer broad prevention to IPD. The present data contribute to pneumococcal vaccination public health policies for vulnerable patients, mainly those with comorbidity and the elderly.

Changes in the incidence of invasive disease due to Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis during the COVID-19 pandemic in 26 countries and territories in the Invasive Respiratory Infection Surveillance Initiative: a prospective analysis of surveillance data.

BACKGROUND: Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. METHODS: In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. FINDINGS: 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62 837 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0·32 [95% CI 0·27-0·37]) and 82% at 8 weeks (0·18 [0·14-0·23]) following the week in which significant changes in population movements were recorded. INTERPRETATION: The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide. FUNDING: Wellcome Trust (UK), Robert Koch Institute (Germany), Federal Ministry of Health (Germany), Pfizer, Merck, Health Protection Surveillance Centre (Ireland), SpID-Net project (Ireland), European Centre for Disease Prevention and Control (European Union), Horizon 2020 (European Commission), Ministry of Health (Poland), National Programme of Antibiotic Protection (Poland), Ministry of Science and Higher Education (Poland), Agencia de Salut Pública de Catalunya (Spain), Sant Joan de Deu Foundation (Spain), Knut and Alice Wallenberg Foundation (Sweden), Swedish Research Council (Sweden), Region Stockholm (Sweden), Federal Office of Public Health of Switzerland (Switzerland), and French Public Health Agency (France).

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.

Dynamics of antimicrobial resistance of Streptococcus pneumoniae following PCV10 introduction in Brazil: Nationwide surveillance from 2007 to 2019.

BACKGROUND: Brazil introduced 10-valent pneumococcal conjugate vaccine (PCV10) into its immunization program in 2010. We assessed antimicrobial susceptibility of Streptococcus pneumoniae (Spn) obtained from a national surveillance system for invasive pneumococcal diseases (IPD) before/after PCV10 introduction. METHODS: Antimicrobial non-susceptible isolates were defined as intermediate or resistant. Minimum inhibitory concentrations (MICs) to penicillin and ceftriaxone were analyzed by year. Antimicrobial susceptibility rates were assessed for each three-year-period using the pre-PCV10-period as reference. Susceptibility of vaccine-types was evaluated for 2017-2019. RESULTS: 11,380 isolates were studied. Spn with penicillin ≥ 0.125 mg/L and ceftriaxone ≥ 1.0 mg/L decreased in the three-years after PCV10 introduction (2011-2013: penicillin, 28.1-22.5%; ceftriaxone, 11.3%-7.6%) versus pre-PCV10-years (2007-2009: penicillin, 33.8-38.1%; ceftriaxone, 17.2%-15.6%). After 2013, the proportion of Spn with those MICs to penicillin and ceftriaxone increased to 39.4% and 19.7% in 2019, respectively. Non-susceptibility to penicillin and ceftriaxone increased in 2014-2016, and again in 2017-2019 especially among children < 5 years with meningitis (penicillin, 53.9%; ceftriaxone, 28.0%); multidrug-resistance reached 25% in 2017-2019. Serotypes 19A, 6C and 23A were most associated with antimicrobial non-susceptibility. CONCLUSIONS: Antimicrobial non-susceptible Spn decreased in the three-years after vaccination but subsequently increased and was associated with non-PCV10-types. Antimicrobial susceptibility surveillance is fundamental for guiding antibiotic therapy policies.

Upper respiratory tract colonization with Streptococcus pneumoniae in adults.

INTRODUCTION: Most of the current evidence regarding pneumococcal upper respiratory colonization in adults suggests that despite high disease burden, carriage prevalence is low. Contemporary studies on adult pneumococcal colonization have largely followed the pediatric approach by which samples are obtained mostly from the nasopharynx and bacterial detection is evaluated by routine culture alone. Recent evidence suggests that the 'pediatric approach' may be insufficient in adults and pneumococcal detection in this population may be improved by longitudinal studies that include samples from additional respiratory sites combined with more extensive laboratory testing. AREAS COVERED: In this article, relevant literature published in peer review journals on adult pneumococcal colonization, epidemiology, detection methods, and recommendations were reviewed. EXPERT OPINION: Respiratory carriage of Streptococcus pneumoniae has been underestimated in adults. Contemporary pneumococcal carriage studies in adults that collect samples from alternative respiratory sites such as the oropharynx, saliva, or nasal wash; are culture-enriched for pneumococcus; and use molecular diagnostic methods designed to target two pneumococcal DNA sequences should enhance pneumococcal detection in the adult respiratory tract. This finding may have implications for the interpretation of dynamics of pneumococcal transmission and vaccination.

Distribution of invasive Streptococcus pneumoniae serotypes before and 5 years after the introduction of 10-valent pneumococcal conjugate vaccine in Brazil.

BACKGROUND: In March 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the routine immunization program in Brazil. We describe the pneumococcal serotypes that caused invasive pneumococcal diseases (IPD) before and after the introduction of PCV10 using data from a national laboratory-based surveillance system. METHOD: We compared the prevalence of vaccine types (VT) and non-vaccine types (NVT) of Streptococcus pneumoniae in three periods, pre-PCV10 (January/2005-December/2009), early post-PCV10 (January/2010-December/2013), and late post-PCV10 (January/2014-December/2015), by episode in meningitis and non-meningitis cases and by age group. Changes in serotype prevalence in the early and late post-PCV10 periods were determined using pre-PCV10 period as a reference. RESULTS: A total of 8971 IPD isolates from patients aged 2 months to 99 years were analyzed. In the late post-PCV10 period, the VT-IPD reduction in the 2-month to 4-year age group was 83.4% for meningitis and 87.4% for non-meningitis cases; in the age groups 5-17 years, 18-64 years, and ≥65 years, VT declined by 56.1%, 54.1%, and 47.4%, respectively, in meningitis cases, and by 60.9%, 47.7%, and 53.4%, respectively, in non-meningitis cases. NVT-IPD increased throughout the study period, driven mainly by serotypes 3, 6C, and 19A, which remained the predominant types causing IPD in the late post-PCV10 period. CONCLUSION: We observed direct and indirect PCV10 protection against IPD caused by VT and a shift in the distribution of serotypes 5 years after the introduction of PCV10. Continued IPD surveillance is needed to evaluate the sustainability of the high prevalence of serotypes 3, 6C, and 19A, which were not included in PCV10.

The current situation of meningococcal disease in Latin America and updated Global Meningococcal Initiative (GMI) recommendations.

The Global Meningococcal Initiative (GMI) was established in 2009 and comprises an international team of scientists, clinicians, and public health officials with expertise in meningococcal disease (MD). Its primary goal is to promote global prevention of MD through education, research, international cooperation, and developing recommendations that include decreasing the burden of severe disease. The group held its first roundtable meeting with experts from Latin American countries in 2011, and subsequently proposed several recommendations to reduce the regional burden of MD. A second roundtable meeting was convened with Latin American representatives in June 2013 to reassess MD epidemiology, vaccination strategies, and unmet needs in the region, as well as to update the earlier recommendations. Special emphasis was placed on the emergence and spread of serogroup W disease in Argentina and Chile, and the control measures put in place in Chile were a particular focus of discussions. The impact of routine meningococcal vaccination programs, notably in Brazil, was also evaluated. There have been considerable improvements in MD surveillance systems and diagnostic techniques in some countries (e.g., Brazil and Chile), but the lack of adequate infrastructure, trained personnel, and equipment/reagents remains a major barrier to progress in resource-poor countries. The Pan American Health Organization's Revolving Fund is likely to play an important role in improving access to meningococcal vaccines in Latin America. Additional innovative approaches are needed to redress the imbalance in expertise and resources between countries, and thereby improve the control of MD. In Latin America, the GMI recommends establishment of a detailed and comprehensive national/regional surveillance system, standardization of laboratory procedures, adoption of a uniform MD case definition, maintaining laboratory-based surveillance, replacement of polysaccharide vaccines with conjugate formulations (wherever possible), monitoring and evaluating implemented vaccination strategies, conducting cost-effectiveness studies, and developing specific recommendations for vaccination of high-risk groups.

Population-based surveillance for invasive pneumococcal disease and pneumonia in infants and young children in Goiânia, Brazil.

BACKGROUND: Streptococcus pneumoniae is the leading cause of vaccine-preventable death in children <5 years of age globally. We determined incidence rates of invasive pneumococcal disease (IPD), clinical and chest X-ray-confirmed pneumonia (CXR+Pn), S. pneumoniae serotype distribution, and antimicrobial susceptibility in children in Goiânia, Brazil. METHODS: Prospective, population-based surveillance was conducted from May 2007 to May 2009 in children 28 days to <36 months of age presenting to all 33 pediatric healthcare services (outpatient departments, emergency rooms, hospitals) in Goiânia. Eligibility criteria were temperature ≥39.0 °C in the previous 24h and/or clinical suspicion of pneumonia or IPD. RESULTS: 14,509 subjects were enrolled. Median age was 14.0 months. S. pneumoniae was detected in 64 samples from 62 subjects: 58 (90.6%) blood; 4 (6.3%) cerebrospinal fluid; and 2 (3.1%) pleural fluid. Incidence rate of IPD (culture- and polymerase chain reaction-positive) for all children aged 28 days to <36 months was 57.5/100,000; overall incidence for culture-positive only was 54.9/100,000. Age stratification of culture-positive-only subjects found the highest rates were, 114.6/100,000 and 69.8/100,000, respectively, for the 6 months to <12 months and 12 months to <24 months age groups. The overall incidence of invasive pneumonia and pneumococcal meningitis was 37.2/100,000 and 5.3/100,000, respectively. The most common IPD serotypes were 14 (45.0%), 6B (13.3%), 18C (6.7%), and 23F (5.0%). Eight isolates (13.3%) were penicillin nonsusceptible. The cumulative percentages of serotypes included in 7-valent, 10-valent, and 13-valent pneumococcal conjugate vaccines were 78.3%, 80.0%, and 88.3%, respectively. The overall incidence of clinical pneumonia and CXR+Pn was, 9598/100,000 and 3428/100,000, respectively. CXR+Pn rates for hospitalized and non-hospitalized subjects were 1751/100,000 and 1677/100,000, respectively. CONCLUSIONS: The burden of IPD and pneumonia is considerable in children in a large Brazilian city, and is seen in hospitalized as well as ambulatory subjects. Vaccination with pneumococcal conjugate vaccines has the potential to decrease this burden.

Antimicrobial susceptibility of Neisseria meningitidis strains isolated from meningitis cases in Brazil from 2006 to 2008.

OBJECTIVE: To analyze the profile of antimicrobial susceptibility of meningococcal disease isolates collected throughout Brazil from 2006 to 2008 and forwarded to the National Reference Laboratory for Meningitis, Institute Adolfo Lutz - São Paulo. MATERIALS AND METHODS: The MIC to penicillin, ampicillin, chloramphenicol, ceftriaxone, ciprofloxacin and rifampicin was determined in a sample of 1096 (55% of the total isolates received) randomly chosen using the broth microdilution procedure. The breakpoints used were those recommended by the European Monitoring Group on Meningococci (EMGM). RESULTS: Decreased susceptibility to penicillin and ampicillin was detected in 13% and 12.9% respectively. All isolates were susceptible to chloramphenicol, ceftriaxone, and ciprofloxacin. Two strains (0.2%) showed high resistance to rifampicin and 0.5% of the isolates displayed intermediate resistance to rifampicin. CONCLUSIONS: The meningococcal strains isolated in Brazil during 2006-2008 were globally susceptible to all antibiotics currently used in treatment or chemoprophylaxis of meningococcal disease in Brazil.

Antimicrobial susceptibility of Neisseria meningitidis strains isolated from meningitis cases in Brazil from 2006 to 2008

Objective To analyze the profile of antimicrobial susceptibility of meningococcal disease isolates collected throughout Brazil from 2006 to 2008 and forwarded to the National Reference Laboratory for Meningitis, Institute Adolfo Lutz - São Paulo. Materials and methods The MIC to penicillin, ampicillin, chloramphenicol, ceftriaxone, ciprofloxacin and rifampicin was determined in a sample of 1096 (55% of the total isolates received) randomly chosen using the broth microdilution procedure. The breakpoints used were those recommended by the European Monitoring Group on Meningococci (EMGM).Results Decreased susceptibility to penicillin and ampicillin was detected in 13% and 12.9% respectively. All isolates were susceptible to chloramphenicol, ceftriaxone, and ciprofloxacin. Two strains (0.2%) showed high resistance to rifampicin and 0.5% of the isolates displayed intermediate resistance to rifampicin. Conclusions The meningococcal strains isolated in Brazil during 2006-2008 were globally susceptible to all antibiotics currently used in treatment or chemoprophylaxis of meningococcal disease in Brazil (AU)

Objetivo Analizar el perfil de susceptibilidad a los antimicrobianos de las cepas de meningococos aisladas de casos de enfermedad meningocócica en Brasil entre 2006 y 2008 y enviadas al Laboratorio Nacional de Referencia para Meningitis, Instituto Adolfo Lutz, São Paulo. Material y métodos Se determinó la CIM a penicilina, ampicilina, cloranfenicol, ceftriaxona, ciprofloxacino y rifampicina, mediante el procedimiento de microdilución seriada en caldo en una muestra de 1.096 aislados (55% de los aislados recibidos) escogida al azar. Los puntos de corte utilizados fueron los recomendados por el European Monitoring Group on Meningococci (EMGM).Resultados Se detectó disminución de la susceptibilidad a la penicilina y la ampicilina en el 13 y el 12,9% respectivamente. Todos los aislados fueron susceptibles a cloranfenicol, ceftriaxona y ciprofloxacino. Dos cepas (0,2%) mostraron alta resistencia a la rifampicina y el 0,5% de los aislados presentaron resistencia intermedia a la rifampicina. Conclusiones Las cepas de meningococos aisladas en Brasil en el periodo 2006-2008 fueron globalmente susceptibles a los antibióticos actualmente utilizados en el tratamiento o quimioprofilaxis de enfermedad meningocócica en Brasil (AU)

Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells.

PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.

Selection of family 1 PspA molecules capable of inducing broad-ranging cross-reactivity by complement deposition and opsonophagocytosis by murine peritoneal cells

PspA is one of the most well studied pneumococcal proteins and a promising candidate for a future protein-based anti-pneumococcal vaccine. Nevertheless, its structural and serological variability suggests the inclusion of more than one PspA molecule in order to broaden protection. Since different PspAs exhibit variable levels of cross-reactivity, the selection of the protein combination with the highest coverage potential is an essential step for PspA-based vaccine development. This work investigated the level of cross-reactivity within family 1 PspAs, and established a complement based antibody mediated opsonophagocytic assay for measuring the level of cross-protection. Among a panel of ten family 1 PspA molecules, two of them, one belonging to clade 1 and another from clade 2, induced antibodies capable of enhancing complement deposition and mediating the phagocytic killing by mouse peritoneal macrophages of all pneumococci bearing PspA family 1 strains tested, regardless of their serotype. Therefore, we suggest the inclusion of either one in a PspA-based vaccine, as a representative of family 1. Furthermore, our results suggest that opsonophagocytosis by mouse peritoneal cells can be an efficient means of evaluating the induction of protective immune responses in mice across a large number of strains.

Non-typeable Streptococcus pneumoniae carriage isolates genetically similar to invasive and carriage isolates expressing capsular type 14 in Brazilian infants.

OBJECTIVES: We have recently found a high prevalence of non-typeable pneumococcal isolates (NTPn) circulating in day-care centers in Central Brazil, besides serotype 14 isolates. We therefore examined the genetic relationship among NTPn and serotype 14 from carriage and invasive pneumococcal isolates obtained from children attending emergency rooms enrolled in a population-based surveillance. METHODS: The isolates were characterized by Quellung reaction serotyping, PCR for the presence of pneumolysin and the loci for a capsule gene (cpsA) and the type 14 gene (cps14H) in all NTPn, and by multilocus sequence typing and pulsed field gel electrophoresis. RESULTS: 87.2% of the isolates were clustered into nine clusters. The major cluster included 41 pneumococcal serotype 14 (28 carriage and 13 invasive isolates) and two NTPn related to the global pneumococcal clone Spain(9V)-3. Overall, 95.4% of the NTPn carriage strains were genetically related to carriage or invasive strains expressing serotype 14. A dominant NTPn lineage was found, that grouped 14 pneumococcal strains. Almost half of the multidrug-resistant isolates grouped into the NTPn cluster. CONCLUSION: These findings provide baseline data to assess the impact of the pneumococcal vaccination on the molecular epidemiology of Streptococcus pneumoniae. Changes in frequency of NTPn isolates and also genetic changes should be carefully monitored post vaccination, to detect potential vaccine-escape or replacement disease by capsule switched strains, especially in areas where colonization with NTPn has been frequently observed.

Prevalence and risk factors for nasopharyngeal carriage of Streptococcus pneumoniae among adolescents.

Data on the prevalence of pneumococcal nasopharyngeal carriage and its risk factors among adolescents are scarce. The aim of this study was to provide such information. A cross-sectional, population-based prospective study was conducted. Participants were 1013 adolescents (age range 10-19 years) randomly recruited in 22 public schools. Those schools were randomly chosen among 307 public schools from 11 Sanitary Districts of Salvador, Brazil. Nasopharyngeal samples were assessed by standard procedures to recover and identify Streptococcus pneumoniae. Data on potential risk factors were gathered by confidential interview based on a standardized questionnaire. Pneumococci were recovered from 8.2 % [83/1013, 95 % confidence interval (CI) 6.6-10.0]. By stepwise logistic regression, pneumococcal colonization was independently associated with younger age [odds ratio (OR) 0.85, 95 % CI 0.77-0.94, P=0.001], being male (OR 1.78, 95 % CI 1.11-2.85, P=0.02), exposure to passive smoke in the household (OR 1.76, 95 % CI 1.10-2.79, P=0.02), having an upper respiratory infection during recruitment (OR 2.67, 95 % CI 1.67-4.28, P<0.001) and having a history involving an episode of acute asthma during the last year (OR 2.89, 95 % CI 1.18-7.08, P=0.03). The estimated probability of pneumococcal colonization decreased with age (chi(2) for trend=8.52, P=0.003). These findings provide tools for increasing the use of prevention strategies for pneumococcal diseases, such as pneumococcal vaccination among asthmatic patients and public health measures to stop smoking.

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 ((adj)RR = 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 microg/ml.

Distribution of Streptococcus pneumoniae serotypes in nasopharyngeal carriage and in invasive pneumococcal disease in Sao Paulo, Brazil.

To determine whether serotypes of S. pneumoniae isolated from the nasopharynx (NP) are representative of data from patients with invasive disease, we collected NP swab specimens from children, between 3 months and 5 years and obtained data from 105 children hospitalized with invasive disease. The prevalence of penicillin nonsusceptible strains in the NP carriage and invasive disease group was 16.4% and 17%, respectively, in the first period and 42% and 45% in the second period. The serotypes 23F, 6A, 14 and 19F were the most common in the NP study and 14, 1, 5 and 6B were the most common in invasive infections.

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 6Aalpha, whereas the minor subtype bound to only one monoclonal antibody and was labeled 6Abeta. 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 6Aalpha 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 6Abeta 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 6Aalpha as serotype 6A but to refer to 6Abeta 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.